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Sample records for progenitores siluriformes pimelodidae

  1. Genetic divergence between Pseudoplatystoma corruscans and Pseudoplatystoma reticulatum (Siluriformes: Pimelodidae) in the Paraná River Basin.

    PubMed

    Bignotto, T S; Prioli, A J; Prioli, S M A P; Maniglia, T C; Boni, T A; Lucio, L C; Gomes, V N; Prioli, R A; Oliveira, A V; Júlio, H F; Prioli, L M

    2009-06-01

    Pseudoplatystoma corruscans (Spix and Agassiz, 1829) and Pseudoplatystoma reticulatum (Eingenmann and Eigenmann, 1889) are large migratory catfishes of high biological importance and great commercial value in South America. Because fertile crossbreeds can be artificially produced in hatcheries, a high genetic proximity between these two Pimelodidae species is conceivable. Possible escape of crossbred specimens from pisciculture stations is a serious environmental concern. Despite their importance, knowledge of P. corruscans and P. reticulatum biology, ecology, population diversity and genetics is limited. In the present work, the genetic divergence between P. corruscans and P. reticulatum populations from the Paraná River Basin was analyzed on the basis of polymorphisms in ISSR fragments and in the hypervariable sequence of the mitochondrial DNA (mtDNA) control region. Estimates of intraspecific haplotype (h > 0.5) and nucleotide diversities (pi < 0.01) indicate that P. corruscans and P. reticulatum have survived a historical population decline, followed by a demographic expansion. The interspecific polymorphisms within the mtDNA control region and ISSR fragments were suitable as diagnostic molecular markers and could be used to discriminate the two species. A unique Pseudoplatystoma specimen, captured in the Upper Paraná River Floodplain, was identified by these DNA diagnostic markers as a hybrid P. reticulatum x P. corruscans, which possibly escaped from pisciculture. The integrity of the natural population of P. corruscans in the Upper Paraná River is at risk of genetic introgression or homogenization due to the presence of hybrids and the transposition of P. reticulatum upstream through the Canal da Piracema at Itaipu Dam. Data presented herein improve the understanding of the genetic relatedness between P. corruscans and P. reticulatum and represent potential tools for future programs of conservation and surveillance of genetic introgression events and the

  2. Neotropical Monogenoidea. 57. Revision and phylogenetic position of Scleroductus Jara & Cone, 1989 (Gyrodactylidae), with descriptions of new species from the Guatemalan chulin Rhamdia guatemalensis (Günther) (Siluriformes: Heptapteridae) in Mexico and the barred sorubim Pseudoplatystoma fasciatum (Linnaeus) (Siluriformes: Pimelodidae) in Brazil.

    PubMed

    Kritsky, Delane C; Boeger, Walter A; Mendoza-Franco, Edgar F; Vianna, Rogério T

    2013-01-01

    The diagnosis of Scleroductus Jara & Cone, 1989 (Gyrodactylidae) is amended to include viviparous species having a large spine associated with the ejaculatory duct within the male copulatory organ, two band-like projections originating from the posterior margin of the superficial bar and hooks evenly distributed along the haptoral margins. Two new species of Scleroductus are described from the external surfaces of siluriform fishes of Mexico and Brazil: Scleroductus lyrocleithrum n. sp. from the Guatemalan chulin Rhamdia guatemalensis (Günther) (Heptapteridae) in a cenote on the Yucatan Peninsula, Mexico; and Scleroductus angularis n. sp. from the barred sorubim Pseudoplatystoma fasciatum (Linnaeus) (Pimelodidae) in the Rio Tocantins, Tocantins, Brazil. Scleroductus sp. is recorded from the jundiá Rhamdia quelen (Quoy & Gaimard) (Heptapteridae) in the Iguaçu drainage of southern Brazil. Phylogenetic analyses of 18S rDNA suggest that Scleroductus (represented in the analyses by Scleroductus sp. from R. quelen), Ieredactylus Schelkle, Paladini, Shinn, King, Johnson, van Oosterhout, Mohammed & Cable, 2011 (represented by its type-species) and Gyrodactyloides Bychowsky, 1947 (represented by G. bychowskii Al'bova, 1948) comprise the sister taxon to the remaining viviparous gyrodactylids, with Scleroductus serving as the sister group to Ieredactylus + Gyrodactyloides. The clade containing the three taxa is supported by two putative synapomorphic features: two band-like projections (R1 sclerites) originating from the posterior margin of the superficial bar and a large spine associated with the ejaculatory duct within the male copulatory organ. PMID:23263939

  3. Growth and reproduction aspects of Pimelodus maculatus Lacépède, 1803 (Siluriformes, Pimelodidae) of the Cachoeira Dourada reservoir, state of Goiás and Minas Gerais, Brazil.

    PubMed

    Sabinson, L M; Rodrigues Filho, J L; Peret, A C; Verani, J R

    2014-05-01

    Growth and reproduction parameters of the yellow-mandi, Pimelodus maculatus Lacépède, 1803 (Siluriformes, Pimelodidae), were determined for the Cachoeira Dourada reservoir (GO/MG). The field work occurred throughout February 2007 to January 2008 (with the exception of December 2007). Gill nets with mesh sizes from 1.5 to 10 centimeters were placed in three different areas in the reservoir and were collected 24 hours later. A total of 538 specimens were captured, amongst which 242 were females, 219 were males and 77 could not have their sex determined. Sex ratio differed from 1:1 only during July 2007 and January 2008, with males and females predominating in each of those months. Males occupied the medium length classes (18.9 to 24.3 cm) while females were most abundant in the superior classes (from 27 to 37.8 cm).The growth constant K was statistically equal for males (K=0.1851) and females (K=0.1708), however, females P. maculatus may have a greater investment in reproductive tissue, a fact indicated by the elevated values of Kn and GSI during the summer. Bearing in mind that P. maculatus reproduces in the rainy season, a greater gain in weight is expected during the months before the reproduction season, and that after it occurs the fish loses fat and weight as a consequence of metabolic effort. Still, the absence of juveniles may be an indication that the species did not find in the reservoir the proper conditions for reproduction and growth of its fry. PMID:25166330

  4. Comparative application of direct sequencing, PCR-RFLP, and cytogenetic markers in the genetic characterization of Pimelodus (Siluriformes: Pimelodidae) species: possible implications for fish conservation.

    PubMed

    Ferreira, M; Bressane, K C O; Moresco, A R C; Moreira-Filho, O; Almeida-Toledo, L F; Garcia, C

    2014-01-01

    Pimelodus (Pimelodidae) is a genus comprising a group of South American species with complex taxonomic relationships. Cytogenetics, polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and sequencing data of mitochondrial genes were analyzed to characterize 4 Pimelodus species: P. fur, P. heraldoi, P. maculatus, and Pimelodus sp. All populations presented 2n=56 chromosomes and distinct karyotypic formulae. The heterochromatin distribution pattern and the number and location of 5S and 18S rDNA sites are discussed. The application of PCR-RFLP markers and sequencing of mitochondrial DNA genes provided species-specific haplotypes, which allowed us to differentiate the species studied. The mitochondrial gene sequences presented nucleotide mutations in the restriction sites and throughout the sequences, and they were mostly related to synonymous substitutions in the coded proteins; however, they did not affect the protein and its function. Comparing the data obtained using these 3 methodologies, the existence of a species complex in P. maculatus along the basins studied might be inferred, showing that cytogenetics is an important tool in studies focusing on the conservation or management of both natural and captive populations of these fishes. PMID:25036358

  5. New dactylogyrids (Monogenea) parasitizing the gills of catfishes (Siluriformes) from the Amazon River basin in Peru.

    PubMed

    Mendoza-Franco, Edgar F; Scholz, T

    2009-08-01

    Three dactylogyrid (Monogenea) species are described from the gills of siluriform fishes from the rivers around Iquitos, tributaries of the Amazon River in Peru: Demidospermus centromochli n. sp. from Centromochlus heckelii (de Filippi) (Auchenipteridae) and Demidospermus macropteri n. sp. and Ameloblastella unapi n. sp. from Calophysus macropterus (Lichtenstein) (Pimelodidae). The new species of Demidospermus differ from their congeners in having 2 different hook shapes. Ameloblastella unapi n. sp. differs from the other 3 species of the genus in having anchors with an elongate, straight shaft and a short point that forms a 90 degrees angle, a coiled (counterclockwise) male copulatory organ with 13-14 rings, and a coiled vaginal tube. Based on the present study, Pseudovancleaveus Franca, Issac, Pavanelli, and Takemoto, 2003, is regarded as a junior subjective synonym of Ameloblastella Kritsky, Mendoza-Franco, and Scholz, 2000. The finding of Demidospermus and Ameloblastella spp. on these siluriforms extends our host and geographic knowledge of species of these monogenean genera to Peru. PMID:19215149

  6. Metazoan parasites of Mandi-amarelo Pimelodus maculatus and of Jundiá Rhamdia quelen (Osteichthyes: Siluriformes) of Paraíba do Sul River, Volta Redonda, Rio de Janeiro.

    PubMed

    Venancio, Aline Cristine Pinto; de Aguiar, Gesilene Ribeiro; Lopes, Patrícia da Silva; Alves, Dimitri Ramos

    2010-01-01

    Forty-one specimens of mandi-amarelo Pimelodus maculatus Lacépède, 1803 (Siluriformes: Pimelodidae) and 54 specimens of jundiá Rhamdia quelen (Quoy & Gaimard, 1824) (Siluriformes: Heptapteridae) were collected from the Paraíba do Sul River, Volta Redonda, State of Rio de Janeiro, Brazil between November 2007 and October 2008. These fish underwent necropsy so their infracommunities of metazoan parasites could be studied. The same three species of parasites were collected in the two fish species studied. These were one monogenean, one nematode, and one hirudinean. Cucullanus pinnai (Travassos, Artiga, and Pereira, 1928) (Nematoda: Cucullanidae) and Aphanoblastella sp. (Monogenea: Dactylogyridae) were the dominant species with the highest prevalence in P. maculatus and R. quelen. The parasite species of P. maculatus and R. quelen showed an atypical over-dispersed pattern of distribution. No parasite species showed significant correlation between the body total length of the siluriform hosts and their prevalence and abundance. The parasite species richness showed a mean value of 0.87 ± 0.67 (0-2) and 0.57 ± 0.56 (0-2) in P. maculatus and R. quelen, respectively, and no correlation with the body total length. PMID:20943019

  7. Genetic characterization of the Neotropical catfish Pimelodus maculatus (Pimelodidae, Siluriformes) in the Upper Uruguay River

    PubMed Central

    Ribolli, Josiane; de Melo, Cláudio Manoel Rodrigues; Zaniboni-Filho, Evoy

    2012-01-01

    Freshwater fish present unique challenges when one attempts to understand the factors that determine the structure of their populations. Habitat fragmentation is a leading cause of population decline that threatens ecosystems worldwide. In this study, we investigated the conservation status of genetic variability in the Neotropical catfish (Pimelodus maculatus). Specifically, we examined the structure and genetic diversity of this species in a region of the Upper Uruguay River fragmented by natural barriers and dams. There was no genetic structure among the four sites analyzed, indicating the existence of only one population group. A combination of environmental management and genetic monitoring should be used to minimize the impact of impoundment on panmitic populations of migratory fish species. PMID:23271936

  8. On the type locality of Sorubim trigonocephalus Miranda-Ribeiro, 1920 (Siluriformes: Pimelodidae).

    PubMed

    Ohara, Willian Massaharu; Neuhaus, Emanuel Bruno

    2016-01-01

    Sorubim trigonocephalus was described in 1920 by Alípio de Miranda Ribeiro, based on a single specimen collected in a locality identified as "Porto Velho", during the "Comissão das Linhas Telegráficas Estratégicas de Mato Grosso ao Amazonas" (more commonly known as Rondon Commission). Given that the type locality is Porto Velho, the species has been referred to the Madeira River basin (Lundberg & Littmann, 2003; Littmann, 2007; Eschmeyer et al., 2016). Nevertheless, after its description, no additional specimens were collected in the Madeira basin despite several ichthyological expeditions undertaken to the area (Santos, 1996; Camargo & Giarrizzo, 2007; Rapp Py-Daniel et al., 2007; Perin et al., 2007; Pedroza et al., 2012; Casatti et al., 2013; Queiroz et al., 2013a), some of them including region of Porto Velho (Fowler, 1913; Araújo et al., 2009; Torrente-Vilara et al., 2011; Queiroz et al., 2013b). PMID:27470724

  9. Geographical genetics of Pseudoplatystoma punctifer (Castelnau, 1855) (Siluriformes, Pimelodidae) in the Amazon Basin.

    PubMed

    Telles, M P C; Collevatti, R G; Braga, R S; Guedes, L B S; Castro, T G; Costa, M C; Silva-Júnior, N J; Barthem, R B; Diniz-Filho, J A F

    2014-01-01

    Geographical genetics allows the evaluation of evolutionary processes underlying genetic variation within and among local populations and forms the basis for establishing more effective strategies for biodiversity conservation at the population level. In this study, we used explicit spatial analyses to investigate molecular genetic variation (estimated using 7 microsatellite markers) of Pseudoplatystoma punctifer, by using samples obtained from 15 localities along the Madeira River and Solimões, Amazon Basin. A high genetic diversity was observed associated with a relatively low FST (0.057; P < 0.001), but pairwise FST values ranged from zero up to 0.21 when some pairs of populations were compared. These FST values have a relatively low correlation with geographic distances (r = 0.343; P = 0.074 by Mantel test), but a Mantel correlogram revealed that close populations (up to 80 km) tended to be more similar than expected by chance (r = 0.360; P = 0.015). The correlogram also showed a exponential-like decrease of genetic similarity with distance, with a patch-size of around 200 km, compatible with isolation-by-distance and analogous processes related to local constraints of dispersal and spatially structured levels of gene flow. The pattern revealed herein has important implications for establishing strategies to maintain genetic diversity in the species, especially considering the threats due to human impacts caused by building large dams in this river system. PMID:24854445

  10. Sperm of Doradidae (Teleostei: Siluriformes).

    PubMed

    Quagio-Grassiotto, I; Ortiz, R J; Pérez, M H Sabaj; Oliveira, C

    2011-02-01

    Spermatic characteristics were studied in 10 species representing several distinct groups within the catfish family Doradidae. Interestingly, different types of spermatogenesis, spermiogenesis and spermatozoa are correlated with intrafamilial groups previously proposed for Doradidae. Semi-cystic spermatogenesis, modified Type III spermiogenesis, and biflagellate sperm appear to be unique within Doradidae to the subfamily Astrodoradinae. Other doradid species have sperm with a single flagellum, cystic spermatogenesis, and spermiogenesis of Type I (Pterodoras granulosus, Rhinodoras dorbignyi), Type I modified (Oxydoras kneri), or Type III (Trachydoras paraguayensis). Doradids have an external mode of fertilization, and share a few spermatic characteristics, such as cystic spermatogenesis, Type I spermiogenesis and uniflagellate sperm, with its sister group Auchenipteridae, a family exhibiting sperm modifications associated with insemination and internal fertilization. Semi-cystic spermatogenesis and biflagellate spermatozoa are also found in Aspredinidae, and corroborate recent proposals that Aspredinidae and Doradoidea (Doradidae+Auchenipteridae) are sister groups and that Astrodoradinae occupies a basal position within Doradidae. The co-occurrence in various catfish families of semi-cystic spermatogenesis and either biflagellate spermatozoa (Aspredinidae, Cetopsidae, Doradidae, Malapturidae, Nematogenyidae) or uniflagellate sperm with two axonemes (Ariidae) reinforces the suggestion that such characteristics are correlated. Semi-cystic spermatogenesis and biflagellate sperm may represent ancestral conditions for Loricarioidei and Siluroidei of Siluriformes as they occur in putatively basal members of each suborder, Nematogenyidae and Cetopsidae, respectively. However, if semi-cystic spermatogenesis and biflagellate sperm are ancestral for Siluriformes, cystic spermatogenesis and uniflagellate sperm have arisen independently in multiple lineages including

  11. Genetic structure and historical diversification of catfish Brachyplatystoma platynemum (Siluriformes: Pimelodidae) in the Amazon basin with implications for its conservation

    PubMed Central

    Ochoa, Luz Eneida; Pereira, Luiz Henrique G; Costa-Silva, Guilherme Jose; Roxo, Fábio F; Batista, Jacqueline S; Formiga, Kyara; Foresti, Fausto; Oliveira, Claudio

    2015-01-01

    Brachyplatystoma platynemum is a catfish species widely distributed in the Amazon basin. Despite being considered of little commercial interest, the decline in other fish populations has contributed to the increase in the catches of this species. The structure, population genetic variability, and evolutionary process that have driven the diversification of this species are presently unknown. Considering that, in order to better understand the genetic structure of this species, we analyzed individuals from seven locations of the Amazon basin using eight molecular markers: control region and cytochrome b mtDNA sequences, and a set of six nuclear microsatellite loci. The results show high levels of haplotype diversity and point to the occurrence of two structured populations (Amazon River and the Madeira River) with high values for FST. Divergence time estimates based on mtDNA indicated that these populations diverged about 1.0 Mya (0.2–2.5 Mya 95% HPD) using cytochrome b and 1.4 Mya (0.2–2.7 Mya 95% HPD) using control region. During that time, the influence of climate changes and hydrological events such as sea level oscillations and drainage isolation as a result of geological processes in the Pleistocene may have contributed to the current structure of B. platynemum populations, as well as of differences in water chemistry in Madeira River. The strong genetic structure and the time of genetic divergence estimated for the groups may indicate the existence of strong structure populations of B. platynemum in the Amazon basin. PMID:26045952

  12. Metazoan endoparasites diversity of Pseudoplatystoma corruscans (Siluriformes: Pimelodidae) as an indicator of environmental alterations on a tropical aquatic system.

    PubMed

    Ribeiro, Thamy S; Lizama, Maria A P; Takemoto, Ricardo M

    2014-09-01

    The aim of the present study was to detect the alterations of Pseudoplatystoma corruscans parasite infracommunity structure, after the construction of the Porto Primavera dam on the high Paraná River floodplain. The execution of this research was based on 119 host specimens collected between March 2011 and September 2012, and the results were compared to studies performed on periods before the reservoir's construction, when 110 fishes were collected between March 1992 and February 1993. Five parasite species still remain on the environment, despite the environmental modifications: Choanoscolex abscissus, Spasskyelina spinulifera, Nomimoscolex pertierrae, Harriscolex kaparari and Contracaecum sp 2. The Berger-Parker dominance index, calculated to the parasite fauna of 1992, did not show the dominance of any species, while, on the present days, this same index accused the dominance of Nomimoscolex pertierrae (49%) and Choanoscolex abscissus (50%). The present study reports the disappearance of Megathylacus travassosi, Contracaecum sp. 1, Contracaecum sp. 3, Procamallanus (Spirocamallanus) sp. and Cucullanus pseudoplatystomae, suggesting the possibility of a local extinction or a host switch of these species. It has also been registered an Acanthocephala specimen, a genus not observed on this host yet. The results here presented show that the antropic influences on natural systems alter the environmental conditions, what is reflected on the richness and diversity parasite levels. PMID:25119352

  13. Mitochondrial genome of the Neotropical catfish Ageneiosus pardalis, Lütken 1874 (Siluriformes, Auchenipteridae).

    PubMed

    Restrepo-Escobar, Natalia; Alzate, Juan F; Márquez, Edna J

    2016-05-01

    Ageneiosus pardalis is a trans-Andean member of the Neotropical freshwater fish family Auchenipteridae (Siluriformes). In this work, the complete mitochondrial genome of A. pardalis was pyrosequenced by FLX 454 technology. The mitochondrial genome is 16,484 bp in length and encodes 13 proteins, 22 tRNAs and 2 ribosomal RNAs. Additionally, the synteny is conserved with others species of the Auchenipteridae family as well as other Siluriformes. PMID:25423507

  14. Progenitor Epithelium

    PubMed Central

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  15. The complete mitochondrial genome sequence of Plotosus japonicus (Siluriformes: Plotosidae) and phylogenetic studies of Siluriformes.

    PubMed

    Liu, Yan-Hua; Zhang, Ming-Hai

    2016-07-01

    In this study, we first determined and described the complete mitogenome sequence of Plotosus japonicus, which is a kind of marine fish widely distributed in Northwest Pacific. The complete mitogenome sequence is 16 472 bp in length, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, a putative control region (CR) and a light-strand replication origin (OL). The overall base composition is 31.9% A, 24.7% T, 27.7% C, 15.7% G, with a slight AT bias (56.6%), similar to other vertebrate mitochondrial genomes. All the protein-coding genes use the initiation codon ATG except COI uses GTG. Most of them have TAA or TAG as the stop codon, while COII and ND4 use AGA, COIII and Cytb use an incomplete stop codon TA or T. Maximum Likelihood (ML) tree and Bayesian analyses based on concatenated nucleotide sequences of 12 mitochondrial protein-coding genes were constructed and both yielded identical topologies. These results are expected to provide useful molecular data for species identification and further phylogenetic studies of Siluriformes. PMID:26122342

  16. Cytogenetic characterization of F1, F2 and backcross hybrids of the Neotropical catfish species Pseudoplatystoma corruscans and Pseudoplatystoma reticulatum (Pimelodidae, Siluriformes)

    PubMed Central

    do Prado, Fernanda Dotti; Nunes, Tatiana Leite; Senhorini, José Augusto; Bortolozzi, Jehud; Foresti, Fausto; Porto-Foresti, Fábio

    2012-01-01

    The cytogenetic characteristics of Pseudoplatystoma corruscans and Pseudoplatystoma reticulatum and their F1, F2 and backcross hybrids were assessed by using chromosome banding techniques. The diploid number of 56 chromosomes was constant in all species and lineages, with a karyotypic formula containing 20 metacentric, 12 submetacentric, 12 subtelocentric and 12 acrocentric chromosomes. Nucleolar organizer regions (NORs) were identified in two subtelocentric chromosomes in the parents and hybrids, with partial nucleolar dominance in F1 and F2 specimens. Heterochromatic blocks were detected in the terminal and centromeric regions of some chromosomes in all individuals. For parental and hybrid lineages, 18S ribosomal clusters corresponding to NORs and 5S ribosomal genes were identified in distinct pairs of chromosomes. The striking conservation in the chromosomal macrostructure of the parental species may account for the fertility of their F1 hybrids. Similarly, the lack of marked alterations in the chromosomal structure of the F1 hybrids could account for the maintenance of these features in post-F1 lineages. PMID:22481875

  17. Gonadotropins and Growth Hormone Family Characterization in an Endangered Siluriform Species, Steindachneridion parahybae (Pimelodidae): Relationship With Annual Reproductive Cycle and Induced Spawning in Captivity.

    PubMed

    Honji, Renato Massaaki; Caneppele, Danilo; Pandolfi, Matias; Nostro, Fabiana Laura Lo; Moreira, Renata Guimarães

    2015-09-01

    The aim of this study was to identify and characterize pituitary cells of Steindachneridion parahybae females in captivity, highlighting the possible relationship with reproductive disorders at this level, since this species shows oocyte final maturation, ovulation and spawning dysfunction in captivity. The localization and distribution of growth hormone (GH), prolactin (PRL), somatolactin (SL), β-luteinizing hormone (β-LH), and β-follicle stimulating hormone (β-FSH) immunoreactive (-ir) cells in the adenohypophysis was studied by immunohistochemical and Western blot methods. In addition, cellular morphometric analyses and semi-quantification of ir-cells optical density (OD) during the annual reproductive cycle and after artificial induced spawning (AIS) were performed. Results showed that the distribution and general localization of pituitary cell types were similar to that of other teleost species. However, the morphometrical study of adenohypophysial cells showed differences along the reproductive cycle and following AIS. In general, females at the vitellogenic stage presented greater OD values for GH, PRL and SL than at other maturation stages (previtellogenic and regression stages), probably indicating an increased cellular activity during this stage. Conversely, β-LH OD did not vary during the annual reproductive cycle. After AIS, β-LH, SL and GH ir-cells showed an increase in OD values suggesting a possible involvement on oocyte final maturation, ovulation and spawning or a feedback control on the brain-pituitary-gonads axis. Reproductive dysfunction in S. parahybae females in captivity may be due to alteration of the synthesis pathways of β-LH. In addition, GH family of hormones could modulate associated mechanisms that influence the reproductive status in this species. PMID:25989288

  18. Temporal and spatial distribution of young Brachyplatystoma spp. (Siluriformes: Pimelodidae) along the rapids stretch of the Madeira River (Brazil) before the construction of two hydroelectric dams.

    PubMed

    Cella-Ribeiro, A; Assakawa, L F; Torrente-Vilara, G; Zuanon, J; Leite, R G; Doria, C; Duponchelle, F

    2015-04-01

    Monthly (April 2009 to May 2010) bottom-trawl sampling for Brachyplatystoma species along the rapids stretch of the Madeira River in Brazil revealed that Brachyplatystoma rousseauxii larvae and juveniles were present in low abundances in all areas and during all hydrological periods. The presence of larvae and juveniles throughout the hydrological cycle suggests asynchronous spawning in the headwaters of the Madeira River. PMID:25733151

  19. Trophic ecomorphology of Siluriformes (Pisces, Osteichthyes) from a tropical stream.

    PubMed

    Pagotto, J P A; Goulart, E; Oliveira, E F; Yamamura, C B

    2011-05-01

    The present study analysed the relationship between morphology and trophic structure of Siluriformes (Pisces, Osteichthyes) from the Caracu Stream (22º 45' S and 53º 15' W), a tributary of the Paraná River (Brazil). Sampling was carried out at three sites using electrofishing, and two species of Loricariidae and four of Heptapteridae were obtained. A cluster analysis revealed the presence of three trophic guilds (detritivores, insectivores and omnivores). Principal components analysis demonstrated the segregation of two ecomorphotypes: at one extreme there were the detritivores (Loricariidae) with morphological structures that are fundamental in allowing them to fix themselves to substrates characterised by rushing torrents, thus permitting them to graze on the detritus and organic materials encrusted on the substrate; at the other extreme of the gradient there were the insectivores and omnivores (Heptapteridae), with morphological characteristics that promote superior performance in the exploitation of structurally complex habitats with low current velocity, colonised by insects and plants. Canonical discriminant analysis revealed an ecomorphological divergence between insectivores, which have morphological structures that permit them to capture prey in small spaces among rocks, and omnivores, which have a more compressed body and tend to explore food items deposited in marginal backwater zones. Mantel tests showed that trophic structure was significantly related to the body shape of a species, independently of the phylogenetic history, indicating that, in this case, there was an ecomorphotype for each trophic guild. Therefore, the present study demonstrated that the Siluriformes of the Caracu Stream were ecomorphologically structured and that morphology can be applied as an additional tool in predicting the trophic structure of this group. PMID:21755165

  20. The complete mitochondrial genome sequence of Hemibagrus sp. (Siluriformes: Bagridae).

    PubMed

    Hao, Rong-Chao; Wang, Guo-Hua

    2016-05-01

    At present, the phylogenetic and taxonomic positions of Bagridae and Siluriformes have long been unclear. In this paper, we sequenced and annotated the complete mitogenome of Hemibagrus sp. The total length was 16,529 bp, and was typically consist of 37 genes, including 13 protein-coding genes, 2 rRNAs, 22 tRNA, a light-strand replication origin (OL) and a single large control region (CR). Except for eight tRNA and ND6 genes, all other mitochondrial genes were encoded on the heavy strand (H-strand). The gene content, organization and arrangement were identical to that of a typical bony fish. The overall base composition was 26.5%, 26.8%, 31.7% and 15.0% for T, C, A and G, respectively, with a slight bias on AT content (58.2%). This information could not only contribute to provide useful molecular data for the species identification, but also to further taxonomic and phylogenetic studies of Hemibagrus and Bagridae. PMID:25319292

  1. Blood flukes (Digenea: Aporocotylidae) infecting body cavity of South American catfishes (Siluriformes: Pimelodidae): two new species from rivers in Bolivia, Guyana and Peru with a re-assessment of Plehniella Szidat, 1951.

    PubMed

    Orelis-Ribeiro, Raphael; Bullard, Stephen A

    2015-01-01

    Plehniella Szidat, 1951 is emended based on new collections from South American long-whiskered catfishes. It is clearly differentiated from Sanguinicola Plehn, 1905 by lacking lateral tegumental body spines and by having 6 asymmetrical caeca. Plehniella sabajperezi sp. n. infects body cavity of Pimelodus albofasciatus (Mees) from the Demerara and Rupununi Rivers (Guyana) and Pimelodus blochii (Valenciennes) from Lake Tumi Chucua (Bolivia) and Napo River (Peru). It differs from Plehniella coelomicola Szidat, 1951 (type species) by having a thin-walled vas deferens that greatly exceeds the length of cirrus-sac and that joins the cirrus-sac at level of ovovitelline duct and ootype, an internal seminal vesicle that is absent or diminutive, and a cirrus-sac that is spheroid, nearly marginal, and envelops the laterally-directed distal portion of the male genitalia. Plehniella armbrusteri sp. n. infects body cavity of P. blochii from Lake Tumi Chucua (Bolivia). It differs from P. coelomicola and P. sabajperezi by having a relatively ovoid body, a massive intestine comprising caeca that are deeply-lobed to diverticulate and terminate in the posterior half of the body, a testis that flanks the distal tips of the posteriorly-directed caeca, and a proximal portion of the vas deferens that loops ventral to the testis. Small adults (Plehniella sp.) collected from body cavity of Pimelodus grosskopfii (Steindachner) from Cienega de Jobo and Canal del Dique (Colombia) differ from congeners by having a posteriorly-constricted body region, an anterior sucker with concentric rows of minute spines, an elongate anterior oesophageal swelling, short and wide caeca, and a male genital pore that opens proportionally more anteriad. This study nearly doubles the number of aporocotylids documented from South America Rivers and comprises the first record of a fish blood fluke from P. blochii, P. albofasciatus and P. grosskopfii as well as from Bolivia, Colombia, Guyana or Peru. PMID:26373332

  2. Monogeneans from Pangasiidae (Siluriformes) in Southeast Asia: IX. Two new species of Thaparocleidus Jain, 1952 (Ancylodiscoididae) from Pangasius mahakamensis.

    PubMed

    Pariselle, A; Lim, L H S; Lambert, A

    2005-12-01

    The examination of gill parasites from P. mahakamensis Pouyaud, Gustiano & Teugels, 2002 (Siluriformes, Pangasiidae) in Southeast Asia revealed the presence of three species of Monogenea. One (Thaparocleidus caecus (Mizelle & Kritsky, 1969)) had been previously described. The other two, belonging to Thaparocleidus Jain, 1952 (Monogenea, Ancylodiscoididae) as defined by Lim (1996) and Lim et al. (2001), are considered new species: T. pouyaudi n. sp. and T. teugelsi n. sp. PMID:16402564

  3. Neotropical Siluriformes as a Model for Insights on Determining Biodiversity of Animal Groups

    PubMed Central

    Ota, Renata Rúbia; Message, Hugo José; da Graça, Weferson Júnio; Pavanelli, Carla Simone

    2015-01-01

    We performed an analysis of the descriptions of new species of Neotropical Siluriformes (catfishes) to estimate the number of new species that remain to be described for a complete knowledge on biodiversity of this order, to verify the effectiveness of taxonomic support, and to identify trends and present relevant information for future policies. We conducted a literature review of species descriptions between January 1990 and August 2014. The following metadata were recorded from each article: year of publication, number of species, journal and impact factor, family(s) of the described species, number of authors, age of the authors and coauthors, country of the first author’s institution and ecoregion of the type-locality. From accumulation of descriptions, we built an estimate model for number of species remaining to be described. We found 595 described species in 402 articles. The data demonstrated that there has been an increased understanding of the diversity of Siluriformes over the last 25 years in the Neotropical region, although 35% of the species still remain to be described. The model estimated that with the current trends and incentives, the biodiversity will be known in almost seven decades. We have reinforced the idea that greater joint efforts should be made by society and the scientific community to obtain this knowledge in a shorter period of time through enhanced programs for promoting science, training and the advancement of professionals before undiscovered species become extinct. The model built in this study can be used for similar estimates of other groups of animals. PMID:26168270

  4. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    PubMed

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  5. Progenitors of type Ia supernovae

    NASA Astrophysics Data System (ADS)

    Maeda, Keiichi; Terada, Yukikatsu

    2016-07-01

    Natures of progenitors of type Ia Supernovae (SNe Ia) have not yet been clarified. There has been long and intensive discussion on whether the so-called single degenerate (SD) scenario or the double degenerate (DD) scenario, or anything else, could explain a major population of SNe Ia, but the conclusion has not yet been reached. With rapidly increasing observational data and new theoretical ideas, the field of studying the SN Ia progenitors has been quickly developing, and various new insights have been obtained in recent years. This paper aims at providing a summary of the current situation regarding the SN Ia progenitors, both in theory and observations. It seems difficult to explain the emerging diversity seen in observations of SNe Ia by a single population, and we emphasize that it is important to clarify links between different progenitor scenarios and different sub-classes of SNe Ia.

  6. A preliminary inventory of the catfishes of the lower Rio Nhamundá, Brazil (Ostariophysi, Siluriformes)

    PubMed Central

    Duarte Ribeiro, Emanuell; Nogueira Machado, Valéria; Hrbek, Tomas; Farias, Izeni Pires

    2015-01-01

    Abstract The Rio Nhamundá is a poorly-known clearwater river draining the southern Guiana Shield of Brazil. In this study we report the findings of a preliminary ichthyological survey, focusing on catfishes (Siluriformes). We identify a total of 36 species (31 genera, seven families) from the Nhamundá, including 11 species already recorded from the river. Overall, our survey results show that even rapid surveys can provide important information on Amazon fish biodiversity, suggesting potential new species, providing range extensions for nominal species, and additionally highlighting taxa in need of taxonomic revision and genetic study. As well as the traditional forms of data collected on biodiversity surveys (i.e. preserved specimen vouchers), our study also provides "new" types of data in the form of DNA barcodes and images of fishes exhibiting colouration in life, information that will be invaluable in future work addressing difficult groups. O Rio Nhamundá é um rio de água clara, pouco conhecido, que drena parte do Escudo das Guianas em território brasileiro. Nesse estudo, nós reportamos os resultados de um levantamento ictiofaunístico preliminar dessa área, tendo como foco os bagres (Siluriformes). Nós identificamos um total de 36 espécies (31 gêneros, sete famílias) provenientes de nossa coleta, e adicionamos 11 espécies já conhecidas para o rio. De maneira geral, os resultados de nossa pesquisa mostram que mesmo levantamentos rápidos podem gerar informações importantes sobre a biodiversidade de peixes amazônicos, sugerindo potenciais espécies novas, ampliando a área de distribuição de espécies, além de apontar a necessidade de revisões taxonômicas e estudos genéticos para alguns taxa. Para além das formas tradicionais de dados coletados em pesquisas de biodiversidade (i.e. espécimes preservados), nosso estudo fornece "novas" formas de dados, como DNA barcodes e imagens com o padrão de coloração dos espécimes vivos, informa

  7. A preliminary inventory of the catfishes of the lower Rio Nhamundá, Brazil (Ostariophysi, Siluriformes).

    PubMed

    Collins, Rupert A; Duarte Ribeiro, Emanuell; Nogueira Machado, Valéria; Hrbek, Tomas; Farias, Izeni Pires

    2015-01-01

    The Rio Nhamundá is a poorly-known clearwater river draining the southern Guiana Shield of Brazil. In this study we report the findings of a preliminary ichthyological survey, focusing on catfishes (Siluriformes). We identify a total of 36 species (31 genera, seven families) from the Nhamundá, including 11 species already recorded from the river. Overall, our survey results show that even rapid surveys can provide important information on Amazon fish biodiversity, suggesting potential new species, providing range extensions for nominal species, and additionally highlighting taxa in need of taxonomic revision and genetic study. As well as the traditional forms of data collected on biodiversity surveys (i.e. preserved specimen vouchers), our study also provides "new" types of data in the form of DNA barcodes and images of fishes exhibiting colouration in life, information that will be invaluable in future work addressing difficult groups. O Rio Nhamundá é um rio de água clara, pouco conhecido, que drena parte do Escudo das Guianas em território brasileiro. Nesse estudo, nós reportamos os resultados de um levantamento ictiofaunístico preliminar dessa área, tendo como foco os bagres (Siluriformes). Nós identificamos um total de 36 espécies (31 gêneros, sete famílias) provenientes de nossa coleta, e adicionamos 11 espécies já conhecidas para o rio. De maneira geral, os resultados de nossa pesquisa mostram que mesmo levantamentos rápidos podem gerar informações importantes sobre a biodiversidade de peixes amazônicos, sugerindo potenciais espécies novas, ampliando a área de distribuição de espécies, além de apontar a necessidade de revisões taxonômicas e estudos genéticos para alguns taxa. Para além das formas tradicionais de dados coletados em pesquisas de biodiversidade (i.e. espécimes preservados), nosso estudo fornece "novas" formas de dados, como DNA barcodes e imagens com o padrão de coloração dos espécimes vivos, informa

  8. Embryonic Heart Progenitors and Cardiogenesis

    PubMed Central

    Brade, Thomas; Pane, Luna S.; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl-Ludwig

    2013-01-01

    The mammalian heart is a highly specialized organ, comprised of many different cell types arising from distinct embryonic progenitor populations during cardiogenesis. Three precursor populations have been identified to contribute to different myocytic and nonmyocytic cell lineages of the heart: cardiogenic mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells (CNCCs). This review will focus on molecular cues necessary for proper induction, expansion, and lineage-specific differentiation of these progenitor populations during cardiac development in vivo. Moreover, we will briefly discuss how the knowledge gained on embryonic heart progenitor biology can be used to develop novel therapeutic strategies for the management of congenital heart disease as well as for improvement of cardiac function in ischemic heart disease. PMID:24086063

  9. The Progenitors of Thermonuclear Supernovae

    SciTech Connect

    Piersanti, L.; Straniero, O.; Tornambe, A.; Dominguez, I.

    2009-05-03

    In the framework of the rotating Double Degenerate Scenario for type Ia Supernovae progenitors, we show that the dichotomy between explosive events in early and late type galaxies can be easily explained. Assuming that more massive progenitors produce slow-decline (high-luminosity) light curve, it comes out that, at the current age of the Universe, in late type galaxies the continuous star formation provides very massive exploding objects (prompt component) corresponding to slow-decline (bright) SNe; on the other hand, in early type galaxies, where star formation ended many billions years ago, only low mass ''normal luminosity'' objects (delayed component) are present.

  10. Spine anatomy reveals the diversity of catfish through time: a case study of Synodontis (Siluriformes)

    NASA Astrophysics Data System (ADS)

    Pinton, Aurélie; Fara, Emmanuel; Otero, Olga

    2006-01-01

    Synodontis (Mochokidae, Siluriformes) is a freshwater catfish endemic to Africa. The 118 extant species are present in almost all hydrographic basins. Some species are restricted to a single stream, whereas others have a vast distribution. Synodontis is known in the fossil record since the Miocene, and its history depends on the connections among African basins through time. The identification of species in the fossil record is essential to reconstruct this historical pattern. Catfish pectoral and dorsal spines are robust, they preserve well and they form most of the fossil remains for the genus Synodontis. Unfortunately, the criteria for the identification of extant Synodontis species are not applicable to fossil specimens. Here, we define 11 original morphological characters that permit to discriminate four extant species from the Chad-Chari hydrographic system. Six of these characters are defined on pectoral spines and five on dorsal spines. We then show that these characters can be used successfully for identifying fossil specimens. In particular, we present a case study in which we identify Synodontis cf. schall and Brachysynodontis cf. batensoda in the hominid-bearing sector Toros-Menalla (Late Miocene, northern Chad). We show that spine anatomy can be a powerful tool to recognise catfish species through time and thus to identify historical diversity pattern.

  11. Molecular phylogeny and biogeography of air sac catfishes of the Heteropneustes fossilis species complex (Siluriformes: Heteropneustidae).

    PubMed

    Ratmuangkhwang, Sahat; Musikasinthorn, Prachya; Kumazawa, Yoshinori

    2014-10-01

    The air sac catfish, Heteropneustes fossilis (Siluriformes: Heteropneustidae), is widely distributed in freshwaters of the Indian subcontinent and mainland southeast Asia. No comprehensive molecular studies that cover the broad distributional areas have been carried out to date. Here, we conducted molecular phylogenetic analyses using both mitochondrial and nuclear gene sequences to suggest that the Heteropneustes fossilis species complex consists of three clades that may potentially be separate species with distinct geographical distribution (southeast Asia, northeastern India, and southwestern India). The first and second clades are more closely related to each other than they are to the third clade. Within the first clade there is a basal divergence of a subclade consisting of individuals from the Upper Irrawaddy River basin of Myanmar, which share some morphological traits with members of the Indian clades. Our molecular and morphological data are congruent with hypotheses that the Early-Middle Miocene disconnection between the paleo-Tsangpo River and the Irrawaddy River caused the vicariant divergence between southeast Asian and northeastern Indian clades, and that the southeast Asian Heteropneustes originated from the Upper Irrawaddy. PMID:24875251

  12. Cestodes (Caryophyllidea) of the stinging catfish Heteropneustes fossilis (Siluriformes: Heteropneustidae) from Asia.

    PubMed

    Ash, Anirban; Scholz, Tomáš; Oros, Mikuláš; Levron, Céline; Kar, Pradip Kumar

    2011-10-01

    The stinging catfish Heteropneustes fossilis (Bloch) (Siluriformes: Heteropneustidae) has been reported to harbor as many as 19 species of caryophyllidean tapeworms (Cestoda) of 11 genera in tropical Asia (Indomalayan zoogeographical region). However, a critical review of the species composition has shown that only 1 species, Lucknowia fossilisi Gupta, 1961 (Lytocestidae), is a specific parasite of H. fossilis. Three other species, Djombangia penetrans Bovien, 1926 (syn., Djombangia caballeroi Sahay and Sahay, 1977 ), Pseudocaryophyllaeus ritai Gupta and Singh, 1983 (syn. Pseudocaryophyllaeus lucknowensis Gupta and Sinha, 1984 ), and Pseudocaryophyllaeus tenuicollis (Bovien, 1926) Ash, Scholz, Oros and Kar, 2011 (syn. P. mackiewiczi Gupta and Parmar, 1982 ), were found only once. Lucknowia fossilisi is redescribed on the basis of new material collected in West Bengal and voucher specimens from Maharashtra, India. A total of 9 species of Capingentoides, Lucknowia, Lytocestus, Pseudoadenoscolex, Pseudocaryophyllaeus, Pseudoheteroinverta, and Sukhapatae are newly synonymized with L. fossilisi and previous synonymies of 9 other species, proposed by Hafeezulah (1993), are confirmed. Generic diagnosis of Lucknowia Gupta, 1961 is amended. In addition, 1 species of Pseudobatrachus and 2 species of the monotypic genera Pseudoneckinverta and Sudhaena are invalidated as nomina nuda. PMID:21561334

  13. Cytogenetic study of heptapterids (Teleostei, Siluriformes) with particular respect to the Nemuroglanis subclade.

    PubMed

    Kantek, Daniel Luis Zanella; Moreira Peres, Wellington Adriano; Moreira-Filho, Orlando

    2015-01-01

    The catfish family Heptapteridae (order Siluriformes) is endemic to the Neotropics and is one of the most common of the fish families in small bodies of water. Although over 200 species have been identified in this family, very few have been characterized cytogenetically. Here, we analyze the chromosome genomes of four species of Heptapteridae: Cetopsorhamdiaiheringi (Schubart & Gomes, 1959), 2n = 58, comprising 28 metacentric (m) + 26 submetacentric (sm) + 4 subtelomeric (st) chromosomes; Pimelodellavittata (Lütken, 1874), 2n = 46, comprising 16m + 22sm + 8st; Rhamdiapropequelen (Quoy & Gaimard, 1824), 2n = 58 comprising 26m + 16sm + 14st + 2 acrocentric; and Rhamdiopsispropemicrocephala (Lütken, 1874), 2n = 56, comprising 12m + 30sm + 14st. The nucleolus organizer regions (NORs) were located in a single chromosome pair in all species. The two species that belonged to the subclade Nemuroglanis, Cetopsorhamdiaiheringi and Rhamdiapropequelen, had a diploid chromosome number of 58 and an interstitial NOR adjacent to a C(+) block located on one of the larger chromosome pairs in the complement. Our results from conventional cytogenetic techniques in combination with FISH using 18S and 5S rDNA probes corroborated the taxonomical hypothesis for the formation of the Nemuroglanis subclade. PMID:25893072

  14. Cytogenetic study of heptapterids (Teleostei, Siluriformes) with particular respect to the Nemuroglanis subclade

    PubMed Central

    Kantek, Daniel Luis Zanella; Moreira Peres, Wellington Adriano; Moreira-Filho, Orlando

    2015-01-01

    Abstract The catfish family Heptapteridae (order Siluriformes) is endemic to the Neotropics and is one of the most common of the fish families in small bodies of water. Although over 200 species have been identified in this family, very few have been characterized cytogenetically. Here, we analyze the chromosome genomes of four species of Heptapteridae: Cetopsorhamdia iheringi (Schubart & Gomes, 1959), 2n = 58, comprising 28 metacentric (m) + 26 submetacentric (sm) + 4 subtelomeric (st) chromosomes; Pimelodella vittata (Lütken, 1874), 2n = 46, comprising 16m + 22sm + 8st; Rhamdia prope quelen (Quoy & Gaimard, 1824), 2n = 58 comprising 26m + 16sm + 14st + 2 acrocentric; and Rhamdiopsis prope microcephala (Lütken, 1874), 2n = 56, comprising 12m + 30sm + 14st. The nucleolus organizer regions (NORs) were located in a single chromosome pair in all species. The two species that belonged to the subclade Nemuroglanis, Cetopsorhamdia iheringi and Rhamdia prope quelen, had a diploid chromosome number of 58 and an interstitial NOR adjacent to a C+ block located on one of the larger chromosome pairs in the complement. Our results from conventional cytogenetic techniques in combination with FISH using 18S and 5S rDNA probes corroborated the taxonomical hypothesis for the formation of the Nemuroglanis subclade. PMID:25893072

  15. Progenitor Cells and Podocyte Regeneration

    PubMed Central

    Shankland, Stuart J.; Pippin, Jeffrey W.; Duffield, Jeremy S.

    2014-01-01

    The very limited ability of adult podocytes to proliferate in vivo is clinically significant because: podocytes form a vascular barrier which is functionally critical to the nephron; podocyte hypoplasia is a characteristic of disease; and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density is almost certainly reliant on regeneration by podocyte progenitors. However such putative progenitors have remained elusive until recently. In this review we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing ‘progenitor’ markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo with evidence from animal models suggesting a more limited role of PEC-capacity to serve as podocyte progenitors in adults. We will highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles including those which produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis. PMID:25217270

  16. Morphology and phylogeny of Thelohanellus marginatus n. sp. (Myxozoa: Myxosporea), a parasite infecting the gills of the fish Hypophthalmus marginatus (Teleostei: Pimelodidae) in the Amazon River.

    PubMed

    Rocha, Sónia; Casal, Graça; Velasco, Michele; Alves, Angela; Matos, Edilson; Al-Quraishy, Saleh; Azevedo, Carlos

    2014-01-01

    Thelohanellus marginatus n. sp., a new myxosporean parasite infecting the primary gill filaments of the teleost fish Hypophthalmus marginatus (Pimelodidae) in the Amazon River, is described on the basis of microscopic and molecular procedures. The parasite forms whitish and ellipsoidal cysts up to 250 μm in diam. Myxospores ellipsoidal with a slightly more pointed anterior end, measuring 17.1 ± 0.6 μm in length, 6.9 ± 0.4 μm in width, and 5.1 ± 0.5 μm in thickness. A single pyriform polar capsule, 9.0 ± 0.3 μm long and 6.1 ± 0.4 μm wide, positioned slightly right to the medial plane in valvular view, contains a polar filament arranged in 4-5 coils. Molecular analysis of the SSU rRNA gene by Maximum Parsimony, Neighbor-Joining, and Maximum Likelihood revealed the parasite clustering among other myxobolids, namely Henneguya and Myxobolus. Host affinity is supported as an important evolutionary signal for the phylogeny of myxobolids. The parasite here described represents the first record of the genus Thelohanellus Kudo, 1933 from the South American fauna. PMID:25039988

  17. New species and geographical records of dactylogyrids (Monogenea) of catfish (Siluriformes) from the Peruvian Amazonia.

    PubMed

    Mendoza-Palmero, Carlos A; Scholz, Tomáš; Mendoza-Franco, Edgar F; Kuchta, Roman

    2012-06-01

    Three new species of gill monogeneans (Dactylogyridae: Ancyrocephalinae) are described from siluriform catfish from Iquitos, Peru: Demidospermus mortenthaleri n. sp. from Brachyplatystoma juruense (Boulenger), Demidospermus brevicirrus n. sp. from Pimelodus sp., and Aphanoblastella aurorae n. sp. from Goeldiella eques (Müller & Troschel). Demidospermus mortenthaleri is characterized by a male copulatory organ (MCO) with a small loop at its middle portion; 2 types of hooks, of which pairs 5 and 6 are longer than the remaining hooks; a proximal subunit round and highly depressed thumb; and a sclerotized vagina with a round pad at the vaginal aperture. Demidospermus brevicirrus is distinguished from other congeners by the presence of a short, straight, and robust MCO and boot-shaped accessory piece with a hooked projection directed posteriorly. Aphanoblastella aurorae is the only species of the genus that possesses an arrow-shaped sclerotized vagina and a medial process on the dorsal bar. Another 6 dactylogyrids described previously are recorded for the first time from the Peruvian Amazonia: Cosmetocleithrum bulbocirrus Kritsky, Thatcher and Boeger, 1986 ; Vancleaveus fungulus Kritsky, Thatcher and Boeger, 1986 ; V. janauacaensis Kritsky, Thatcher and Boeger, 1986 ; V. platyrhynchi Kritsky, Thatcher and Boeger, 1986 ; Unilatus unilatus Mizelle and Kritsky, 1967 ; and U. brittani Mizelle, Kritsky and Crane, 1968 . Based on observations of specimens collected in the Peruvian Amazonia, new morphological data for these species are provided. Comparison of new specimens of U. unilatus and U. brittani with those of Unilatus brevispinus Suriano, 1985 and Unilatus longispinus Suriano, 1985 , both originally described from Brazil, has shown that they are conspecific. Therefore, the latter species were synonymized with U. unilatus and U. brittani , respectively. In addition, 56 undescribed monogeneans found in catfish from the Peruvian Amazonia, some of them probably belonging

  18. Evidence of Niche Partitioning under Ontogenetic Influences among Three Morphologically Similar Siluriformes in Small Subtropical Streams

    PubMed Central

    Bonato, Karine Orlandi; Fialho, Clarice Bernhardt

    2014-01-01

    Ontogenetic influences in patterns of niche breadth and feeding overlap were investigated in three species of Siluriformes (Heptapterus sp., Rhamdia quelen and Trichomycterus poikilos) aiming at understanding the species coexistence. Samplings were conducted bimonthly by electrofishing technique from June/2012 to June/2013 in ten streams of the northwestern state of Rio Grande do Sul, Brazil. The stomach contents of 1,948 individuals were analyzed by volumetric method, with 59 food items identified. In general Heptapterus sp. consumed a high proportion of Aegla sp., terrestrial plant remains and Megaloptera; R. quelen consumed fish, and Oligochaeta, followed by Aegla sp.; while the diet of T. poikilos was based on Simuliidae, Ephemeroptera and Trichoptera. Specie segregation was observed in the NMDS. Through PERMANOVA analysis feeding differences among species, and between a combination of species plus size classes were observed. IndVal showed which items were indicators of these differences. Niche breadth values were high for all species. The niche breadth values were low only for the larger size of R. quelen and Heptapterus sp. while T. poikilos values were more similar. Overall the species were a low feeding overlap values. The higher frequency of high feeding overlap was observed for interaction between Heptapterus sp. and T. poikilos. The null model confirmed the niche partitioning between the species. The higher frequency of high and intermediate feeding overlap values were reported to smaller size classes. The null model showed resource sharing between the species/size class. Therefore, overall species showed a resource partitioning because of the use of occasional items. However, these species share resources mainly in the early ontogenetic stages until the emphasized change of morphological characteristics leading to trophic niche expansion and the apparent segregation observed. PMID:25340614

  19. Evidence of niche partitioning under ontogenetic influences among three morphologically similar siluriformes in small subtropical streams.

    PubMed

    Bonato, Karine Orlandi; Fialho, Clarice Bernhardt

    2014-01-01

    Ontogenetic influences in patterns of niche breadth and feeding overlap were investigated in three species of Siluriformes (Heptapterus sp., Rhamdia quelen and Trichomycterus poikilos) aiming at understanding the species coexistence. Samplings were conducted bimonthly by electrofishing technique from June/2012 to June/2013 in ten streams of the northwestern state of Rio Grande do Sul, Brazil. The stomach contents of 1,948 individuals were analyzed by volumetric method, with 59 food items identified. In general Heptapterus sp. consumed a high proportion of Aegla sp., terrestrial plant remains and Megaloptera; R. quelen consumed fish, and Oligochaeta, followed by Aegla sp.; while the diet of T. poikilos was based on Simuliidae, Ephemeroptera and Trichoptera. Specie segregation was observed in the NMDS. Through PERMANOVA analysis feeding differences among species, and between a combination of species plus size classes were observed. IndVal showed which items were indicators of these differences. Niche breadth values were high for all species. The niche breadth values were low only for the larger size of R. quelen and Heptapterus sp. while T. poikilos values were more similar. Overall the species were a low feeding overlap values. The higher frequency of high feeding overlap was observed for interaction between Heptapterus sp. and T. poikilos. The null model confirmed the niche partitioning between the species. The higher frequency of high and intermediate feeding overlap values were reported to smaller size classes. The null model showed resource sharing between the species/size class. Therefore, overall species showed a resource partitioning because of the use of occasional items. However, these species share resources mainly in the early ontogenetic stages until the emphasized change of morphological characteristics leading to trophic niche expansion and the apparent segregation observed. PMID:25340614

  20. PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

    SciTech Connect

    Moriya, Takashi J.

    2012-05-01

    Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

  1. Odontode morphology and skin surface features of Andean astroblepid catfishes (Siluriformes, Astroblepidae).

    PubMed

    Schaefer, Scott A; Buitrago-Suárez, Uriel Angel

    2002-11-01

    specialized epithelial pit organs are unique to astroblepids among siluriforms and may be potentially important adaptations to life in torrential mountain streams. PMID:12353298

  2. The progenitors of stripped-envelope supernovae

    NASA Astrophysics Data System (ADS)

    Elias-Rosa, N.

    2013-05-01

    The type Ib/c SNe are those explosions which come from massive star populations, but lack hydrogen and helium. These have been proposed to originate in the explosions of massive Wolf-Rayet stars, and we should easily be able to detect the very luminous, young progenitors if they exist. However, there has not been any detection of progenitors so far. I present the study of two extinguished Type Ic SNe 2003jg and 2004cc. In both cases there is no clear evidence of a direct detection of their progenitors in deep pre-explosion images. Upper limits derived by inserting artificial stars of known brightness at random positions around the progenitor positions (M_v>-8.8 and M_v>-9 magnitudes for the progenitors of SN 2003jg and SN 2004cc, respectively) are brighter than those expected for a massive WC (Wolf-Rayet, carbon-rich) or WO (Wolf-Rayet, oxygen-rich) (e.g., approximately between -3 and -6 in the LMC). Therefore, this is perhaps further evidence that the most massive stars may give rise to black-holes forming SNe, or it is an undetected, compact massive star hidden by a thick dust lane. However the extinction toward these SNe is currently one of the largest known. Even if these results do not directly reveal the nature of the type Ic SN progenitors, they can help to characterize the dusty environment which surrounded the progenitor of the stripped-envelope CC-SNe.

  3. Progenitor genealogy in the developing cerebral cortex.

    PubMed

    Laguesse, Sophie; Peyre, Elise; Nguyen, Laurent

    2015-01-01

    The mammalian cerebral cortex is characterized by a complex histological organization that reflects the spatio-temporal stratifications of related stem and neural progenitor cells, which are responsible for the generation of distinct glial and neuronal subtypes during development. Some work has been done to shed light on the existing filiations between these progenitors as well as their respective contribution to cortical neurogenesis. The aim of the present review is to summarize the current views of progenitor hierarchy and relationship in the developing cortex and to further discuss future research directions that would help us to understand the molecular and cellular regulating mechanisms involved in cerebral corticogenesis. PMID:25141969

  4. Progenitor's Signatures in Type Ia Supernova Remnants

    NASA Astrophysics Data System (ADS)

    Chiotellis, A.; Kosenko, D.; Schure, K. M.; Vink, J.

    2013-01-01

    The remnants of Type Ia supernovae (SNe Ia) can provide important clues about their progenitor histories. We discuss two well-observed supernova remnants (SNRs) that are believed to have resulted from SNe Ia, and use various tools to shed light on the possible progenitor histories. We find that Kepler's SNR is consistent with a symbiotic binary progenitor consisting of a white dwarf and an AGB star. Our hydrosimulations can reproduce the observed kinematic and morphological properties. For Tycho's remnant we use the characteristics of the X-ray spectrum and kinematics to show that the ejecta has likely interacted with dense circumstellar gas.

  5. Endothelial progenitor cells: identity defined?

    PubMed Central

    Timmermans, Frank; Plum, Jean; Yöder, Mervin C; Ingram, David A; Vandekerckhove, Bart; Case, Jamie

    2009-01-01

    Abstract In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133+ cells or CD45+ haematopoietic cells. PMID:19067770

  6. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs

    PubMed Central

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-01-01

    Summary In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. PMID:26972603

  7. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

    PubMed

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-03-21

    In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. PMID:26972603

  8. STELLAR BINARY COMPANIONS TO SUPERNOVA PROGENITORS

    SciTech Connect

    Kochanek, Christopher S.

    2009-12-20

    For typical models of binary statistics, 50%-80% of core-collapse supernova (ccSN) progenitors are members of a stellar binary at the time of the explosion. Independent of any consequences of mass transfer, this has observational consequences that can be used to study the binary properties of massive stars. In particular, the secondary companion to the progenitor of a Type Ib/c SN is frequently (approx50%) the more optically luminous star since the high effective temperatures of the stripped progenitors make it relatively easy for a lower luminosity, cooler secondary to emit more optical light. Secondaries to the lower mass progenitors of Type II SN will frequently produce excess blue emission relative to the spectral energy distribution of the red primary. Available data constrain the models weakly. Any detected secondaries also provide an independent lower bound on the progenitor mass and, for historical SN, show that it was not a Type Ia event. Bright ccSN secondaries have an unambiguous, post-explosion observational signature-strong, blueshifted, relatively broad absorption lines created by the developing SN remnant (SNR). These can be used to locate historical SN with bright secondaries, confirm that a source is a secondary, and, potentially, measure abundances of ccSN ejecta. Luminous, hot secondaries will re-ionize the SNR on timescales of 100-1000 yr that are faster than re-ionization by the reverse shock, creating peculiar H II regions due to the high metallicity and velocities of the ejecta.

  9. Exploring the Progenitors of Fast Radio Bursts

    NASA Astrophysics Data System (ADS)

    Burke-Spolaor, Sarah; Kramer, Michael; Bhat, Ramesh; Kulkarni, S. R.; Keller, Stefan; Champion, David; Flynn, Chris; Kasliwal, Mansi

    2014-10-01

    Fast Radio Bursts (FRBs) are millisecond bursts that are broadly evidenced to arise from extragalactic, but yet unknown, progenitors. They have presented a true mystery in that so far no progenitor theory can adequately account for their observed properties. We request observations that will glean basic information on FRB progenitors. Our observations will execute a specific test of whether FRBs originate in nearby galaxies. We have also designed our target field and time request to enable a thorough exploration of optical counterparts before, during, and after any detected FRB episode. Additionally, with a number depending on the typical distance to FRBs, our observations will raise the running list of total FRB discoveries by 10-60%.

  10. Progenitor cells in the adult pancreas.

    PubMed

    Holland, Andrew M; Góñez, L Jorge; Harrison, Leonard C

    2004-01-01

    The beta-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or beta-cell progenitors and the molecular mechanisms underlying beta-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, beta-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of beta-cells. PMID:14737742

  11. Derivation of high-purity oligodendroglial progenitors.

    PubMed

    Hatch, Maya N; Nistor, Gabriel; Keirstead, Hans S

    2009-01-01

    Oligodendrocytes are a type of glial cells that play a critical role in supporting the central nervous system (CNS), in particular insulating axons within the CNS by wrapping them with a myelin sheath, thereby enabling saltatory conduction. They are lost, and myelin damaged - demyelination - in a wide variety of neurological disorders. Replacing depleted cell types within demyelinated areas, however, has been shown experimentally to achieve remyelination and so help restore function. One method to produce oligodendrocytes for cellular replacement therapies is through the use of progenitor or stem cells. The ability to differentiate progenitor or stem cells into high-purity fates not only permits the generation of specific cells for transplantation therapies, but also provides powerful tools for studying cellular mechanisms of development. This chapter outlines methods of generating high-purity OPCs from multipotent neonatal progenitor or human embryonic stem cells. PMID:19378196

  12. Pigment Cell Progenitors in Zebrafish Remain Multipotent through Metamorphosis.

    PubMed

    Singh, Ajeet Pratap; Dinwiddie, April; Mahalwar, Prateek; Schach, Ursula; Linker, Claudia; Irion, Uwe; Nüsslein-Volhard, Christiane

    2016-08-01

    The neural crest is a transient, multipotent embryonic cell population in vertebrates giving rise to diverse cell types in adults via intermediate progenitors. The in vivo cell-fate potential and lineage segregation of these postembryonic progenitors is poorly understood, and it is unknown if and when the progenitors become fate restricted. We investigate the fate restriction in the neural crest-derived stem cells and intermediate progenitors in zebrafish, which give rise to three distinct adult pigment cell types: melanophores, iridophores, and xanthophores. By inducing clones in sox10-expressing cells, we trace and quantitatively compare the pigment cell progenitors at four stages, from embryogenesis to metamorphosis. At all stages, a large fraction of the progenitors are multipotent. These multipotent progenitors have a high proliferation ability, which diminishes with fate restriction. We suggest that multipotency of the nerve-associated progenitors lasting into metamorphosis may have facilitated the evolution of adult-specific traits in vertebrates. PMID:27453500

  13. The progenitors of subluminous type Ia supernovae

    SciTech Connect

    Howell, D. Andrew

    2001-02-01

    We find that spectroscopically peculiar subluminous SNe Ia come from an old population. Of the thirteen subluminous SNe Ia known, nine are found in E/S0 galaxies, and the remainder are found in early-type spirals. The probability that this is a chance occurrence is only 0.1%. The finding that subluminous SNe Ia are associated with an older stellar population indicates that for a sufficiently large lookback time (already accessible in current high redshift searches) they will not be found. Due to a scarcity in old populations, hydrogen and helium main sequence stars and He red giant stars that undergo Roche lobe overflow are unlikely to be the progenitors of subluminous SNe Ia. Earlier findings that overluminous SNe Ia (DELTA m{sub 15} (B) < 0.94) come from a young progenitor population are confirmed. The fact that subluminous SNe Ia and overluminous SNe Ia come from different progenitor populations and also have different properties is a prediction of the CO white dwarf merger progenitor scenario.

  14. Human Liver Progenitor Cells for Liver Repair

    PubMed Central

    Lombard, Catherine A.; Prigent, Julie; Sokal, Etienne M.

    2013-01-01

    Because of their high proliferative capacity, resistance to cryopreservation, and ability to differentiate into hepatocyte-like cells, stem and progenitor cells have recently emerged as attractive cell sources for liver cell therapy, a technique used as an alternative to orthotopic liver transplantation in the treatment of various hepatic ailments ranging from metabolic disorders to end-stage liver disease. Although stem and progenitor cells have been isolated from various tissues, obtaining them from the liver could be an advantage for the treatment of hepatic disorders. However, the techniques available to isolate these stem/progenitor cells are numerous and give rise to cell populations with different morphological and functional characteristics. In addition, there is currently no established consensus on the tests that need to be performed to ensure the quality and safety of these cells when used clinically. The purpose of this review is to describe the different types of liver stem/progenitor cells currently reported in the literature, discuss their suitability and limitations in terms of clinical applications, and examine how the culture and transplantation techniques can potentially be improved to achieve a better clinical outcome. PMID:26858860

  15. In vivo identification of periodontal progenitor cells.

    PubMed

    Roguljic, H; Matthews, B G; Yang, W; Cvija, H; Mina, M; Kalajzic, I

    2013-08-01

    The periodontal ligament contains progenitor cells; however, their identity and differentiation potential in vivo remain poorly characterized. Previous results have suggested that periodontal tissue progenitors reside in perivascular areas. Therefore, we utilized a lineage-tracing approach to identify and track periodontal progenitor cells from the perivascular region in vivo. We used an alpha-smooth muscle actin (αSMA) promoter-driven and tamoxifen-inducible Cre system (αSMACreERT2) that, in combination with a reporter mouse line (Ai9), permanently labels a cell population, termed 'SMA9'. To trace the differentiation of SMA9-labeled cells into osteoblasts/cementoblasts, we utilized a Col2.3GFP transgene, while expression of Scleraxis-GFP was used to follow differentiation into periodontal ligament fibroblasts during normal tissue formation and remodeling following injury. In uninjured three-week-old SMA9 mice, tamoxifen labeled a small population of cells in the periodontal ligament that expanded over time, particularly in the apical region of the root. By 17 days and 7 weeks after labeling, some SMA9-labeled cells expressed markers indicating differentiation into mature lineages, including cementocytes. Following injury, SMA9 cells expanded, and differentiated into cementoblasts, osteoblasts, and periodontal ligament fibroblasts. SMA9-labeled cells represent a source of progenitors that can give rise to mature osteoblasts, cementoblasts, and fibroblasts within the periodontium. PMID:23735585

  16. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    SciTech Connect

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R.; Murphy, Jeremiah W.; Dolphin, Andrew E. E-mail: adolphin@raytheon.com

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  17. Monogeneans from Pangasiidae (Siluriformes) in Southeast Asia: III. Five new species of Thaparocleidus Jain, 1952 (Ancylodiscoididae) from Pangasius bocourti, P. djambal and P. hypophthalmus.

    PubMed

    Pariselle, A; Lim, L H S; Lambert, A

    2002-09-01

    The examination of gill parasites from Pangasius bocourti Sauvage, 1880; P. djambal Bleeker, 1846; P. hypophthalmus (Sauvage, 1878) and P. gigas Chevey, 1930 (Siluriformes, Pangasiidae) revealed the presence of seven species of Monogenea among which five are considered new species. They all belong to Thaparocleidus Jain, 1952 (Ancylodiscoididae) as defined by Lim (1996) and Lim et al. (2001). P. bocourti: T. combesi n. sp., T. komarudini n. sp. and T. vietnamensis n. sp. P. djambal: T. caecus (Mizelle & Kritsky, 1969), T. combesi n. sp., T. euzeti n. sp., T. komarudini n. sp. and T. sadilii n. sp. P. hypophthalmus: T. caecus, T. siamensis (Lim, 1990) and T. vietnamensis n. sp. P. gigas: no Monogenea were found on this host species. PMID:12375363

  18. Interneuron Progenitor Transplantation to Treat CNS Dysfunction

    PubMed Central

    Chohan, Muhammad O.; Moore, Holly

    2016-01-01

    Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field. PMID:27582692

  19. Progenitor cells for ocular surface regenerative therapy.

    PubMed

    Casaroli-Marano, Ricardo P; Nieto-Nicolau, Nuria; Martínez-Conesa, Eva M

    2013-01-01

    The integrity and normal function of the corneal epithelium are essential for maintaining the cornea's transparency and vision. The existence of a cell population with progenitor characteristics in the limbus maintains a dynamic of constant epithelial repair and renewal. Currently, cell-based therapies for bio-replacement, such as cultured limbal epithelial transplantation and cultured oral mucosal epithelial transplantation, present very encouraging clinical results for treating limbal stem cell deficiencies. Another emerging therapeutic strategy consists of obtaining and implementing human progenitor cells of different origins using tissue engineering methods. The development of cell-based therapies using stem cells, such as human adult mesenchymal stromal cells, represents a significant breakthrough in the treatment of certain eye diseases and also offers a more rational, less invasive and more physiological approach to ocular surface regeneration. PMID:23257987

  20. Noninvasive Imaging of Administered Progenitor Cells

    SciTech Connect

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90

  1. Cardiac progenitor cells for heart repair

    PubMed Central

    Le, TYL; Chong, JJH

    2016-01-01

    Stem cell therapy is being investigated as an innovative and promising strategy to restore cardiac function in patients with heart failure. Several stem cell populations, including adult (multipotent) stem cells from developed organs and tissues, have been tested for cardiac repair with encouraging clinical and pre-clinical results. The heart has been traditionally considered a post-mitotic organ, however, this view has recently changed with the identification of stem/progenitor cells residing within the adult heart. Given their cardiac developmental origins, these endogenous cardiac progenitor cells (CPCs) may represent better candidates for cardiac cell therapy compared with stem cells from other organs such as the bone marrow and adipose tissue. This brief review will outline current research into CPC populations and their cardiac repair/regenerative potential. PMID:27551540

  2. POPULATION SYNTHESIS AND GAMMA RAY BURST PROGENITORS

    SciTech Connect

    C. L. FREYER

    2000-12-11

    Population synthesis studies of binaries are always limited by a myriad of uncertainties from the poorly understood effects of binary mass transfer and common envelope evolution to the many uncertainties that still remain in stellar evolution. But the importance of these uncertainties depends both upon the objects being studied and the questions asked about these objects. Here I review the most critical uncertainties in the population synthesis of gamma-ray burst progenitors. With a better understanding of these uncertainties, binary population synthesis can become a powerful tool in understanding, and constraining, gamma-ray burst models. In turn, as gamma-ray bursts become more important as cosmological probes, binary population synthesis of gamma-ray burst progenitors becomes an important tool in cosmology.

  3. Human progenitor cells for bone engineering applications.

    PubMed

    de Peppo, G M; Thomsen, P; Karlsson, C; Strehl, R; Lindahl, A; Hyllner, J

    2013-06-01

    In this report, the authors review the human skeleton and the increasing burden of bone deficiencies, the limitations encountered with the current treatments and the opportunities provided by the emerging field of cell-based bone engineering. Special emphasis is placed on different sources of human progenitor cells, as well as their pros and cons in relation to their utilization for the large-scale construction of functional bone-engineered substitutes for clinical applications. It is concluded that, human pluripotent stem cells represent a valuable source for the derivation of progenitor cells, which combine the advantages of both embryonic and adult stem cells, and indeed display high potential for the construction of functional substitutes for bone replacement therapies. PMID:23642054

  4. Chondrogenic Progenitor Cells Respond to Cartilage Injury

    PubMed Central

    Choe, Hyeonghun; Zheng, Hongjun; Yu, Yin; Jang, Keewoong; Walter, Morgan W.; Lehman, Abigail D.; Ding, Lei; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Objective Hypocellularity resulting from chondrocyte death in the aftermath of mechanical injury is thought to contribute to posttraumatic osteoarthritis. However, we observed that nonviable areas in cartilage injured by blunt impact were repopulated within 7–14 days by cells that appeared to migrate from the surrounding matrix. The aim of this study was to assess our hypothesis that the migrating cell population included chondrogenic progenitor cells that were drawn to injured cartilage by alarmins. Methods Osteochondral explants obtained from mature cattle were injured by blunt impact or scratching, resulting in localized chondrocyte death. Injured sites were serially imaged by confocal microscopy, and migrating cells were evaluated for chondrogenic progenitor characteristics. Chemotaxis assays were used to measure the responses to chemokines, injury-conditioned medium, dead cell debris, and high mobility group box chromosomal protein 1 (HMGB-1). Results Migrating cells were highly clonogenic and multipotent and expressed markers associated with chondrogenic progenitor cells. Compared with chondrocytes, these cells overexpressed genes involved in proliferation and migration and underexpressed cartilage matrix genes. They were more active than chondrocytes in chemotaxis assays and responded to cell lysates, conditioned medium, and HMGB-1. Glycyrrhizin, a chelator of HMGB-1 and a blocking antibody to receptor for advanced glycation end products (RAGE), inhibited responses to cell debris and conditioned medium and reduced the numbers of migrating cells on injured explants. Conclusion Injuries that caused chondrocyte death stimulated the emergence and homing of chondrogenic progenitor cells, in part via HMGB-1 release and RAGE-mediated chemotaxis. Their repopulation of the matrix could promote the repair of chondral damage that might otherwise contribute to progressive cartilage loss. PMID:22777600

  5. Multipotent Hematopoietic Progenitors Divide Asymmetrically to Create Progenitors of the Lymphomyeloid and Erythromyeloid Lineages

    PubMed Central

    Görgens, André; Ludwig, Anna-Kristin; Möllmann, Michael; Krawczyk, Adalbert; Dürig, Jan; Hanenberg, Helmut; Horn, Peter A.; Giebel, Bernd

    2014-01-01

    Summary Hematopoietic stem and progenitor cells (HSPCs) can self-renew and create committed progenitors, a process supposed to involve asymmetric cell divisions (ACDs). Previously, we had linked the kinetics of CD133 expression with ACDs but failed to detect asymmetric segregation of classical CD133 epitopes on fixed, mitotic HSPCs. Now, by using a novel anti-CD133 antibody (HC7), we confirmed the occurrence of asymmetric CD133 segregation on paraformaldehyde-fixed and living HSPCs. After showing that HC7 binding does not recognizably affect biological features of human HSPCs, we studied ACDs in different HSPC subtypes and determined the developmental potential of arising daughter cells at the single-cell level. Approximately 70% of the HSPCs of the multipotent progenitor (MPP) fraction studied performed ACDs, and about 25% generated lymphoid-primed multipotent progenitor (LMPP) as wells as erythromyeloid progenitor (EMP) daughter cells. Since MPPs hardly created daughter cells maintaining MPP characteristics, our data suggest that under conventional culture conditions, ACDs are lineage instructive rather than self-renewing. PMID:25448068

  6. New species of Demidospermus (Monogenea: Dactylogyridae) of pimelodid catfish (Siluriformes) from Peruvian Amazonia and the reassignment of Urocleidoides lebedevi Kritsky and Thatcher, 1976.

    PubMed

    Mendoza-Palmero, Carlos A; Scholz, Tomáš

    2011-08-01

    Three new species of Demidospermus Suriano, 1983 were found in mixed infections on the gills of 4 pimelodid catfish collected in the Amazon River basin around Iquitos, Peru, namely, Demidospermus peruvianus n. sp. from Pimelodus ornatus Kner, Pimelodus blochii Valenciennes, Pimelodus sp. (type host), and an unidentified pimelodid. Demidospermus peruvianus n. sp. (type host, Pimelodus sp.) is characterized by the presence of the male copulatory organ with 2 lateral, thickened projections, and the vagina with a loop at its middle. Demidospermus curvovaginatus n. sp. from P. ornatus , Pimelodus sp. (type host), and Pimelodidae gen. sp. differs from its congeners by the presence of a funnel-shaped vagina directed posteriorly and a male copulatory organ with a small lateral projection at its base. Demidospermus striatus n. sp. from P. blochii and Pimelodus sp. (type host) is distinguished by a cup-shaped vagina with conspicuous ridges at the perimeter of the aperture with a short tube directed anteriorly. In addition, Urocleidoides lebedevi Kritsky and Thatcher, 1976 , a parasite originally described from the gills of Pimelodus grosskopfii (type host) from Colombia, is transferred to Demidospermus , based on morphological characters that we observed in type specimens. PMID:21506840

  7. TOX3 regulates neural progenitor identity.

    PubMed

    Sahu, Sanjeeb Kumar; Fritz, Alina; Tiwari, Neha; Kovacs, Zsuzsa; Pouya, Alireza; Wüllner, Verena; Bora, Pablo; Schacht, Teresa; Baumgart, Jan; Peron, Sophie; Berninger, Benedikt; Tiwari, Vijay K; Methner, Axel

    2016-07-01

    The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromatin immunoprecipitation assays. In line with this, over-expression of Tox3 increased Nestin promoter activity, which was cooperatively enhanced by treatment with the stem cell self-renewal promoting Notch ligand Jagged and repressed by pharmacological inhibition of Notch signaling. Knockdown of Tox3 in the subventricular zone of E12.5 mouse embryos by in utero electroporation of Tox3 shRNA revealed a reduced Nestin expression and decreased proliferation at E14 and a reduced migration to the cortical plate in E16 embryos in electroporated cells. Together, these results argue for a role of Tox3 in the development of the nervous system. PMID:27080130

  8. Endothelial progenitor cells in hematologic malignancies

    PubMed Central

    Saulle, Ernestina; Castelli, Germana; Pelosi, Elvira

    2016-01-01

    Studies carried out in the last years have improved the understanding of the cellular and molecular mechanisms controlling angiogenesis during adult life in normal and pathological conditions. Some of these studies have led to the identification of some progenitor cells that sustain angiogenesis through indirect, paracrine mechanisms (hematopoietic angiogenic cells) and through direct mechanisms, i.e., through their capacity to generate a progeny of phenotypically and functionally competent endothelial cells [endothelial colony forming cells (ECFCs)]. The contribution of these progenitors to angiogenetic processes under physiological and pathological conditions is intensively investigated. Angiogenetic mechanisms are stimulated in various hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma, resulting in an increased angiogenesis that contributes to disease progression. In some of these conditions there is preliminary evidence that some endothelial cells could derive from the malignant clone, thus leading to the speculation that the leukemic cell derives from the malignant transformation of a hemangioblastic progenitor, i.e., of a cell capable of differentiation to the hematopoietic and to the endothelial cell lineages. Our understanding of the mechanisms underlying increased angiogenesis in these malignancies not only contributed to a better knowledge of the mechanisms responsible for tumor progression, but also offered the way for the discovery of new therapeutic targets. PMID:27583252

  9. EVOLUTION OF PROGENITORS FOR ELECTRON CAPTURE SUPERNOVAE

    SciTech Connect

    Takahashi, Koh; Umeda, Hideyuki; Yoshida, Takashi E-mail: umeda@astron.s.u-tokyo.ac.jp

    2013-07-01

    We provide progenitor models for electron capture supernovae (ECSNe) with detailed evolutionary calculation. We include minor electron capture nuclei using a large nuclear reaction network with updated reaction rates. For electron capture, the Coulomb correction of rates is treated and the contribution from neutron-rich isotopes is taken into account in each nuclear statistical equilibrium (NSE) composition. We calculate the evolution of the most massive super asymptotic giant branch stars and show that these stars undergo off-center carbon burning and form ONe cores at the center. These cores become heavier up to the critical mass of 1.367 M{sub Sun} and keep contracting even after the initiation of O+Ne deflagration. Inclusion of minor electron capture nuclei causes convective URCA cooling during the contraction phase, but the effect on the progenitor evolution is small. On the other hand, electron capture by neutron-rich isotopes in the NSE region has a more significant effect. We discuss the uniqueness of the critical core mass for ECSNe and the effect of wind mass loss on the plausibility of our models for ECSN progenitors.

  10. Endothelial progenitor cells in hematologic malignancies.

    PubMed

    Testa, Ugo; Saulle, Ernestina; Castelli, Germana; Pelosi, Elvira

    2016-01-01

    Studies carried out in the last years have improved the understanding of the cellular and molecular mechanisms controlling angiogenesis during adult life in normal and pathological conditions. Some of these studies have led to the identification of some progenitor cells that sustain angiogenesis through indirect, paracrine mechanisms (hematopoietic angiogenic cells) and through direct mechanisms, i.e., through their capacity to generate a progeny of phenotypically and functionally competent endothelial cells [endothelial colony forming cells (ECFCs)]. The contribution of these progenitors to angiogenetic processes under physiological and pathological conditions is intensively investigated. Angiogenetic mechanisms are stimulated in various hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma, resulting in an increased angiogenesis that contributes to disease progression. In some of these conditions there is preliminary evidence that some endothelial cells could derive from the malignant clone, thus leading to the speculation that the leukemic cell derives from the malignant transformation of a hemangioblastic progenitor, i.e., of a cell capable of differentiation to the hematopoietic and to the endothelial cell lineages. Our understanding of the mechanisms underlying increased angiogenesis in these malignancies not only contributed to a better knowledge of the mechanisms responsible for tumor progression, but also offered the way for the discovery of new therapeutic targets. PMID:27583252

  11. Defining human dendritic cell progenitors by multiparametric flow cytometry.

    PubMed

    Breton, Gaëlle; Lee, Jaeyop; Liu, Kang; Nussenzweig, Michel C

    2015-09-01

    Human dendritic cells (DCs) develop from progressively restricted bone marrow (BM) progenitors: these progenitor cells include granulocyte, monocyte and DC progenitor (GMDP) cells; monocyte and DC progenitor (MDP) cells; and common DC progenitor (CDP) and DC precursor (pre-DC) cells. These four DC progenitors can be defined on the basis of the expression of surface markers such as CD34 and hematopoietin receptors. In this protocol, we describe five multiparametric flow cytometry panels that can be used as a tool (i) to simultaneously detect or phenotype the four DC progenitors, (ii) to isolate DC progenitors to enable in vitro differentiation or (iii) to assess the in vitro differentiation and proliferation of DC progenitors. The entire procedure from isolation of cells to flow cytometry can be completed in 3-7 h. This protocol provides optimized antibody panels, as well as gating strategies, for immunostaining of BM and cord blood specimens to study human DC hematopoiesis in health, disease and vaccine settings. PMID:26292072

  12. Transformation of erythroid progenitors by viral and cellular tyrosine kinases.

    PubMed

    Beug, H; Schroeder, C; Wessely, O; Deiner, E; Meyer, S; Ischenko, I D; Hayman, M J

    1995-08-01

    Recently, two different normal avian erythroid progenitors were described. They differ in the receptor tyrosine kinases they express and in their ability to undergo self-renewal in culture. A common progenitor, termed stem cell factor (SCF) progenitor, expresses the receptor for avian SCF c-Kit, and undergoes short-term self-renewal when grown in the presence of avian SCF. A second progenitor, referred to as SCF/transforming growth factor-alpha progenitor, coexpresses c-Kit and the avian epidermal growth factor receptor homologue c-ErbB. These progenitors undergo sustained self-renewal when grown in the presence of transforming growth factor-alpha plus estradiol. The phenotype of the normal SCF/transforming growth factor-alpha progenitors closely corresponded to that of erythroid cells transformed by the tyrosine kinase oncogenes v-erbB or v-sea. This suggested that these cells, but not the SCF progenitors, would be the target cells for erythroblast transformation by these oncogenes. However, we demonstrate that both progenitor cells can be transformed by the v-erbB and v-sea oncogenes and also by the ligand-activated proto-oncogene product c-ErbB. We conclude that the target cell specificity of certain tyrosine kinase oncoproteins for erythroid cells is a reflection of their ability to provide signals for self-renewal that normally emanate from the endogenous c-ErbB protein. PMID:8547228

  13. Defining human dendritic cell progenitors by multiparametric flow cytometry

    PubMed Central

    Breton, Gaëlle; Lee, Jaeyop; Liu, Kang; Nussenzweig, Michel C

    2015-01-01

    Human dendritic cells (DCs) develop from progressively restricted bone marrow (BM) progenitors: these progenitor cells include granulocyte, monocyte and DC progenitor (GMDP) cells; monocyte and DC progenitor (MDP) cells; and common DC progenitor (CDP) and DC precursor (pre-DC) cells. These four DC progenitors can be defined on the basis of the expression of surface markers such as CD34 and hematopoietin receptors. In this protocol, we describe five multiparametric flow cytometry panels that can be used as a tool (i) to simultaneously detect or phenotype the four DC progenitors, (ii) to isolate DC progenitors to enable in vitro differentiation or (iii) to assess the in vitro differentiation and proliferation of DC progenitors. The entire procedure from isolation of cells to flow cytometry can be completed in 3–7 h. This protocol provides optimized antibody panels, as well as gating strategies, for immunostaining of BM and cord blood specimens to study human DC hematopoiesis in health, disease and vaccine settings. PMID:26292072

  14. Nutritional regulation of stem and progenitor cells in Drosophila

    PubMed Central

    Shim, Jiwon; Gururaja-Rao, Shubha; Banerjee, Utpal

    2013-01-01

    Stem cells and their progenitors are maintained within a microenvironment, termed the niche, through local cell-cell communication. Systemic signals originating outside the niche also affect stem cell and progenitor behavior. This review summarizes studies that pertain to nutritional effects on stem and progenitor cell maintenance and proliferation in Drosophila. Multiple tissue types are discussed that utilize the insulin-related signaling pathway to convey nutritional information either directly to these progenitors or via other cell types within the niche. The concept of systemic control of these cell types is not limited to Drosophila and may be functional in vertebrate systems, including mammals. PMID:24255094

  15. Cell culture: Progenitor cells from human brain after death

    NASA Astrophysics Data System (ADS)

    Palmer, Theo D.; Schwartz, Philip H.; Taupin, Philippe; Kaspar, Brian; Stein, Stuart A.; Gage, Fred H.

    2001-05-01

    Culturing neural progenitor cells from the adult rodent brain has become routine and is also possible from human fetal tissue, but expansion of these cells from postnatal and adult human tissue, although preferred for ethical reasons, has encountered problems. Here we describe the isolation and successful propagation of neural progenitor cells from human postmortem tissues and surgical specimens. Although the relative therapeutic merits of adult and fetal progenitor cells still need to be assessed, our results may extend the application of these progenitor cells in the treatment of neurodegenerative diseases.

  16. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  17. ALDH1B1 is a potential stem / progenitor marker for multiple pancreas progenitor pools

    PubMed Central

    Ioannou, Marilia; Serafimidis, Ioannis; Arnes, Luis; Sussel, Lori; Singh, Surendra; Vasiliou, Vasilis; Gavalas, Anthony

    2013-01-01

    Aldehyde Dehydrogenase (ALDH) genes are increasingly associated with stem / progenitor cell status but their role in the maintenance of pluripotency remains uncertain. In a screen conducted for downstream Ngn3 target genes using ES derived pancreas progenitors we identified Aldh1b1, encoding a mitochondrial enzyme, as one of the genes strongly up regulated in response to Ngn3 expression. We found both by in situ hybridization and immunofluorescence using a specific antibody that ALDH1B1 is exclusively expressed in the emerging pancreatic buds of the early embryo (9.5 dpc) in a Pdx1 dependent manner. Around the time of secondary transition, ALDH1B1 expression was restricted in the tip tripotent progenitors of the branching epithelium and in a subset of the trunk epithelium. Expression in the latter was Ngn3 dependent. Subsequently, ALDH1B1 expression persisted only in the tip cells that become restricted to the exocrine lineage and declined rapidly as these cells mature. In the adult pancreas we identified rare ALDH1B1+ cells that become abundant following pancreas injury in either the caerulein or streptozotocin paradigms. Blocking ALDH catalytic activity in pancreas embryonic explants resulted in reduced size of the explants and accelerated differentiation suggesting for the first time that ALDH activity may be necessary in the developing pancreas for the maintenance and expansion of progenitor pools. PMID:23142317

  18. Adipose Tissue Residing Progenitors (Adipocyte Lineage Progenitors and Adipose Derived Stem Cells (ADSC)

    PubMed Central

    Berry, Ryan; Rodeheffer, Matthew S.; Rosen, Clifford J.; Horowitz, Mark C.

    2015-01-01

    The formation of brown, white and beige adipocytes have been a subject of intense scientific interest in recent years due to the growing obesity epidemic in the United States and around the world. This interest has led to the identification and characterization of specific tissue resident progenitor cells that give rise to each adipocyte population in vivo. However, much still remains to be discovered about each progenitor population in terms of their “niche” within each tissue and how they are regulated at the cellular and molecular level during healthy and diseased states. While our knowledge of brown, white and beige adipose tissue is rapidly increasing, little is still known about marrow adipose tissue and its progenitor despite recent studies demonstrating possible roles for marrow adipose tissue in regulating the hematopoietic space and systemic metabolism at large. This chapter focuses on our current knowledge of brown, white, beige and marrow adipose tissue with a specific focus on the formation of each tissue from tissue resident progenitor cells. PMID:26526875

  19. Type Ia Supernova Progenitors, Cosmology, and Systematics

    NASA Astrophysics Data System (ADS)

    Hayden, Brian

    2013-01-01

    Type Ia supernovae have become fundamental tools for cosmology, but their progenitors, explosion mechanism, and dependence on environment remain key problems to be solved to improve their reliability as cosmological distance estimators. In this talk I will present my research into the nature of SN Ia explosions and their environments, and discuss ongoing efforts to understand systematic errors in SN Ia distance measurements. Using SDSS-II SNe, I developed the 2-stretch fitting method for SN Ia light curves. The 2-stretch method allows the rise and decline portions of the light curve to be fit separately, and as a result I discovered that SN Ia light curves with a normal decline rate show a large variation in rise times. This departure from the single stretch model also results in an average rise time of about 17.5 days, 2 days shorter than previously accepted results. While accurate measurements of the rise time do not significantly improve cosmological results, they do improve the estimate of 56-Ni yield, which is an important constraint in theoretical modeling of SN Ia explosions. Using the 2-stretch fitter, I conducted the first search for shock interactions between the exploding white dwarf and a potential companion star in the single degenerate channel. I found no evidence for shocks in an SDSS-II sample of about 100 SNe, and showed using simulations that this rules out shocks above about 9% of peak SN flux. Comparing to theoretical models of single degenerate progenitors, I rule out red giant companions and main sequence stars above 6 solar masses as common companions to SNe Ia. More recent work has focused on the effect of the SN environment, as multiple studies have shown a correlation between host galaxy mass and SN distances. The source of this mass correlation is unknown, but both metallicity and progenitor age are candidate explanations for the observed correlation. I will present new research that attempts to determine the underlying source of the mass

  20. Progenitor endothelial cell involvement in Alzheimer's disease

    SciTech Connect

    Budinger, Thomas F.

    2003-05-01

    There is compelling evidence that endothelial cells of the brain and periphery are dysfunctional in Alzheimer's Disease. There is evidence for a fundamental defect in, or abnormal aging of, endothelial progenitor cells in atherosclerosis. The possibility that endothelial cell defects are a primary cause for Alzheimer's Disease or other dementias can be researched by molecular and cell biology studies as well as cell trafficking studies using recently demonstrated molecular imaging methods. The evidence for abnormal endothelial function and the methods to explore this hypothesis are presented.

  1. The Type Ia Supernovae Progenitor Problem: Searching for Progenitors in the Milky Way

    NASA Astrophysics Data System (ADS)

    Birchall, Alexander; Di Stefano, R.; Primini, F.; Scalzo, R.

    2013-01-01

    One of the most active areas of current astrophysical research is the search for the progenitors of Type Ia supernovae. Understanding the nature(s) of the progenitors is crucial if we are to use these supernovae to conduct high-precision measurements of the history of cosmic expansion, because in order to confirm them as standardizable candles we need to understand the mechanism by which they are produced. Type Ia supernovae occur when carbon/oxygen white dwarfs explode, having gained mass either by accretion from a companion or by merging with another white dwarf. The white dwarfs in all Type Ia progenitors must go through a stage of high-rate accretion and possibly of nuclear burning. They should then be detectable as bright objects, with luminosities as high as a few times 1038 erg s-1. Furthermore, whatever the correct model(s), more than 1000 bright progenitors (and other systems that may be equally bright but in which the white dwarf does not reach the critical mass) are expected in the Milky Way. We are conducting a comprehensive search through archived data to identify unusual bright sources that may correspond to white dwarfs accreting at high rates. A significant fraction of the progenitors may appear as x-ray sources that are either supersoft or quasisoft some of the time. We have therefore searched the ROSAT, Chandra, and XMM databases to identify all such soft sources in the Milky Way that are detectable from Earth. We report on our results and their implications.

  2. Neutrino emission from nearby supernova progenitors

    NASA Astrophysics Data System (ADS)

    Yoshida, Takashi; Takahashi, Koh; Umeda, Hideyuki

    2016-05-01

    Neutrinos have an important role for energy loss process during advanced evolution of massive stars. Although the luminosity and average energy of neutrinos during the Si burning are much smaller than those of supernova neutrinos, these neutrinos are expected to be detected by the liquid scintillation neutrino detector KamLAND if a supernova explosion occurs at the distance of ~100 parsec. We investigate the neutrino emission from massive stars during advanced evolution. We calculate the evolution of the energy spectra of neutrinos produced through electron-positron pair-annihilation in the supernova progenitors with the initial mass of 12, 15, and 20 M ⊙ during the Si burning and core-collapse stages. The neutrino emission rate increases from ~ 1050 s-1 to ~ 1052 s-1. The average energy of electron-antineutrinos is about 1.25 MeV during the Si burning and gradually increases until the core-collapse. For one week before the supernova explosion, the KamLAND detector is expected to observe 12-24 and 6-13 v¯e events in the normal and inverted mass hierarchies, respectively, if a supernova explosion of a 12-20 M ⊙ star occurs at the distance of 200 parsec, corresponding to the distance to Betelgeuse. Observations of neutrinos from SN progenitors have a possibility to constrain the core structure and the evolution just before the core collapse of massive stars.

  3. Red supergiants as type II supernova progenitors

    NASA Astrophysics Data System (ADS)

    Negueruela, Ignacio; Dorda, Ricardo; González-Fernández, Carlos; Marco, Amparo

    2015-08-01

    Recent searches for supernova IIp progenitors in external galaxies have led to the identification of red objects with magnitudes and colours indicative of red supergiants, in most cases implying quite low luminosities and hence masses well below 10Msol. Stellar models, on the other hand, do not predict explosions from objects below 9 Msol. What does our knowledge of local red supergiants tells us about the expected properties of such objects?We have carried out a comprehensive spectroscopic and photometric study of a sample of hundreds of red supergiants in the Milky Way and both Magellanic Clouds. We have explored correlations between different parameters and the position of stars in the HR diagrams of open clusters. At solar metallicty, there is strong evidence for a phase of very heavy mass loss at the end of the red supergiant phase, but the existence of such a phase is still not confirmed at SMC metallicities. Objects of ~ 7Msol, on the other hand, become very dusty in the SMC, and appear as very luminous Miras.Among Milky Way clusters, we find a surprising lack of objects readily identifiable as the expected 7 to 10 Msol red supergiants or AGB stars. We are carrying out an open cluster survey aimed at filling this region of the HR diagram with reliable data. Finally, we will discuss the implications of all this findings for the expected properties of supernova progenitors, as it looks unlikely that typical red supergiants may explode without undergoing further evolution.

  4. Ventral vs. dorsal chick dermal progenitor specification.

    PubMed

    Fliniaux, Ingrid; Viallet, Jean P; Dhouailly, Danielle

    2004-01-01

    The dorsal and the ventral trunk integuments of the chick differ in their dermal cell lineage (originating from the somatic and somatopleural mesoderm respectively) and in the distribution of their feather fields. The dorsal macropattern has a large spinal pteryla surrounded by semi-apteria, whereas the ventral skin has a true medial apterium surrounded by the ventral pterylae. Comparison of the results of heterotopic transplantations of distal somatopleure in place of somatic mesoderm (Mauger 1972) or in place of proximal somatopleure (our data), leads to two conclusions. These are that the fate of the midventral apterium is not committed at day 2 of incubation and that the signals from the environment which specify the ventral and dorsal featherforming dermal progenitors are different. Effectively, Shh, but not Wnt -1 signalling can induce the formation of feather forming dermis from the embryonic somatopleure. Shh is not able, however, to trigger the formation of a feather forming dermis from the extra embryonic somatopleure. This brief report constitutes the first attempt, by comparing old and new preliminary results, to understand whether dermal progenitors at different sites are specified by different signalling pathways. PMID:15272375

  5. The progenitors of supernovae Type Ia

    NASA Astrophysics Data System (ADS)

    Toonen, Silvia

    2014-09-01

    Despite the significance of Type Ia supernovae (SNeIa) in many fields in astrophysics, SNeIa lack a theoretical explanation. SNeIa are generally thought to be thermonuclear explosions of carbon/oxygen (CO) white dwarfs (WDs). The canonical scenarios involve white dwarfs reaching the Chandrasekhar mass, either by accretion from a non-degenerate companion (single-degenerate channel, SD) or by a merger of two CO WDs (double-degenerate channel, DD). The study of SNeIa progenitors is a very active field of research for binary population synthesis (BPS) studies. The strength of the BPS approach is to study the effect of uncertainties in binary evolution on the macroscopic properties of a binary population, in order to constrain binary evolutionary processes. I will discuss the expected SNeIa rate from the BPS approach and the uncertainties in their progenitor evolution, and compare with current observations. I will also discuss the results of the POPCORN project in which four BPS codes were compared to better understand the differences in the predicted SNeIa rate of the SD channel. The goal of this project is to investigate whether differences in the simulated populations are due to numerical effects or whether they can be explained by differences in the input physics. I will show which assumptions in BPS codes affect the results most and hence should be studied in more detail.

  6. Type Ia Progenitor Hunt in Ancient Remnants

    NASA Astrophysics Data System (ADS)

    Kerzendorf, Wolfgang E.

    2013-01-01

    There is broad agreement that the stars which explode as Type Ia supernovae are white dwarfs. They have accreted material in a binary system until they are near the Chandrasekhar mass and detonate/deflagrate. The two main scenarios for this accretion process are merging with a companion white dwarf (double degenerate scenario), or accretion from a main-sequence to red giant donor (single degenerate scenario). The donor star survives post-explosion and would provide substantial evidence for the single degenerate scenario, if found. Our team is analyzing stars in close proximity to Galactic Type Ia remnants to find surviving donor stars. In my talk I will introduce the different progenitor systems and the expected state for a donor star today. I will outline our search using high resolution spectroscopy and will present updated results.

  7. Progenitor model of cosmic ray knee

    NASA Astrophysics Data System (ADS)

    Bijay, Biplab; Bhadra, Arunava

    2016-01-01

    The primary energy spectrum of cosmic rays exhibits a knee at about 3 PeV where a change in the spectral index occurs. Despite many efforts, the origin of such a feature in the spectrum is not satisfactorily solved yet. Here it is proposed that the steepening of the spectrum beyond the knee may be a consequence of the mass distribution of the progenitor of the cosmic ray source. The proposed speculative model can account for all the major observed features of cosmic rays without invoking any fine tuning to match flux or spectra at any energy point. The prediction of the proposed model regarding the primary composition scenario beyond the knee is quite different from most of the prevailing models of the knee, and thereby can be discriminated from precise experimental measurement of the primary composition.

  8. New approaches to SNe Ia progenitors

    NASA Astrophysics Data System (ADS)

    Ruiz-Lapuente, Pilar

    2014-10-01

    Although Type Ia supernovae (SNe Ia) are a major tool in cosmology and play a key role in the chemical evolution of galaxies, the nature of their progenitor systems (apart from the fact that they must content at least one white dwarf, that explodes) remains largely unknown. In the last decade, considerable efforts have been made, both observationally and theoretically, to solve this problem. Observations have, however, revealed a previously unsuspected variety of events, ranging from very underluminous outbursts to clearly overluminous ones, and spanning a range well outside the peak luminosity-decline rate of the light curve relationship, used to make calibrated candles of the SNe Ia. On the theoretical side, new explosion scenarios, such as violent mergings of pairs of white dwarfs, have been explored. We review those recent developments, emphasizing the new observational findings, but also trying to tie them to the different scenarios and explosion mechanisms proposed thus far.

  9. Multipotent pancreas progenitors: Inconclusive but pivotal topic.

    PubMed

    Jiang, Fang-Xu; Morahan, Grant

    2015-12-26

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  10. PET imaging of adoptive progenitor cell therapies.

    SciTech Connect

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  11. Multipotent pancreas progenitors: Inconclusive but pivotal topic

    PubMed Central

    Jiang, Fang-Xu; Morahan, Grant

    2015-01-01

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  12. Galaxies, their satellites and progenitors: chemical properties

    NASA Astrophysics Data System (ADS)

    Gargiulo, I.; Cora, S. A.; Padilla, N. D.

    We use a model that combines N-body cosmological simulations of galaxy clusters and a semi-analytic model of galaxy formation (SAG: Semi-analytical galaxies; Lagos, Cora & Padilla, 2008) in order to study the properties of galaxy progenitors, using the information provided by their stellar haloes, and surviving satellites at redshift z = 0. We model the formation of stellar haloes by considering tidal stripping events acting on the satellite galaxies before the mergers occur, being able to follow their mass, luminosity and chemical properties. We find that the satellite galaxies have lower metal- licities than the stellar haloes of central galaxies for a given host DM halo mass, as has been already noted by Lagos, Padilla & Cora (2009), using a different approach.

  13. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals

    PubMed Central

    Mead, Laura E.; Prater, Daniel; Krier, Theresa R.; Mroueh, Karim N.; Li, Fang; Krasich, Rachel; Temm, Constance J.; Prchal, Josef T.

    2007-01-01

    The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies “endothelial cell colony-forming units” (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration. PMID:17053059

  14. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.

    PubMed

    Yoder, Mervin C; Mead, Laura E; Prater, Daniel; Krier, Theresa R; Mroueh, Karim N; Li, Fang; Krasich, Rachel; Temm, Constance J; Prchal, Josef T; Ingram, David A

    2007-03-01

    The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration. PMID:17053059

  15. A COMPREHENSIVE PROGENITOR MODEL FOR SNe Ia

    SciTech Connect

    Meng, X.; Yang, W.

    2010-02-20

    Although the nature of the progenitor of Type Ia supernovae (SNe Ia) is still unclear, the single-degenerate (SD) channel for the progenitor is currently accepted, in which a carbon-oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion, increases its mass to the Chandrasekhar mass limit, and then explodes as an SN Ia. The companion may be a main sequence or a slightly evolved star (WD + MS), or a red giant star (WD + RG). Incorporating the effect of mass stripping and accretion-disk instability on the evolution of the WD binary, we carried out binary stellar evolution calculations for more than 1600 close WD binaries. As a result, the initial parameter spaces for SNe Ia are presented in an orbital period-secondary mass (log P{sub i}, M {sup i}{sub 2}) plane. We confirmed that in a WD + MS system, the initial companion leading to SNe Ia may have mass from 1 M{sub sun} to 5 M{sub sun}. The initial WD mass for SNe Ia from WD + MS channel is as low as 0.565 M{sub sun}, while the lowest WD mass from the WD + RG channel is 1.0 M{sub sun}. Adopting the above results, we studied the birth rate of SNe Ia via a binary population synthesis approach. We found that the Galactic SNe Ia birth rate from SD model is (2.55-2.9) x 10{sup -3} yr{sup -1} (including WD + He star channel), which is slightly smaller than that from observation. If a single starburst is assumed, the distribution of the delay time of SNe Ia from the SD model may be a weak bimodality, where WD + He channel contributes to SNe Ia with delay time shorter than 10{sup 8} yr and WD + RG channel to those with age longer than 6 Gyr.

  16. The dynamics of murine mammary stem/progenitor cells

    PubMed Central

    DONG, Qiaoxiang; SUN, Lu-Zhe

    2014-01-01

    The stem/progenitor cells in the murine mammary gland are a highly dynamic population of cells that are responsible for ductal elongation in puberty, homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy. In recent years understanding the epithelial cell hierarchy within the mammary gland is becoming particularly important as these different stem/progenitor cells were perceived to be the cells of origin for various subtypes of breast cancer. Although significant advances have been made in enrichment and isolation of stem/progenitor cells by combinations of antibodies against cell surface proteins together with flow cytometry, and in identification of stem/progenitor cells with multi-lineage differentiation and self-renewal using mammary fat pad reconstitution assay and in vivo genetic labeling technique, a clear understanding of how these different stem/progenitors are orchestrated in the mammary gland is still lacking. Here we discuss the different in vivo and in vitro methods currently available for stem/progenitor identification, their associated caveats, and a possible new hierarchy model to reconcile various putative stem/progenitor cell populations identified by different research groups. PMID:25580105

  17. Caspase-1 mediates hyperlipidemia-weakened progenitor cell vessel repair

    PubMed Central

    Li, Ya-Feng; Huang, Xiao; Li, Xinyuan; Gong, Ren; Yin, Ying; Nelson, Jun; Gao, Erhe; Zhang, Hongyu; Hoffman, Nicholas E.; Houser, Steven R.; Madesh, Muniswamy; Tilley, Douglas G.; Choi, Eric T.; Jiang, Xiaohua; Huang, Cong-Xin; Wang, Hong; Yang, Xiao-Feng

    2015-01-01

    Caspase-1 activation senses metabolic danger-associated molecular patterns (DAMPs) and mediates the initiation of inflammation in endothelial cells. Here, we examined whether the caspase-1 pathway is responsible for sensing hyperlipidemia as a DAMP in bone marrow (BM)-derived Stem cell antigen-1 positive (Sca-1+) stem/progenitor cells and weakening their angiogenic ability. Using biochemical methods, gene knockout, cell therapy and myocardial infarction (MI) models, we had the following findings: 1) Hyperlipidemia induces caspase-1 activity in mouse Sca-1+ progenitor cells in vivo; 2) Caspase-1 contributes to hyperlipidemia-induced modulation of vascular cell death-related gene expression in vivo; 3) Injection of Sca-1+ progenitor cells from caspase-1−/− mice improves endothelial capillary density in heart and decreases cardiomyocyte death in a mouse model of MI; and 4) Caspase-1−/− Sca-1+ progenitor cell therapy improves mouse cardiac function after MI. Our results provide insight on how hyperlipidemia activates caspase-1 in Sca-1+ progenitor cells, which subsequently weakens Sca-1+ progenitor cell repair of vasculature injury. These results demonstrate the therapeutic potential of caspase-1 inhibition in improving progenitor cell therapy for MI. PMID:26709768

  18. Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

    PubMed

    Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

    2012-09-01

    Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. PMID:22497336

  19. PDL Progenitor-Mediated PDL Recovery Contributes to Orthodontic Relapse.

    PubMed

    Feng, L; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; He, D; Gan, Y; Kou, X; Zhou, Y

    2016-08-01

    Periodontal ligament (PDL) is subjected to mechanical force during physiologic activities. PDL stem /: progenitor cells are the main mesenchymal stem cells in PDL. However, how PDL progenitors participate in PDL homeostasis upon and after mechanical force is largely unknown. In this study, force-triggered orthodontic tooth movement and the following relapse were used as models to demonstrate the response of PDL progenitors and their role in PDL remodeling upon and after mechanical force. Upon orthodontic force, PDL collagen on the compression side significantly degraded, showing a broken and disorganized pattern. After force withdrawal, the degraded PDL collagen recovered during the early stage of relapse. Correspondingly, increased CD90(+) PDL progenitors with suppressed expression of type I collagen (Col-I) were observed upon orthodontic force, whereas these cells accumulated at the degradation regions and regained Col-I expression after force withdrawal during early relapse. Our results further showed that compressive force altered cell morphology and repressed collagen expression in cultured PDL progenitors, which both recovered after force withdrawal. Force withdrawal-induced recovery of collagen expression in cultured PDL progenitors could be regulated by transforming growth factor-β (TGF-β), a key molecule for tissue homeostasis and extracellular matrix remodeling. More interesting, inhibiting the regained Col-I expression in CD90(+) PDL progenitors by blocking TGF-β interrupted PDL collagen recovery and partially inhibited the early relapse. These data suggest that PDL progenitors can respond to mechanical force and may process intrinsic stability to recover to original status after force withdrawal. PDL progenitors with intrinsic stability are required for PDL recovery and consequently contribute to early orthodontic relapse, which can be regulated by TGF-β signaling. PMID:27161015

  20. First description of B chromosomes in the family Auchenipteridae, Parauchenipterus galeatus (Siluriformes) of the São Francisco River basin (MG, Brazil).

    PubMed

    Lui, Roberto Laridondo; Blanco, Daniel Rodrigues; Margarido, Vladimir Pavan; Filho, Orlando Moreira

    2009-01-01

    B chromosomes are considered additional and non-essential; they likely originate from A chromosomes and follow a distinct evolution. In fish, approximately half of the Neotropical species with B chromosomes are Characiformes and 35% are Siluriformes. There has been no report of B chromosomes in Auchenipteridae until this moment. B chromosomes found in a population of Parauchenipterus galeatus from the São Francisco River basin in the state of Minas Gerais (Brazil) were small, metacentric, totally heterochromatic and exhibited intra-individual and inter-individual variation. The diploid number was 58 chromosomes (22 metacentric, 16 submetacentric, 12 subtelocentric and 8 acrocentric). The nucleolar organizing regions were simple and the heterochromatin intercalated in the ribosomal sites, characterized by CMA(3) and DAPI fluorochromes, was of a GC-rich constitution. The 5S rDNA genes were located in an intercalary position in only one chromosome pair. An hypothesis about the origin of the B chromosomes in P. galeatus and a review on B chromosomes in catfish are also presented in this study. PMID:19394233

  1. A new Neocalceostomatid (Monogenoidea) from the gills of the blackfin sea catfish, Arius jella (Siluriformes: Ariidae), in the Bay of Bengal, India.

    PubMed

    Kritsky, Delane C; Shameem, U; Kumari, Ch Padma; Krishnaveni, I

    2012-06-01

    Thysanotohaptor n. gen. (Neocalceostomatidae) is proposed to accommodate Thysanotohaptor rex n. sp. collected from the gills of the blackfin sea catfish Arius jella Day (Siluriformes: Ariidae) from off the coast of Visakhapatnam, Bay of Bengal, Andhra Pradesh, India. Thysanotohaptor is differentiated from the other known neocalceostomatid genera by its species having multiple postgermarial testes (single testis in species of Neocalceostoma and Neocalceostomoides ), lacking a transverse bar associated with the ventral anchor pair (present in species of Neocalceostoma ), and possessing a disc-shaped haptor with a pleated marginal frill (frill absent in Neocalceostomoides spp.; Neocalceostoma spp. with delicate marginal membranes). The Neocalceostomatidae is considered valid within the Order Dactylogyridea based on its members having a haptor armed with 10 marginal and 4 ventral hooks and a germarium having a distal loop prior to uniting with the ootype; the family is not assigned to a suborder of Dactylogyridea because of uncertainty in part about the way in which the distribution of haptoral hooks evolved within the taxon. PMID:22263751

  2. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.

    PubMed

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir; Jaitin, Diego Adhemar; Kenigsberg, Ephraim; Keren-Shaul, Hadas; Winter, Deborah; Lara-Astiaso, David; Gury, Meital; Weiner, Assaf; David, Eyal; Cohen, Nadav; Lauridsen, Felicia Kathrine Bratt; Haas, Simon; Schlitzer, Andreas; Mildner, Alexander; Ginhoux, Florent; Jung, Steffen; Trumpp, Andreas; Porse, Bo Torben; Tanay, Amos; Amit, Ido

    2015-12-17

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory mechanisms. Here, we comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution. PMID:26627738

  3. Stem and progenitor cell dysfunction in human trisomies

    PubMed Central

    Liu, Binbin; Filippi, Sarah; Roy, Anindita; Roberts, Irene

    2015-01-01

    Trisomy 21, the commonest constitutional aneuploidy in humans, causes profound perturbation of stem and progenitor cell growth, which is both cell context dependent and developmental stage specific and mediated by complex genetic mechanisms beyond increased Hsa21 gene dosage. While proliferation of fetal hematopoietic and testicular stem/progenitors is increased and may underlie increased susceptibility to childhood leukemia and testicular cancer, fetal stem/progenitor proliferation in other tissues is markedly impaired leading to the characteristic craniofacial, neurocognitive and cardiac features in individuals with Down syndrome. After birth, trisomy 21-mediated premature aging of stem/progenitor cells may contribute to the progressive multi-system deterioration, including development of Alzheimer's disease. PMID:25520324

  4. Murine Hematopoietic Stem cells and Progenitors Express Adrenergic Receptors

    PubMed Central

    Muthu, Kuzhali; Iyer, Sivaraman; He, L-K.; Szilagyi, Andrea; Gamelli, Richard L; Shankar, Ravi; Jones, Stephen B

    2007-01-01

    Association between the nervous and immune system is well documented. Immune cells originate within the bone marrow that is innervated. Thermal injury induces adrenergic stimulation, augments monocytopoiesis and alters the β-adrenergic receptor (AR) profile of bone marrow monocyte committed progenitors. This provides an impetus to study AR expression in hematopoietic progenitors along myeloid lineage. Using FACS analysis and confocal microscopy, we report the expression of α1-, α2- and β2- AR in enriched populations of ER-MP20+ and ER-MP12+ myeloid progenitors, CD117+ and CD34+ multi-potential progenitors and more importantly pluripotent stem cells suggesting a plausible role for catecholamine in hematopoietic development. PMID:17428548

  5. Signaling pathways implicated in hematopoietic progenitor cell proliferation and differentiation.

    PubMed

    Bugarski, Diana; Krstic, Aleksandra; Mojsilovic, Slavko; Vlaski, Marija; Petakov, Marijana; Jovcic, Gordana; Stojanovic, Nevenka; Milenkovic, Pavle

    2007-01-01

    The objective of this study was to investigate the signal transduction pathways associated with the clonal development of myeloid and erythroid progenitor cells. The contribution of particular signaling molecules of protein tyrosine kinases (PTKs), mitogen-activated protein (MAP) kinase, and PI-3 kinase signaling to the growth of murine bone marrow colony forming unit-granulocyte-macrophage (CFU-GM) and erythroid (burst forming unit-erythroid [BFU-E] and colony forming unit-erythroid [CFU-E]) progenitors was examined in studies performed in the presence or absence of specific signal transduction inhibitors. The results clearly pointed to different signal transducing intermediates that are involved in cell proliferation and differentiation depending on the cell lineage, as well as on the progenitors' maturity. Lineage-specific differences were obtained when chemical inhibitors specific for receptor- or nonreceptor-PTKs, as well as for the main groups of distinctly regulated MAPK cascades, were used because all of these compounds suppressed the growth of erythroid progenitors, with no major effects on myeloid progenitors. At the same time, differential involvement of MEK/extracellular signal-regulated kinase (ERK) MAPK transduction pathway was observed in the proliferation and/or differentiation of early, BFU-E, and late, CFU-E, erythroid progenitor cells. The results also demonstrated that phosphatydylinositol (PI)-3 kinase and nuclear factor kappaB (NF-kappaB) transcriptional factor were required for maintenance of both myeloid and erythroid progenitor cell function. Overall, the data obtained indicated that committed hematopoietic progenitors express a certain level of constitutive signaling activity that participates in the regulation of normal steady-state hematopoiesis and point to the importance of evaluating the impact of signal transduction inhibitors on normal bone marrow when used as potential therapeutic agents. PMID:17202596

  6. Harnessing endogenous stem/progenitor cells for tendon regeneration

    PubMed Central

    Lee, Chang H.; Lee, Francis Y.; Tarafder, Solaiman; Kao, Kristy; Jun, Yena; Yang, Guodong; Mao, Jeremy J.

    2015-01-01

    Current stem cell–based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues. PMID:26053662

  7. Viral disruption of olfactory progenitors is exacerbated in allergic mice.

    PubMed

    Ueha, R; Mukherjee, S; Ueha, S; de Almeida Nagata, D E; Sakamoto, T; Kondo, K; Yamasoba, T; Lukacs, N W; Kunkel, S L

    2014-09-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP(+) mature ORNs and SOX2(+) ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2(+) ORN progenitors without affecting OMP(+) ORNs. In contrast, the RSV-induced decrease in SOX2(+) ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP(+) ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance. PMID:24998164

  8. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus.

    PubMed

    Li, Yu-Qing; Cheng, Zoey; Wong, Shun

    2016-01-01

    Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation. PMID:27331809

  9. LINKING TYPE Ia SUPERNOVA PROGENITORS AND THEIR RESULTING EXPLOSIONS

    SciTech Connect

    Foley, Ryan J.; Kirshner, Robert P.; Simon, Joshua D.; Burns, Christopher R.; Gal-Yam, Avishay; Hamuy, Mario; Morrell, Nidia I.; Phillips, Mark M.; Shields, Gregory A.; Sternberg, Assaf

    2012-06-20

    Comparing the ejecta velocities at maximum brightness and narrow circumstellar/interstellar Na D absorption line profiles of a sample of 23 Type Ia supernovae (SNe Ia), we determine that the properties of SN Ia progenitor systems and explosions are intimately connected. As demonstrated by Sternberg et al., half of all SNe Ia with detectable Na D absorption at the host-galaxy redshift in high-resolution spectroscopy have Na D line profiles with significant blueshifted absorption relative to the strongest absorption component, which indicates that a large fraction of SN Ia progenitor systems have strong outflows. In this study, we find that SNe Ia with blueshifted circumstellar/interstellar absorption systematically have higher ejecta velocities and redder colors at maximum brightness relative to the rest of the SN Ia population. This result is robust at a 98.9%-99.8% confidence level, providing the first link between the progenitor systems and properties of the explosion. This finding is further evidence that the outflow scenario is the correct interpretation of the blueshifted Na D absorption, adding additional confirmation that some SNe Ia are produced from a single-degenerate progenitor channel. An additional implication is that either SN Ia progenitor systems have highly asymmetric outflows that are also aligned with the SN explosion or SNe Ia come from a variety of progenitor systems where SNe Ia from systems with strong outflows tend to have more kinetic energy per unit mass than those from systems with weak or no outflows.

  10. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    PubMed Central

    Li, Yu-Qing; Cheng, Zoey; Wong, Shun

    2016-01-01

    Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation. PMID:27331809

  11. How Low Can They Go? Detecting low luminosity supernova progenitors

    NASA Astrophysics Data System (ADS)

    Fruchter, Andrew

    2013-10-01

    While we now discover thousands of supernovae {SNe} per year, in the history of astronomy a little more than a dozen SN progenitors have been identified, and all of these have been from Type II SNe. This dearth is largely due to the fact that the progenitors are destroyed in the SN, and so to study them one must have fortuitously taken data on them prior to their explosion. However, the fault may also partially lie with the methods employed to search for progenitors.In the past, searches have generally relied on looking at the location of a SNe in an archival image to see if a noticeable point source is at the right location. This method requires that the background field of the galaxy be relatively uniform, and if one wants an accurate estimate of the progenitor mangitude, that the star was not in an association or binary. Here we propose to take WFC3 images several years post explosion so that we can subtract them from archival WFPC2 images. We show that we can do this with extraordinary fidelity. We will apply this method to a well-chosen sample of three Type II SNe and two Type Ibc SNe, which lie on messy galaxy fields that may have camouflaged the presence of a progenitor. This method has the potential to detect or substantially deepen the limits on the progenitors of these objects, which already appear too faint for theoretical models.

  12. Possible Progenitor of Special Supernova Type Detected

    NASA Astrophysics Data System (ADS)

    2008-04-01

    caused by material being pulled off a companion star onto the white dwarf, fusion of this material on the surface of the star should heat the star and produce a strong source of X-radiation prior to the explosion. Once the supernova explosion occurs, the white dwarf is expected to be completely destroyed and then would be undetectable in X-rays. In the merger scenario, the intensity of X-ray emission prior to the explosion is expected to be much weaker. Based on the detection of a fairly strong X-ray source at approximately the position of SN 2007on 4 years before the explosion, Voss and Nelemans conclude that the data support the scenario where matter is pulled off a companion star. The small number of X-ray sources in the field implies that there is only a small chance of an unrelated source being so close by coincidence. Also, the X-ray source has similar properties to those expected for fusion on a white dwarf, unlike most X-ray sources in the sky. However, in follow-up studies, Voss, Nelemans and colleagues Gijs Roelofs (Harvard-Smithsonian Center for Astrophysics, Cambridge, Mass.) and Cees Bassa (McGill University, Canada) used higher-quality optical images to better determine the supernova's position. This work, which is not yet published, shows a small, but significant difference in the measured positions of the supernova and the X-ray source, suggesting the source may not be the progenitor. Follow-up Chandra observations hint that the X-ray object has disappeared, but further observations are needed to finally decide whether the source was the progenitor or not. The team is also applying this new method to other supernovas and has high hopes that they will eventually succeed in identifying the elusive cause of at least some of these explosions. "We're very excited about opening up a new way of studying supernovas, even though we're not sure that we've seen this particular stellar bomb before it exploded," said Gijs Roelofs. "We're very confident that we

  13. NFAT restricts osteochondroma formation from entheseal progenitors

    PubMed Central

    Ge, Xianpeng; Tsang, Kelly; He, Lizhi; Garcia, Roberto A.; Ermann, Joerg; Mizoguchi, Fumitaka; Zhang, Minjie; Zhou, Bin; Zhou, Bin; Aliprantis, Antonios O.

    2016-01-01

    Osteochondromas are common benign osteocartilaginous tumors in children and adolescents characterized by cartilage-capped bony projections on the surface of bones. These tumors often cause pain, deformity, fracture, and musculoskeletal dysfunction, and they occasionally undergo malignant transformation. The pathogenesis of osteochondromas remains poorly understood. Here, we demonstrate that nuclear factor of activated T cells c1 and c2 (NFATc1 and NFATc2) suppress osteochondromagenesis through individual and combinatorial mechanisms. In mice, conditional deletion of NFATc1 in mesenchymal limb progenitors, Scleraxis-expressing (Scx-expressing) tendoligamentous cells, or postnatally in Aggrecan-expressing cells resulted in osteochondroma formation at entheses, the insertion sites of ligaments and tendons onto bone. Combinatorial deletion of NFATc1 and NFATc2 gave rise to larger and more numerous osteochondromas in inverse proportion to gene dosage. A population of entheseal NFATc1- and Aggrecan-expressing cells was identified as the osteochondroma precursor, previously believed to be growth plate derived or perichondrium derived. Mechanistically, we show that NFATc1 restricts the proliferation and chondrogenesis of osteochondroma precursors. In contrast, NFATc2 preferentially inhibits chondrocyte hypertrophy and osteogenesis. Together, our findings identify and characterize a mechanism of osteochondroma formation and suggest that regulating NFAT activity is a new therapeutic approach for skeletal diseases characterized by defective or exaggerated osteochondral growth. PMID:27158674

  14. Cardiogenic Differentiation and Transdifferentiation of Progenitor Cells

    PubMed Central

    Reinecke, Hans; Minami, Elina; Zhu, Wei-Zhong; Laflamme, Michael A.

    2009-01-01

    In recent years, cell transplantation has drawn tremendous interest as a novel approach to preserving or even restoring contractile function to infarcted hearts. A typical human infarct involves the loss of approximately one billion cardiomyocytes, and so many investigators have sought to identify endogenous or exogenous stem cells with the capacity to differentiate into committed cardiomyocytes and repopulate lost myocardium. As a result of these efforts, dozens of stem cell types have been reported to have cardiac potential. These include pluripotent embryonic stem cells as well various adult stem cells resident in compartments including bone marrow, peripheral tissues, and the heart itself. Some of these cardiogenic progenitors have been reported to contribute replacement muscle through endogenous reparative processes or via cell transplantation in preclinical cardiac injury models. However, considerable disagreement exists regarding the efficiency and even the reality of cardiac differentiation by many of these stem cell types, making these issues a continuing source of controversy in the field. In this review, we consider approaches to cell fate mapping and establishing the cardiac phenotype, as well as the current state of the evidence for the cardiogenic and regenerative potential of the major candidate stem cell types. PMID:18988903

  15. Role of liver progenitors in liver regeneration

    PubMed Central

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A.

    2015-01-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs. PMID:25713804

  16. TWEAK induces liver progenitor cell proliferation.

    PubMed

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M; Wang, Monica Z; Zheng, Timothy S; Browning, Beth; Michaelson, Jennifer S; Baetscher, Manfred; Baestcher, Manfred; Wang, Bruce; Bissell, D Montgomery; Burkly, Linda C

    2005-09-01

    Progenitor ("oval") cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  17. Type Ia Supernova Models and Progenitor Scenarios

    NASA Astrophysics Data System (ADS)

    Nomoto, Ken'ichi; Kamiya, Yasuomi; Nakasato, Naohito

    2013-01-01

    We review some recent developments in theoretical studies on the connection between the progenitor systems of Type Ia supernovae (SNe Ia) and the explosion mechanisms. (1) DD-subCh: In the merging of double C+O white dwarfs (DD scenario), if the carbon detonation is induced near the white dwarf (WD) surface in the early dynamical phase, it could result in the (effectively) sub-Chandrasekhar mass explosion. (2) DD-Ch: If no surface C-detonation is ignited, the WD could grow until the Chandrasekhar mass is reached, but the outcome depends on whether the quiescent carbon shell burning is ignited and burns C+O into O+Ne+Mg. (3) SD-subCh: In the single degenerate (SD) scenario, if the He shell-flashes grow strong to induce a He detonation, it leads to the sub-Chandra explosion. (4) SD-Ch: If the He-shell flashes are not strong enough, they still produce interesting amounts of Si and S near the surface of the C+O WD before the explosion. In the Chandra mass explosion, the central density is high enough to produce electron capture elements, e.g., stable 58Ni. Observations of the emission lines of Ni in the nebular spectra provides useful diagnostics of the sub-Chandra vs. Chandra issue. The recent observations of relatively low velocity carbon near the surface of SNe Ia provide also an interesting constraint on the explosion models.

  18. The Binary Progenitor of Tycho Brahe's Supernova

    NASA Astrophysics Data System (ADS)

    Ruiz-Lapuente, P.

    2006-08-01

    The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova (SN 1572) provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.

  19. Cell-Surface Protein Profiling Identifies Distinctive Markers of Progenitor Cells in Human Skeletal Muscle.

    PubMed

    Uezumi, Akiyoshi; Nakatani, Masashi; Ikemoto-Uezumi, Madoka; Yamamoto, Naoki; Morita, Mitsuhiro; Yamaguchi, Asami; Yamada, Harumoto; Kasai, Takehiro; Masuda, Satoru; Narita, Asako; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Fukada, So-Ichiro; Nishino, Ichizo; Tsuchida, Kunihiro

    2016-08-01

    Skeletal muscle contains two distinct stem/progenitor populations. One is the satellite cell, which acts as a muscle stem cell, and the other is the mesenchymal progenitor, which contributes to muscle pathogeneses such as fat infiltration and fibrosis. Detailed and accurate characterization of these progenitors in humans remains elusive. Here, we performed comprehensive cell-surface protein profiling of the two progenitor populations residing in human skeletal muscle and identified three previously unrecognized markers: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers distinguish myogenic and mesenchymal progenitors, and enable efficient isolation of the two types of progenitors. Functional study revealed that CD82 ensures expansion and preservation of myogenic progenitors by suppressing excessive differentiation, and CD201 signaling favors adipogenesis of mesenchymal progenitors. Thus, cell-surface proteins identified here are not only useful markers but also functionally important molecules, and provide valuable insight into human muscle biology and diseases. PMID:27509136

  20. Circulating Hematopoietic Progenitor Cells are Decreased in COPD

    PubMed Central

    Janssen, William J.; Yunt, Zulma X.; Muldrow, Alaina; Kearns, Mark T.; Kloepfer, Angela; Barthel, Lea; Bratton, Donna L.; Bowler, Russell P.; Henson, Peter M.

    2014-01-01

    Rationale Bone marrow derived progenitor cells participate in the repair of injured vessels. The lungs of individuals with emphysema have reduced alveolar capillary density and increased endothelial apoptosis. We hypothesized that circulating levels of endothelial and hematopoietic progenitor cells would be reduced in this group of patients. Objectives The goal of this study was to measure circulating levels of endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) in subjects with COPD and to determine if progenitor levels correlated with disease severity and the presence of emphysema. Methods Peripheral blood mononuclear cells were isolated from 61 patients with COPD and 32 control subjects. Levels of EPCs (CD45dim CD34+ ) and HPCs (CD45+ CD34+ VEGF-R2+) were quantified using multi-parameter flow cytometry. Progenitor cell function was assessed using cell culture assays. All subjects were evaluated with spirometry and CT scanning. Measurements and Main Results HPC levels were reduced in subjects with COPD compared to controls, whereas circulating EPC levels were similar between the two groups. HPC levels correlated with severity of obstruction and were lowest in subjects with severe emphysema. These associations remained after correction for factors known to affect progenitor cell levels including age, smoking status, the use of statin medications and the presence of coronary artery disease. The ability of mononuclear cells to form endothelial cell colony forming units (EC-CFU) was also reduced in subjects with COPD. Conclusions HPC levels are reduced in subjects with COPD and correlate with emphysema phenotype and severity of obstruction. Reduction of HPCs may disrupt maintenance of the capillary endothelium, thereby contributing to the pathogenesis of COPD. PMID:24182349

  1. Molecular assembly of botulinum neurotoxin progenitor complexes.

    PubMed

    Benefield, Desirée A; Dessain, Scott K; Shine, Nancy; Ohi, Melanie D; Lacy, D Borden

    2013-04-01

    Botulinum neurotoxin (BoNT) is produced by Clostridium botulinum and associates with nontoxic neurotoxin-associated proteins to form high-molecular weight progenitor complexes (PCs). The PCs are required for the oral toxicity of BoNT in the context of food-borne botulism and are thought to protect BoNT from destruction in the gastrointestinal tract and aid in absorption from the gut lumen. The PC can differ in size and protein content depending on the C. botulinum strain. The oral toxicity of the BoNT PC increases as the size of the PC increases, but the molecular architecture of these large complexes and how they contribute to BoNT toxicity have not been elucidated. We have generated 2D images of PCs from strains producing BoNT serotypes A1, B, and E using negative stain electron microscopy and single-particle averaging. The BoNT/A1 and BoNT/B PCs were observed as ovoid-shaped bodies with three appendages, whereas the BoNT/E PC was observed as an ovoid body. Both the BoNT/A1 and BoNT/B PCs showed significant flexibility, and the BoNT/B PC was documented as a heterogeneous population of assembly/disassembly intermediates. We have also determined 3D structures for each serotype using the random conical tilt approach. Crystal structures of the individual proteins were placed into the BoNT/A1 and BoNT/B PC electron density maps to generate unique detailed models of the BoNT PCs. The structures highlight an effective platform that can be engineered for the development of mucosal vaccines and the intestinal absorption of oral biologics. PMID:23509303

  2. [Umbilical cord hematopoietic progenitor cells bank].

    PubMed

    Morales, V H; Milone, J; Etchegoyen, O; Bordone, J; Uranga, A

    2001-01-01

    Transplantation of hematopoietic progenitor cells (HPC) from bone marrow and mobilized peripheral blood is a standard therapy in malignant and non malignant diseases. The lack of suitable donors is an important limitation. The discovery that umbilical cord blood (CB) contains high numbers of HPC that can be used as an alternative source for allogeneic stem cell transplantation led ITMO to establish BANCEL, the first Argentine and Latinoamerican experience of its kind. The blood remaining in the umbilical cord and in the placenta was requested from women who were in the last quarter of pregnancy. An informed consent together with a medical record focused on family disease was completed. Out of 65 donations, 55 (85%) were collected and 51 (78%) were cryopreserved. Mean collected volume was 110 ml with 68% (75 ml) reduction and mean cryopreservation of 35 ml; ABO and Rh blood group systems were determined, HLA, class I, A and B loci, and class II, DR locus were typed by molecular biology methods using PCR-SSOP. Infectious disease screening was carried out for brucellosis, syphilis, Chagas, hepatitis B and C, HIV I and II, HTLV I and II, toxoplasmosis and cytomegalovirus. Two positive units for hepatitis B (anticore) and two positive units for Chagas were discarded. The quantity of total nucleated cells (TNC), CD34+ cells and the clonogenic capacity were determined twice at the collection and after the procedures of volume reduction previous to cryopreservation. A 5% reduction in both TNC and CD34 cells and a 10% in the colony forming units (CFU) were detected. A good correlation coefficient between TNC and CFU was obtained. PMID:11808425

  3. Endothelial Progenitor Cells in Diabetic Retinopathy

    PubMed Central

    Lois, Noemi; McCarter, Rachel V.; O’Neill, Christina; Medina, Reinhold J.; Stitt, Alan W.

    2014-01-01

    Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40–50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication. PMID:24782825

  4. MY Camelopardalis, a very massive merger progenitor

    NASA Astrophysics Data System (ADS)

    Lorenzo, J.; Negueruela, I.; Baker, A. K. F. Val; García, M.; Simón-Díaz, S.; Pastor, P.; Méndez Majuelos, M.

    2014-12-01

    Context. The early-type binary MY Cam belongs to the young open cluster Alicante 1, embedded in Cam OB3. Aims: MY Cam consists of two early-O type main-sequence stars and shows a photometric modulation suggesting an orbital period slightly above one day. We intend to confirm this orbital period and derive orbital and stellar parameters. Methods: Timing analysis of a very exhaustive (4607 points) light curve indicates a period of 1.1754514 ± 0.0000015 d. High-resolution spectra and the cross-correlation technique implemented in the todcor program were used to derive radial velocities and obtain the corresponding radial velocity curves for MY Cam. Modelling with the stellar atmosphere code fastwind was used to obtain stellar parameters and create templates for cross-correlation. Stellar and orbital parameters were derived using the Wilson-Devinney code, such that a complete solution to the binary system could be described. Results: The determined masses of the primary and secondary stars in MY Cam are 37.7 ± 1.6 and 31.6 ± 1.4M⊙, respectively. The corresponding temperatures, derived from the model atmosphere fit, are 42 000 and 39 000 K, with the more massive component being hotter. Both stars are overfilling their Roche lobes, sharing a common envelope. Conclusions: MY Cam contains the most massive dwarf O-type stars found so far in an eclipsing binary. Both components are still on the main sequence, and probably not far from the zero-age main sequence. The system is a likely merger progenitor, owing to its very short period. Tables 1 and 3 are available in electronic form at http://www.aanda.orgPhotometric data (Table 2) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/572/A110

  5. Endothelial progenitor cells in acute ischemic stroke

    PubMed Central

    Martí-Fàbregas, Joan; Crespo, Javier; Delgado-Mederos, Raquel; Martínez-Ramírez, Sergi; Peña, Esther; Marín, Rebeca; Dinia, Lavinia; Jiménez-Xarrié, Elena; Fernández-Arcos, Ana; Pérez-Pérez, Jesús; Querol, Luis; Suárez-Calvet, Marc; Badimon, Lina

    2013-01-01

    Objectives The levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points. Material and methods We studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0–2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry. Results We included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes. Conclusions After acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months. PMID:24363968

  6. Development and molecular composition of the hepatic progenitor cell niche.

    PubMed

    Vestentoft, Peter Siig

    2013-05-01

    End-stage liver diseases represent major health problems that are currently treated by liver transplantation. However, given the world-wide shortage of donor livers novel strategies are needed for therapeutic treatment. Adult stem cells have the ability to self-renew and differentiate into the more specialized cell types of a given organ and are found in tissues throughout the body. These cells, whose progeny are termed progenitor cells in human liver and oval cells in rodents, have the potential to treat patients through the generation of hepatic parenchymal cells, even from the patient's own tissue. Little is known regarding the nature of the hepatic progenitor cells. Though they are suggested to reside in the most distal part of the biliary tree, the canal of Hering, the lack of unique surface markers for these cells has hindered their isolation and characterization. Upon activation, they proliferate and form ductular structures, termed "ductular reactions", which radiate into the hepatic parenchyma. The ductular reactions contain activated progenitor cells that not only acquire a phenotype resembling that observed in developing liver but also display markers of differentiation shared with the cholangiocytic or hepatocytic lineages, the two parenchymal hepatic cell types. Interactions between the putative progenitor cells, the surrounding support cells and the extracellular matrix scaffold, all constituting the progenitor cell niche, are likely to be important for regulating progenitor cell activity and differentiation. Therefore, identifying novel progenitor cell markers and deciphering their microenvironment could facilitate clinical use. The aims of the present PhD thesis were to expand knowledge of the hepatic progenitor cell niche and characterize it both during development and in disease. Several animal models of hepatic injury are known to induce activation of the progenitor cells. In order to identify possible progenitor cell markers and niche components

  7. SUPERNOVA 2008bk AND ITS RED SUPERGIANT PROGENITOR

    SciTech Connect

    Van Dyk, Schuyler D.; Elias-Rosa, Nancy; and others

    2012-01-15

    We have obtained limited photometric and spectroscopic data for supernova (SN) 2008bk in NGC 7793, primarily at {approx}> 150 days after explosion. We find that it is a Type II-Plateau (II-P) SN that most closely resembles the low-luminosity SN 1999br in NGC 4900. Given the overall similarity between the observed light curves and colors of SNe 2008bk and 1999br, we infer that the total visual extinction to SN 2008bk (A{sub V} = 0.065 mag) must be almost entirely due to the Galactic foreground, similar to what has been assumed for SN 1999br. We confirm the identification of the putative red supergiant (RSG) progenitor star of the SN in high-quality g'r'i' images we had obtained in 2007 at the Gemini-South 8 m telescope. Little ambiguity exists in this progenitor identification, qualifying it as the best example to date, next to the identification of the star Sk -69 Degree-Sign 202 as the progenitor of SN 1987A. From a combination of photometry of the Gemini images with that of archival, pre-SN, Very Large Telescope JHK{sub s} images, we derive an accurate observed spectral energy distribution (SED) for the progenitor. We find from nebular strong-intensity emission-line indices for several H II regions near the SN that the metallicity in the environment is likely subsolar (Z Almost-Equal-To 0.6 Z{sub Sun }). The observed SED of the star agrees quite well with synthetic SEDs obtained from model RSG atmospheres with effective temperature T{sub eff} = 3600 {+-} 50 K. We find, therefore, that the star had a bolometric luminosity with respect to the Sun of log (L{sub bol}/L{sub Sun} ) = 4.57 {+-} 0.06 and radius R{sub *} = 496 {+-} 34 R{sub Sun} at {approx}6 months prior to explosion. Comparing the progenitor's properties with theoretical massive-star evolutionary models, we conclude that the RSG progenitor had an initial mass in the range of 8-8.5 M{sub Sun }. This mass is consistent with, albeit at the low end of, the inferred range of initial masses for SN II

  8. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    PubMed

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. PMID:24920757

  9. Simultaneous characterization of progenitor cell compartments in adult human liver.

    PubMed

    Porretti, Laura; Cattaneo, Alessandra; Colombo, Federico; Lopa, Raffaella; Rossi, Giorgio; Mazzaferro, Vincenzo; Battiston, Carlo; Svegliati-Baroni, Gianluca; Bertolini, Francesco; Rebulla, Paolo; Prati, Daniele

    2010-01-01

    The human liver is a complex tissue consisting of epithelial, endothelial, hematopoietic, and mesenchymal elements that probably derive from multiple lineage-committed progenitors, but no comprehensive study aimed at identifying and characterizing intrahepatic precursors has yet been published. Cell suspensions for this study were obtained by enzymatic digestion of liver specimens taken from 20 patients with chronic liver disease and 13 multiorgan donors. Stem and progenitor cells were first isolated, amplified, and characterized ex vivo according to previously validated methods, and then optimized flow cytometry was used to assess their relative frequencies and characterize their immunophenotypes in the clinical specimens. Stem and progenitor cells committed to hematopoietic, endothelial, epithelial, and mesenchymal lineages were clearly identifiable in livers from both healthy and diseased subjects. Within the mononuclear liver cell compartment, epithelial progenitors [epithelial cell adhesion molecule (EpCAM)(+)/CD49f(+)/CD29(+)/CD45(-)] accounted for 2.7-3.5% whereas hematopoietic (CD34(+)/CD45(+)), endothelial [vascular endothelial growth factor-2 (KDR)(+)/CD146(+)/CD45(-)], and mesenchymal [CD73(+)/CD105(+)/CD90 (Thy-1)(+)/CD45 (-)] stem cells and progenitors accounted for smaller fractions (0.02-0.6%). The patients' livers had higher percentages of hematopoietic and endothelial precursors than those of the donors. In conclusion, we identified and characterized precursors committed to four different lineages in adult human liver. We also optimized a flow cytometry approach that will be useful in exploring the contribution of these cells to the pathogenesis of liver disease. PMID:19960544

  10. The Progenitor Mass of the Magnetar SGR1900+14

    NASA Astrophysics Data System (ADS)

    Davies, Ben; Figer, Don F.; Kudritzki, Rolf-Peter; Trombley, Christine; Kouveliotou, Chryssa; Wachter, Stefanie

    2009-12-01

    Magnetars are young neutron stars with extreme magnetic fields (B gsim 1014-1015 G). How these fields relate to the properties of their progenitor stars is not yet clearly established. However, from the few objects associated with young clusters it has been possible to estimate the initial masses of the progenitors, with results indicating that a very massive progenitor star (M prog> 40 M _{⊙}) is required to produce a magnetar. Here, we present adaptive-optics assisted Keck/NIRC2 imaging and Keck/NIRSPEC spectroscopy of the cluster associated with the magnetar SGR 1900+14, and report that the initial progenitor star mass of the magnetar was a factor of 2 lower than this limit, M prog = 17 ± 2 M_{⊙}. Our result presents a strong challenge to the concept that magnetars can only result from very massive progenitors. Instead, we favor a mechanism which is dependent on more than just initial stellar mass for the production of these extreme magnetic fields, such as the "fossil-field" model or a process involving close binary evolution.

  11. Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation

    SciTech Connect

    Colleselli, Daniela; Bijuklic, Klaudija; Mosheimer, Birgit A.; Kaehler, Christian M. . E-mail: C.M.Kaehler@uibk.ac.at

    2006-09-10

    Growing evidence indicates that inducible cyclooxygenase-2 (COX-2) is involved in the pathogenesis of inflammatory disorders and various types of cancer. Endothelial progenitor cells recruited from the bone marrow have been shown to be involved in the formation of new vessels in malignancies and discussed for being a key point in tumour progression and metastasis. However, until now, nothing is known about an interaction between COX and endothelial progenitor cells (EPC). Expression of COX-1 and COX-2 was detected by semiquantitative RT-PCR and Western blot. Proliferation kinetics, cell cycle distribution and rate of apoptosis were analysed by MTT test and FACS analysis. Further analyses revealed an implication of Akt phosphorylation and caspase-3 activation. Both COX-1 and COX-2 expression can be found in bone-marrow-derived endothelial progenitor cells in vitro. COX-2 inhibition leads to a significant reduction in proliferation of endothelial progenitor cells by an increase in apoptosis and cell cycle arrest. COX-2 inhibition leads further to an increased cleavage of caspase-3 protein and inversely to inhibition of Akt activation. Highly proliferating endothelial progenitor cells can be targeted by selective COX-2 inhibition in vitro. These results indicate that upcoming therapy strategies in cancer patients targeting COX-2 may be effective in inhibiting tumour vasculogenesis as well as angiogenic processes.

  12. Impaired DNA replication within progenitor cell pools promotes leukemogenesis.

    PubMed

    Bilousova, Ganna; Marusyk, Andriy; Porter, Christopher C; Cardiff, Robert D; DeGregori, James

    2005-12-01

    Impaired cell cycle progression can be paradoxically associated with increased rates of malignancies. Using retroviral transduction of bone marrow progenitors followed by transplantation into mice, we demonstrate that inhibition of hematopoietic progenitor cell proliferation impairs competition, promoting the expansion of progenitors that acquire oncogenic mutations which restore cell cycle progression. Conditions that impair DNA replication dramatically enhance the proliferative advantage provided by the expression of Bcr-Abl or mutant p53, which provide no apparent competitive advantage under conditions of healthy replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in contexts of impaired DNA replication dramatically increases leukemogenesis. Impaired replication within hematopoietic progenitor cell pools can select for oncogenic events and thereby promote leukemia, demonstrating the importance of replicative competence in the prevention of tumorigenesis. The demonstration that replication-impaired, poorly competitive progenitor cell pools can promote tumorigenesis provides a new rationale for links between tumorigenesis and common human conditions of impaired DNA replication such as dietary folate deficiency, chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important for DNA metabolism. PMID:16277552

  13. Renal blood flow and oxygenation drive nephron progenitor differentiation

    PubMed Central

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K.; Bates, Carlton M.

    2014-01-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. PMID:24920757

  14. Derivation of endodermal progenitors from pluripotent stem cells†

    PubMed Central

    Ikonomou, Laertis; Kotton, Darrell N.

    2014-01-01

    Stem and progenitor cells play important roles in organogenesis during development and in tissue homeostasis and response to injury postnatally. As the regenerative capacity of many human tissues is limited, cell replacement therapies hold great promise for human disease management. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are prime candidates for the derivation of unlimited quantities of clinically relevant cell types through development of directed differentiation protocols, i.e. the recapitulation of developmental milestones in in vitro cell culture. Tissue-specific progenitors, including progenitors of endodermal origin, are important intermediates in such protocols since they give rise to all mature parenchymal cells. In this review, we focus on the in vivo biology of embryonic endodermal progenitors in terms of key transcription factors and signaling pathways. We critically review the emerging literature aiming to apply this basic knowledge to achieve the efficient and reproducible in vitro derivation of endodermal progenitors such as pancreas, liver and lung precursor cells. PMID:25160562

  15. Observational Clues to the Progenitors of Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Maoz, Dan; Mannucci, Filippo; Nelemans, Gijs

    2014-08-01

    Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites—pre- and postexplosion—from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress.

  16. Ex vivo expansion of human peripheral blood progenitors.

    PubMed

    Chabannon, C; Herrera-Rodriguez, D; Bardin, F; Mouren, M; Novakovitch, G; Blaise, D; Maraninchi, D; Mannoni, P

    1995-01-01

    Culture of human hematopoietic progenitors on a large scale could lead to several clinical applications within the near future, including the production of differentiated and functional cells, the increase in the number of early progenitors, especially stem cells, with such use as gene transfer, or the improvement of grafts used to limit the hematological toxicity associated with high-dose chemotherapy. In this case, one can still distinguish different objectives: improvement of grafts that contain low numbers of progenitors because of prior chemotherapies or because of marrow involvement for example, and qualitative changes in the graft content that would allow to envision the disappearance, or the further reduction, in the duration of absolute neutropenia that follows delivery of high dose chemotherapy ("nadir rescue"), despite substitution of mobilized blood cells to marrow cells and the in vivo use of hematopoietic growth factors. Additional advantages may be related to tumor purging in autologous expanded cells, and to the change in the ratio between hematopoietic progenitors and immunocompetent cells in allogeneic expanded populations. Therefore it appears that in vitro expansion currently raises two types of questions: the first ones are related to the definition of clinical or biological endpoints to be achieved, the second ones are related to "bioengineering", and deal with the efficiency and safety of progenitor cell cultures to be used for clinical applications. We here present preliminary results preparing future pilot clinical studies with ex vivo cultured human hematopoietic cells. PMID:8907631

  17. Rates and progenitors of type Ia supernovae

    SciTech Connect

    Wood-Vasey, William Michael

    2004-08-16

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z {approx} 0.01-0.1 of r{sub V} = 4.26{sub -1.93 -0.10}{sup +1.39 +0.10} h{sup 3} x 10{sup -4} SNe Ia/yr/Mpc{sup 3} from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  18. Rates and progenitors of type Ia supernovae

    NASA Astrophysics Data System (ADS)

    Wood-Vasey, William Michael

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of r V = [Special characters omitted.] h 3 x 10 -4 SNe Ia/yr/Mpc 3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  19. Thermonuclear supernova light curves: Progenitors and cosmology

    NASA Astrophysics Data System (ADS)

    Rodney, Steven A.

    Thermonuclear Supernovae (TN SNe) are an extremely important tool in modern astronomy. In their role as cosmological distance probes, they have revealed the accelerated expansion of the universe and have begun to constrain the nature of the dark energy that may be driving that expansion. The next decade will see a succession of wide-field surveys producing thousands of TNSN detections each year. Traditional methods of SN analysis, rooted in time-intensive spectroscopic follow-up, will become completely impractical. To realize the potential of this coming tide of massive data sets, we will need to extract cosmographic parameters (redshift and luminosity distance) from SN photometry without any spectroscopic support. In this dissertation, I present the Supernova Ontology with Fuzzy Templates (SOFT) method, an innovative new approach to the analysis of SN light curves. SOFT uses the framework of fuzzy set theory to perform direct comparisons of SN candidates against template light curves, simultaneously producing both classifications and cosmological parameter estimates. The SOFT method allows us to shed new light on two rich archival data sets. I revisit the IfA Deep Survey and HST GOODS to extract new and improved measurements of the TNSN rate from z=0.2 out to z=1.6. Our new analysis shows a steady increase in the TNSN rate out to z˜1, and adds support for a decrease in the rate at z=1.5. Comparing these rate measurements to theoretical models, I conclude that the progenitor scenario most favored by the collective observational data is a single degenerate model, regulated by a strong wind from the accreting white dwarf. Using a compilation of SN light curves from five recent surveys, I demonstrate that SOFT is able to derive useful constraints on cosmological models from a data set with no spectroscopic information at all. Looking ahead to the near future, I find that photometric analysis of data sets containing 2,000 SNe will be able to improve our constraints on

  20. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    PubMed Central

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  1. Models for supernova progenitors in massive binary systems

    NASA Astrophysics Data System (ADS)

    Yoon, Sung Chul

    2014-09-01

    The diversity of core-collapse supernovae is closely related to binary interactions. For example, the majority of Type Ib/c and Type IIb supernovae may occur in massive binary systems as a result of mass transfer at various evolutionary stages. I will present some evolutionary models of massive binary stars including several important physical ingredients, like tidal interactions and mass and angular momentum exchange, and discuss their implications for supernova progenitors and their populations. I will particularly emphasize that Type Ib/c supernova progenitors at their pre-supernova stage should have very different properties compared to the observed Wolf-Rayet stars, which are widely believed to represent SN Ibc progenitors, and that many observed properties of SNe Ib/c and IIb can be explained well with the binary scenario.

  2. Osteocytes serve as a progenitor cell of osteosarcoma

    PubMed Central

    Sottnik, Joseph L; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L.; Keller, Evan T.

    2016-01-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, an SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. PMID:24700678

  3. Osteocytes serve as a progenitor cell of osteosarcoma.

    PubMed

    Sottnik, Joseph L; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L; Keller, Evan T

    2014-08-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, a SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. PMID:24700678

  4. Endothelial progenitor cells and burn injury - exploring the relationship.

    PubMed

    Banyard, Derek A; Adnani, Blake O; Melkumyan, Satenik; Araniego, Cheryl Ann; Widgerow, Alan D

    2016-01-01

    Burn wounds result in varying degrees of soft tissue damage that are typically graded clinically. Recently a key participant in neovascularization, the endothelial progenitor cell, has been the subject of intense cardiovascular research to explore whether it can serve as a biomarker for vascular injury. In this review, we examine the identity of the endothelial progenitor cell as well as the evidence that support its role as a key responder after burn insult. While there is conflicting evidence with regards to the delta of endothelial progenitor cell mobilization and burn severity, it is clear that they play an important role in wound healing. Systematic and controlled studies are needed to clarify this relationship, and whether this population can serve as a biomarker for burn severity. PMID:27574674

  5. Myogenic Progenitors from Mouse Pluripotent Stem Cells for Muscle Regeneration.

    PubMed

    Magli, Alessandro; Incitti, Tania; Perlingeiro, Rita C R

    2016-01-01

    Muscle homeostasis is maintained by resident stem cells which, in both pathologic and non-pathologic conditions, are able to repair or generate new muscle fibers. Although muscle stem cells have tremendous regenerative potential, their application in cell therapy protocols is prevented by several restrictions, including the limited ability to grow ex vivo. Since pluripotent stem cells have the unique potential to both self-renew and expand almost indefinitely, they have become an attractive source of progenitors for regenerative medicine studies. Our lab has demonstrated that embryonic stem cell (ES)-derived myogenic progenitors retain the ability to repair existing muscle fibers and contribute to the pool of resident stem cells. Because of their relevance in both cell therapy and disease modeling, in this chapter we describe the protocol to derive myogenic progenitors from murine ES cells followed by their intramuscular delivery in a murine muscular dystrophy model. PMID:27492174

  6. Glial Progenitors as Targets for Transformation in Glioma

    PubMed Central

    Ilkanizadeh, Shirin; Lau, Jasmine; Huang, Miller; Foster, Daniel J.; Wong, Robyn; Frantz, Aaron; Wang, Susan; Weiss, William A.; Persson, Anders I.

    2014-01-01

    Glioma is the most common primary malignant brain tumor and arises throughout the central nervous system (CNS). Recent focus on stem-like glioma cells has implicated neural stem cells (NSCs), a minor precursor population restricted to germinal zones, as a potential source of gliomas. In this review, we will focus on the relationship between oligodendrocyte progenitor cells (OPCs), the largest population of cycling glial progenitors in the postnatal brain, and gliomas. Recent studies suggest that OPCs can give rise to gliomas. Furthermore, signaling pathways often associated with NSCs also play key roles during OPC lineage development. Recent advances suggesting that gliomas can undergo a switch from progenitor- to stem-like phenotype after therapy, implicating that an OPC-origin is more likely than previously recognized. Future in-depth studies of OPC biology may shed light on the etiology of OPC-derived gliomas and reveal new therapeutic avenues. PMID:24889528

  7. Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells

    PubMed Central

    Maki, Takakuni; Shindo, Akihiro; Osumi, Noriko; Zhao, Jing; Lin, Hong; Holder, Julie C.; Chuang, Tsu Tshen; McNeish, John D.; Arai, Ken; Lo, Eng H.

    2015-01-01

    Adult mammalian brain can be plastic after injury and disease. Therefore, boosting endogenous repair mechanisms would be a useful therapeutic approach for neurological disorders. Isoxazole-9 (Isx-9) has been reported to enhance neurogenesis from neural stem/progenitor cells (NSPCs). However, the effects of Isx-9 on other types of progenitor/precursor cells remain mostly unknown. In this study, we investigated the effects of Isx-9 on the three major populations of progenitor/precursor cells in brain: NSPCs, oligodendrocyte precursor cells (OPCs), and endothelial progenitor cells (EPCs). Cultured primary NSPCs, OPCs, or EPCs were treated with various concentrations of Isx-9 (6.25, 12.5, 25, 50 μM), and their cell numbers were counted in a blinded manner. Isx-9 slightly increased the number of NSPCs and effectively induced neuronal differentiation of NSPCs. However, Isx-9 significantly decreased OPC number in a concentration-dependent manner, suggesting cytotoxicity. Isx-9 did not affect EPC cell number. But in a matrigel assay of angiogenesis, Isx-9 significantly inhibited tube formation in outgrowth endothelial cells derived from EPCs. This potential anti-tube-formation effect of Isx-9 was confirmed in a brain endothelial cell line. Taken together, our data suggest that mechanisms and targets for promoting stem/progenitor cells in the central nervous system may significantly differ between cell types. PMID:26407349

  8. Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage.

    PubMed

    Woolthuis, Carolien M; Park, Christopher Y

    2016-03-10

    The classical model of hematopoiesis has long held that hematopoietic stem cells (HSCs) sit at the apex of a developmental hierarchy in which HSCs undergo long-term self-renewal while giving rise to cells of all the blood lineages. In this model, self-renewing HSCs progressively lose the capacity for self-renewal as they transit into short-term self-renewing and multipotent progenitor states, with the first major lineage commitment occurring in multipotent progenitors, thus giving rise to progenitors that initiate the myeloid and lymphoid branches of hematopoiesis. Subsequently, within the myeloid lineage, bipotent megakaryocyte-erythrocyte and granulocyte-macrophage progenitors give rise to unipotent progenitors that ultimately give rise to all mature progeny. However, over the past several years, this developmental scheme has been challenged, with the origin of megakaryocyte precursors being one of the most debated subjects. Recent studies have suggested that megakaryocytes can be generated from multiple pathways and that some differentiation pathways do not require transit through a requisite multipotent or bipotent megakaryocyte-erythrocyte progenitor stage. Indeed, some investigators have argued that HSCs contain a subset of cells with biased megakaryocyte potential, with megakaryocytes directly arising from HSCs under steady-state and stress conditions. In this review, we discuss the evidence supporting these nonclassical megakaryocytic differentiation pathways and consider their relative strengths and weaknesses as well as the technical limitations and potential pitfalls in interpreting these studies. Ultimately, such pitfalls will need to be overcome to provide a comprehensive and definitive understanding of megakaryopoiesis. PMID:26787736

  9. Changes in Chondrogenic Progenitor Populations Associated with Aging and Osteoarthritis

    PubMed Central

    Brady, Kyla; Dickinson, Sally C.

    2015-01-01

    Chondrogenic progenitor populations, including mesenchymal stem cells, represent promising cell-based transplantation or tissue engineering therapies for the regeneration of damaged cartilage. Osteoarthritis (OA) predominantly affects the elderly and is a leading cause of disability worldwide. Advancing age is a prominent risk factor that is closely associated with the onset and progression of the disease. Understanding the influence that aging and OA have on chondrogenic progenitor cells is important to determine how these processes affect the cellular mechanisms of the cells and their capacity to differentiate into functional chondrocytes for use in therapeutic applications. Here, we review the effect of age- and OA-related changes on the growth kinetics and differentiation potential of chondrogenic progenitor cell populations. Aging differentially influences the proliferative potential of progenitor cells showing reduced growth rates with increased senescence and apoptotic activity over time, while chondrogenesis appears to be independent of donor age. Cartilage tissue affected by OA shows evidence of progenitor populations with some potential for repair, however reports on the proliferative propensity of mesenchymal stem cells and their chondrogenic potential are contradictory. This is likely attributed to the narrow age ranges of samples assessed and deficits in definitively identifying donors with OA versus healthy patients across a wide scope of advancing ages. Further studies that investigate the mechanistic effects of chondrogenic progenitor populations associated with aging and the progression of OA using clearly defined criteria and age-matched control subject groups are crucial to our understanding of the clinical relevance of these cells for use in cartilage repair therapies. PMID:27340514

  10. Possible Progenitor of Special Supernova Type Detected

    NASA Astrophysics Data System (ADS)

    2008-04-01

    caused by material being pulled off a companion star onto the white dwarf, fusion of this material on the surface of the star should heat the star and produce a strong source of X-radiation prior to the explosion. Once the supernova explosion occurs, the white dwarf is expected to be completely destroyed and then would be undetectable in X-rays. In the merger scenario, the intensity of X-ray emission prior to the explosion is expected to be much weaker. Based on the detection of a fairly strong X-ray source at approximately the position of SN 2007on 4 years before the explosion, Voss and Nelemans conclude that the data support the scenario where matter is pulled off a companion star. The small number of X-ray sources in the field implies that there is only a small chance of an unrelated source being so close by coincidence. Also, the X-ray source has similar properties to those expected for fusion on a white dwarf, unlike most X-ray sources in the sky. However, in follow-up studies, Voss, Nelemans and colleagues Gijs Roelofs (Harvard-Smithsonian Center for Astrophysics, Cambridge, Mass.) and Cees Bassa (McGill University, Canada) used higher-quality optical images to better determine the supernova's position. This work, which is not yet published, shows a small, but significant difference in the measured positions of the supernova and the X-ray source, suggesting the source may not be the progenitor. Follow-up Chandra observations hint that the X-ray object has disappeared, but further observations are needed to finally decide whether the source was the progenitor or not. The team is also applying this new method to other supernovas and has high hopes that they will eventually succeed in identifying the elusive cause of at least some of these explosions. "We're very excited about opening up a new way of studying supernovas, even though we're not sure that we've seen this particular stellar bomb before it exploded," said Gijs Roelofs. "We're very confident that we

  11. Endothelial progenitors in sepsis: vox clamantis in deserto?

    PubMed

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the regenerative capacity of mobilized EPCs and the dissociation between the numerical value and clonogenic competence. Attempting to restore the competence to EPCs should be a priority in the future. PMID:21489327

  12. ON IDENTIFYING THE PROGENITORS OF Type Ia SUPERNOVAE

    SciTech Connect

    Livio, Mario; Pringle, J. E.

    2011-10-10

    We propose two new means of identifying the main class of progenitors of Type Ia supernovae-single or double degenerate: (1) if the range of supernova properties is significantly determined by the range of viewing angles of non-spherically symmetric explosions, then the nature of the correlation between polarization and another property (for example, the velocity gradient) can be used to determine the geometry of the asymmetry and hence the nature of the progenitor, and (2) in the double- but not in the single-degenerate case, the range in the observed properties (e.g., velocity gradients) is likely to increase with the amount of carbon seen in the ejecta.

  13. Subventricular zone progenitors in time and space: generating neuronal diversity

    PubMed Central

    Sequerra, Eduardo B.

    2014-01-01

    The adult mammalian brain harbors a population of cells around their lateral ventricles capable of giving rise to new neurons throughout life. The so-called subventricular zone (SVZ) is a heterogeneous germinative niche in regard to the neuronal types it generates. SVZ progenitors give rise to different olfactory bulb (OB) interneuron types in accordance to their position along the ventricles. Here, I review data showing the difference between progenitors located along different parts of the SVZ axes and ages. I also discuss possible mechanisms for the origin of this diversity. PMID:25565967

  14. Enrichment and terminal differentiation of striated muscle progenitors in vitro

    SciTech Connect

    Becher, Ulrich M.; Breitbach, Martin; Sasse, Philipp; Garbe, Stephan; Ven, Peter F.M. van der; Fuerst, Dieter O.; Fleischmann, Bernd K.

    2009-10-01

    Enrichment and terminal differentiation of mammalian striated muscle cells is severely hampered by fibroblast overgrowth, de-differentiation and/or lack of functional differentiation. Herein we report a new, reproducible and simple method to enrich and terminally differentiate muscle stem cells and progenitors from mice and humans. We show that a single gamma irradiation of muscle cells induces their massive differentiation into structurally and functionally intact myotubes and cardiomyocytes and that these cells can be kept in culture for many weeks. Similar results are also obtained when treating skeletal muscle-derived stem cells and progenitors with Mitomycin C.

  15. Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow

    PubMed Central

    Lee, Jaeyop; Breton, Gaëlle; Oliveira, Thiago Yukio Kikuchi; Zhou, Yu Jerry; Aljoufi, Arafat; Puhr, Sarah; Cameron, Mark J.; Sékaly, Rafick-Pierre

    2015-01-01

    In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common dendritic progenitors (CDPs), demonstrate increasing commitment to the DC lineage, as they sequentially lose granulocyte and monocyte potential, respectively. Identifying these progenitors has enabled us to understand the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34+ hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, and NK and B cells. Using this culture system, we defined the pathway for human DC development and revealed the sequential origin of human DCs from increasingly restricted progenitors: a human granulocyte-monocyte-DC progenitor (hGMDP) that develops into a human monocyte-dendritic progenitor (hMDP), which in turn develops into monocytes, and a human CDP (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte-macrophage progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues. PMID:25687283

  16. Type Ia supernovae: explosions and progenitors

    NASA Astrophysics Data System (ADS)

    Kerzendorf, Wolfgang Eitel

    2011-08-01

    that they somehow need to acquire mass if they are to explode as SN Ia. Currently there are two major scenarios for this mass acquisition. In the favoured single degenerate scenario the white dwarf accretes matter from a companion star which is much younger in its evolutionary state. The less favoured double degenerate scenario sees the merger of two white dwarfs (with a total combined mass of more than 1.38 Msun). This thesis has tried to answer the question about the mass acquisition in two ways. First the single degenerate scenario predicts a surviving companion post-explosion. We undertook an observational campaign to find this companion in two ancient supernovae (SN 1572 and SN 1006). Secondly, we have extended an existing code to extract the elemental and energy yields of SNe Ia spectra by automating spectra fitting to specific SNe Ia. This type of analysis, in turn, help diagnose to which of the two major progenitor scenarios is right.

  17. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors.

    PubMed

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Manuel; Grapin-Botton, Anne

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages of development (2-4). These culture methods have been useful to test drugs and to image developmental processes. However the expansion of the organ is very limited and morphogenesis is not faithfully recapitulated since the organ flattens. We propose three-dimensional (3D) culture conditions that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess the response to mechanical cues of the niche such as stiffness and the effects on cell´s tensegrity. PMID:25079453

  18. Stem cells and progenitor cells in renal disease.

    PubMed

    Haller, Hermann; de Groot, Kirsten; Bahlmann, Ferdinand; Elger, Marlies; Fliser, Danilo

    2005-11-01

    Stem cells and progenitor cells are necessary for repair and regeneration of injured renal tissue. Infiltrating or resident stem cells can contribute to the replacement of lost or damaged tissue. However, the regulation of circulating progenitor cells is not well understood. We have analyzed the effects of erythropoietin on circulating progenitor cells and found that low levels of erythropoietin induce mobilization and differentiation of endothelial progenitor cells. In an animal model of 5/6 nephrectomy we could demonstrate that erythropoietin ameliorates tissue injury. Full regeneration of renal tissue demands the existence of stem cells and an adequate local "milieu," a so-called stem cell niche. We have previously described a stem cell niche in the kidneys of the dogfish, Squalus acanthus. Further analysis revealed that in the regenerating zone of the shark kidney, stem cells exist that can be induced by loss of renal tissue to form new glomeruli. Such animal models improve our understanding of stem cell behavior in the kidney and may eventually contribute to novel therapies. PMID:16221168

  19. Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors

    PubMed Central

    Jönsson, Marie E.; Björklund, Anders; Parish, Clare L.; Thompson, Lachlan H.

    2015-01-01

    An important challenge for the continued development of cell therapy for Parkinson’s disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a “FACS-array” approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations. PMID:25775569

  20. Secondary Sphere Formation Enhances the Functionality of Cardiac Progenitor Cells

    PubMed Central

    Cho, Hyun-Jai; Lee, Ho-Jae; Youn, Seock-Won; Koh, Seok-Jin; Won, Joo-Yun; Chung, Yeon-Ju; Cho, Hyun-Ju; Yoon, Chang-Hwan; Lee, Sae-Won; Lee, Eun Ju; Kwon, Yoo-Wook; Lee, Hae-Young; Lee, Sang Hun; Ho, Won-Kyung; Park, Young-Bae; Kim, Hyo-Soo

    2012-01-01

    Loss of cardiomyocytes impairs cardiac function after myocardial infarction (MI). Recent studies suggest that cardiac stem/progenitor cells could repair the damaged heart. However, cardiac progenitor cells are difficult to maintain in terms of purity and multipotency when propagated in two-dimensional culture systems. Here, we investigated a new strategy that enhances potency and enriches progenitor cells. We applied the repeated sphere formation strategy (cardiac explant → primary cardiosphere (CS) formation → sphere-derived cells (SDCs) in adherent culture condition → secondary CS formation by three-dimensional culture). Cells in secondary CS showed higher differentiation potentials than SDCs. When transplanted into the infarcted myocardium, secondary CSs engrafted robustly, improved left ventricular (LV) dysfunction, and reduced infarct sizes more than SDCs did. In addition to the cardiovascular differentiation of transplanted secondary CSs, robust vascular endothelial growth factor (VEGF) synthesis and secretion enhanced neovascularization in the infarcted myocardium. Microarray pathway analysis and blocking experiments using E-selectin knock-out hearts, specific chemicals, and small interfering RNAs (siRNAs) for each pathway revealed that E-selectin was indispensable to sphere initiation and ERK/Sp1/VEGF autoparacrine loop was responsible for sphere maturation. These results provide a simple strategy for enhancing cellular potency for cardiac repair. Furthermore, this strategy may be implemented to other types of stem/progenitor cell-based therapy. PMID:22713697

  1. Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells

    PubMed Central

    Liu, Yang; Jiang, Bi-Jie; Zhao, Run-Zhen; Ji, Hong-Long

    2016-01-01

    Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na+ channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells. Since ENaC activity and expression are development- and differentiation-dependent, apically located ENaC activity has therefore been used as a functional biomarker of lung injury repair. ENaC activity may be involved in the migration and differentiation of local and circulating stem/progenitor cells with diverse functions, eventually benefiting stem cells spreading to re-epithelialize injured lungs. This review summarizes the potential roles of ENaC expressed in native progenitor and stem cells in the development and regeneration of the respiratory epithelium. PMID:27570489

  2. cKit+ cardiac progenitors of neural crest origin

    PubMed Central

    Hatzistergos, Konstantinos E.; Takeuchi, Lauro M.; Saur, Dieter; Seidler, Barbara; Dymecki, Susan M.; Mai, Jia Jia; White, Ian A.; Balkan, Wayne; Kanashiro-Takeuchi, Rosemeire M.; Schally, Andrew V.; Hare, Joshua M.

    2015-01-01

    The degree to which cKit-expressing progenitors generate cardiomyocytes in the heart is controversial. Genetic fate-mapping studies suggest minimal contribution; however, whether or not minimal contribution reflects minimal cardiomyogenic capacity is unclear because the embryonic origin and role in cardiogenesis of these progenitors remain elusive. Using high-resolution genetic fate-mapping approaches with cKitCreERT2/+ and Wnt1::Flpe mouse lines, we show that cKit delineates cardiac neural crest progenitors (CNCkit). CNCkit possess full cardiomyogenic capacity and contribute to all CNC derivatives, including cardiac conduction system cells. Furthermore, by modeling cardiogenesis in cKitCreERT2-induced pluripotent stem cells, we show that, paradoxically, the cardiogenic fate of CNCkit is regulated by bone morphogenetic protein antagonism, a signaling pathway activated transiently during establishment of the cardiac crescent, and extinguished from the heart before CNC invasion. Together, these findings elucidate the origin of cKit+ cardiac progenitors and suggest that a nonpermissive cardiac milieu, rather than minimal cardiomyogenic capacity, controls the degree of CNCkit contribution to myocardium. PMID:26438843

  3. Hmga2 regulates self-renewal of retinal progenitors

    PubMed Central

    Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

    2014-01-01

    In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. PMID:25336737

  4. Direct Differentiation of Adult Ocular Progenitors into Striatal Dopaminergic Neurons

    PubMed Central

    Ahmad, Iqbal; Zhao, Xing; Parameswaran, Sowmya; Destache, Christopher J.; Rodriguez-Sierra, Jorge; Thoreson, Wallace B.; Ahmad, Hiba; Sorrentino, John; Balasubramanian, Sudha

    2015-01-01

    Parkinson’s disease, characterized by motor dysfunction due to the loss of nigrostriatal dopaminergic neurons, is one of the most prevalent age-related neurodegenerative disorders. Given there is no current cure, the stem cell approach has emerged as a viable therapeutic option to replace the dopaminergic neurons that are progressively lost to the disease. The success of the approach is likely to depend upon accessible, renewable, immune compatible, and non-tumorigenic sources of neural progenitors from which stable dopaminergic neurons can be generated efficaciously. Here, we demonstrate that neural progenitors derived from limbus, a regenerative and accessible ocular tissue, represent a safe source of dopaminergic neurons. When the limbus-derived neural progenitors were subjected to a well-established protocol of directed differentiation under the influence of Shh and FGF8, they acquired the biochemical and functional phenotype of dopaminergic neurons that included the ability to synthesize dopamine. Their intrastriatal transplantation in the rat model of hemi-Parkinsonism was associated with a reduction in the amphetamine-induced rotation. No tumor formation was observed 6 weeks post-transplantation. Together, these observations posit limbus-derived neural progenitors as an accessible and safe source of dopaminergic neurons for a potential autologous ex-vivo stem cell approach to Parkinson’s disease. PMID:26019760

  5. In Vitro Pancreas Organogenesis from Dispersed Mouse Embryonic Progenitors

    PubMed Central

    Grapin-Botton, Anne

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells 1. The whole embryonic organ can be cultured at multiple stages of development 2-4. These culture methods have been useful to test drugs and to image developmental processes. However the expansion of the organ is very limited and morphogenesis is not faithfully recapitulated since the organ flattens. We propose three-dimensional (3D) culture conditions that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess the response to mechanical cues of the niche such as stiffness and the effects on cell´s tensegrity. PMID:25079453

  6. Hepatic cancer stem cells may arise from adult ductal progenitors

    PubMed Central

    Nikolaou, Kostas C; Talianidis, Iannis

    2016-01-01

    Cancer stem cells (CSCs) are defined as cells within tumors that can self-renew and differentiate into heterogeneous lineages of cancerous cells. The origin of CSCs is not well understood. Recent evidence suggests that CSCs in hepatocellular carcinoma could be generated via oncogenic transformation and partial differentiation of adult hepatic ductal progenitor cells.

  7. Direct differentiation of adult ocular progenitors into striatal dopaminergic neurons.

    PubMed

    Ahmad, Iqbal; Zhao, Xing; Parameswaran, Sowmya; Destache, Christopher J; Rodriguez-Sierra, Jorge; Thoreson, Wallace B; Ahmad, Hiba; Sorrentino, John; Balasubramanian, Sudha

    2015-05-01

    Parkinson's disease, characterized by motor dysfunction due to the loss of nigrostriatal dopaminergic neurons, is one of the most prevalent age-related neurodegenerative disorders. Given there is no current cure, the stem cell approach has emerged as a viable therapeutic option to replace the dopaminergic neurons that are progressively lost to the disease. The success of the approach is likely to depend upon accessible, renewable, immune compatible, and non-tumorigenic sources of neural progenitors from which stable dopaminergic neurons can be generated efficaciously. Here, we demonstrate that neural progenitors derived from limbus, a regenerative and accessible ocular tissue, represent a safe source of dopaminergic neurons. When the limbus-derived neural progenitors were subjected to a well-established protocol of directed differentiation under the influence of Shh and FGF8, they acquired the biochemical and functional phenotype of dopaminergic neurons that included the ability to synthesize dopamine. Their intrastriatal transplantation in the rat model of hemi-Parkinsonism was associated with a reduction in the amphetamine-induced rotation. No tumor formation was observed 6 weeks post-transplantation. Together, these observations posit limbus-derived neural progenitors as an accessible and safe source of dopaminergic neurons for a potential autologous ex-vivo stem cell approach to Parkinson's disease. PMID:26019760

  8. LPS induces pulp progenitor cell recruitment via complement activation.

    PubMed

    Chmilewsky, F; Jeanneau, C; Laurent, P; About, I

    2015-01-01

    Complement system, a major component of the natural immunity, has been recently identified as an important mediator of the dentin-pulp regeneration process through STRO-1 pulp cell recruitment by the C5a active fragment. Moreover, it has been shown recently that under stimulation with lipoteichoic acid, a complex component of the Gram-positive bacteria cell wall, human pulp fibroblasts are able to synthesize all proteins required for complement activation. However, Gram-negative bacteria, which are also involved in tooth decay, are known as powerful activators of complement system and inflammation. Here, we investigated the role of Gram-negative bacteria-induced complement activation on the pulp progenitor cell recruitment using lipopolysaccharide (LPS), a major component of all Gram-negative bacteria. Our results show that incubating pulp fibroblasts with LPS induced membrane attack complex formation and C5a release in serum-free fibroblast cultures. The produced C5a binds to the pulp progenitor cells' membrane and induces their migration toward the LPS stimulation chamber, as revealed by the dynamic transwell migration assays. The inhibition of this migration by the C5aR-specific antagonist W54011 indicates that the pulp progenitor migration is mediated by the interaction between C5a and C5aR. Our findings demonstrate, for the first time, a direct interaction between the recruitment of progenitor pulp cells and the activation of complement system generated by pulp fibroblast stimulation with LPS. PMID:25359783

  9. Endometrial stem/progenitor cells: the first 10 years

    PubMed Central

    Gargett, Caroline E.; Schwab, Kjiana E.; Deane, James A.

    2016-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstrual blood stem cells' until December 2014. RESULTS Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44+ cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146+PDGFRβ+ (platelet-derived growth factor receptor beta) and SUSD2+ (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2+ cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman

  10. UPDATE ON THE CETUS POLAR STREAM AND ITS PROGENITOR

    SciTech Connect

    Yam, William; Carlin, Jeffrey L.; Newberg, Heidi Jo; Dumas, Julie; O'Malley, Erin; Newby, Matthew; Martin, Charles

    2013-10-20

    We trace the Cetus Polar Stream (CPS) with blue horizontal branch and red giant stars from Data Release 8 of the Sloan Digital Sky Survey. Using a larger data set than was available previously, we are able to refine the measured distance and velocity to this tidal debris star stream in the south Galactic cap. Assuming that the tidal debris traces the progenitor's orbit, we fit an orbit to the CPS and find that the stream is confined between ∼24 and 36 kpc on a rather polar orbit inclined 87° to the Galactic plane. The eccentricity of the orbit is 0.20, and the period is ∼700 Myr. If we instead matched N-body simulations to the observed tidal debris, these orbital parameters would change by 10% or less. The CPS stars travel in the opposite direction to those from the Sagittarius tidal stream in the same region of the sky. Through N-body models of satellites on the best-fitting orbit, and assuming that mass follows light, we show that the stream width, line-of-sight depth, and velocity dispersion imply a progenitor of ∼> 10{sup 8} M{sub ☉}. However, the density of stars along the stream requires either a disruption time on the order of one orbit or a stellar population that is more centrally concentrated than the dark matter. We suggest that an ultrafaint dwarf galaxy progenitor could reproduce a large stream width and velocity dispersion without requiring a very recent deflection of the progenitor into its current orbit. We find that most Cetus stars have metallicities of –2.5 < [Fe/H] <–2.0, similar to the observed metallicities of the ultrafaint dwarfs. Our simulations suggest that the parameters of the dwarf galaxy progenitors, including their dark matter content, could be constrained by observations of their tidal tails through comparison of the debris with N-body simulations.

  11. Alteration of cardiac progenitor cell potency in GRMD dogs.

    PubMed

    Cassano, M; Berardi, E; Crippa, S; Toelen, J; Barthelemy, I; Micheletti, R; Chuah, M; Vandendriessche, T; Debyser, Z; Blot, S; Sampaolesi, M

    2012-01-01

    Among the animal models of Duchenne muscular dystrophy (DMD), the Golden Retriever muscular dystrophy (GRMD) dog is considered the best model in terms of size and pathological onset of the disease. As in human patients presenting with DMD or Becker muscular dystrophies (BMD), the GRMD is related to a spontaneous X-linked mutation of dystrophin and is characterized by myocardial lesions. In this respect, GRMD is a useful model to explore cardiac pathogenesis and for the development of therapeutic protocols. To investigate whether cardiac progenitor cells (CPCs) isolated from healthy and GRMD dogs may differentiate into myocardial cell types and to test the feasibility of cell therapy for cardiomyopathies in a preclinical model of DMD, CPCs were isolated from cardiac biopsies of healthy and GRMD dogs. Gene profile analysis revealed an active cardiac transcription network in both healthy and GRMD CPCs. However, GRMD CPCs showed impaired self-renewal and cardiac differentiation. Population doubling and telomerase analyses highlighted earlier senescence and proliferation impairment in progenitors isolated from GRMD cardiac biopsies. Immunofluorescence analysis revealed that only wt CPCs showed efficient although not terminal cardiac differentiation, consistent with the upregulation of cardiac-specific proteins and microRNAs. Thus, the pathological condition adversely influences the cardiomyogenic differentiation potential of cardiac progenitors. Using PiggyBac transposon technology we marked CPCs for nuclear dsRed expression, providing a stable nonviral gene marking method for in vivo tracing of CPCs. Xenotransplantation experiments in neonatal immunodeficient mice revealed a valuable contribution of CPCs to cardiomyogenesis with homing differences between wt and dystrophic progenitors. These results suggest that cardiac degeneration in dystrophinopathies may account for the progressive exhaustion of local cardiac progenitors and shed light on cardiac stemness in

  12. Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties

    PubMed Central

    2014-01-01

    Introduction Multipotent progenitor populations exist within the tendon proper and peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials. Methods Isolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types. Results The cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in peritenon

  13. MiR-128-2 inhibits common lymphoid progenitors from developing into progenitor B cells

    PubMed Central

    Chen, Huo; Fei, Xia; Tang, YuXu; Yan, Yunqiu; Zhang, Huimin; Zhang, Jinping

    2016-01-01

    A considerable number of studies revealed that B cell development is finely regulated by transcription factors (TFs). Recent studies suggested that TFs are coordinated with microRNAs to control the development of B cells in numerous checkpoints. In the present study, we first found that miR-128-2 was differentially expressed in various immune organs and immunocytes. B cell development was inhibited in miR-128-2-overexpressed chimera and transgenic (TG) mice in bone marrow with decreased preproB, preB, proB, immature B, and recirculating B cells, as well as increased common lymphoid progenitors (CLPs). Further experiments showed that the apoptosis of CLP decreased, but proliferation was not altered in miR-128-2-overexpressed mice. Extensive studies suggested that the inhibition of apoptosis of CLP may be caused by miR-128-2 targeting A2B and MALT1, thereby increasing the phosphorylation of ERK and P38 MAPK. Such findings have prompted future investigations on the function of miR-128-2 in lymph genesis. PMID:27008703

  14. Stem cell biology is population biology: differentiation of hematopoietic multipotent progenitors to common lymphoid and myeloid progenitors

    PubMed Central

    2013-01-01

    The hematopoietic stem cell (HSC) system is a demand control system, with the demand coming from the organism, since the products of the common myeloid and lymphoid progenitor (CMP, CLP respectively) cells are essential for activity and defense against disease. We show how ideas from population biology (combining population dynamics and evolutionary considerations) can illuminate the feedback control of the HSC system by the fully differentiated products, which has recently been verified experimentally. We develop models for the penultimate differentiation of HSC Multipotent Progenitors (MPPs) into CLP and CMP and introduce two concepts from population biology into stem cell biology. The first concept is the Multipotent Progenitor Commitment Response (MPCR) which is the probability that a multipotent progenitor cell follows a CLP route rather than a CMP route. The second concept is the link between the MPCR and a measure of Darwinian fitness associated with organismal performance and the levels of differentiated lymphoid and myeloid cells. We show that many MPCRs are consistent with homeostasis, but that they will lead to different dynamics of cells and signals following a wound or injury and thus have different consequences for Darwinian fitness. We show how coupling considerations of life history to dynamics of the HSC system and its products allows one to compute the selective pressures on cellular processes. We discuss ways that this framework can be used and extended. PMID:23327512

  15. Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors

    PubMed Central

    Edri, Reuven; Yaffe, Yakey; Ziller, Michael J.; Mutukula, Naresh; Volkman, Rotem; David, Eyal; Jacob-Hirsch, Jasmine; Malcov, Hagar; Levy, Carmit; Rechavi, Gideon; Gat-Viks, Irit; Meissner, Alexander; Elkabetz, Yechiel

    2015-01-01

    Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin of diverse progenitors, for defining their lineages, and for identifying fate determinants driving transition through distinct potencies. Here we have prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state. We first isolate early neuroepithelial cells and show their broad Notch-dependent developmental and proliferative potential. Neuroepithelial cells further yield successive Notch-dependent functional primary progenitors, from early and midneurogenic radial glia and their derived basal progenitors, to gliogenic radial glia and adult-like neural progenitors, together recapitulating hallmarks of neural stem cell (NSC) ontogeny. Gene expression profiling reveals dynamic stage-specific transcriptional patterns that may link development of distinct progenitor identities through Notch activation. Our observations provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modelling development in health and disease. PMID:25799239

  16. Mesenchymal cells. Defining a mesenchymal progenitor niche at single-cell resolution.

    PubMed

    Kumar, Maya E; Bogard, Patrick E; Espinoza, F Hernán; Menke, Douglas B; Kingsley, David M; Krasnow, Mark A

    2014-11-14

    Most vertebrate organs are composed of epithelium surrounded by support and stromal tissues formed from mesenchyme cells, which are not generally thought to form organized progenitor pools. Here, we use clonal cell labeling with multicolor reporters to characterize individual mesenchymal progenitors in the developing mouse lung. We observe a diversity of mesenchymal progenitor populations with different locations, movements, and lineage boundaries. Airway smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding airways. Progenitors recruited from these tip pools differentiate into ASM around airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a lateral bud or by an airway tip plus focal Wnt signal. Thus, mesenchymal progenitors can be organized into localized and carefully controlled domains that rival epithelial progenitor niches in regulatory sophistication. PMID:25395543

  17. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    PubMed Central

    Chabab, Samira; Lescroart, Fabienne; Rulands, Steffen; Mathiah, Navrita; Simons, Benjamin D.; Blanpain, Cédric

    2015-01-01

    Summary The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues. PMID:26725109

  18. Search for Type Ia supernova progenitors in open star clusters

    NASA Astrophysics Data System (ADS)

    Chakraborty, Subho

    2013-12-01

    Though Type Ia supernovae (henceforth SNae) are a primary tool in refining our understanding of cosmology and dark energy, controversies still abound regarding what the progenitors of these SNae are. The two main classes of possible Type Ia SN progenitors are: (1) the single-degenerate model, where a white dwarf (the remnant of a Sun-like star that has completed its life cycle) gravitationally accretes material from a close companion star, and (2) the double-degenerate model, involving the merger of two white dwarfs. In either case, the resulting SN explosion looks the same superficially. But some of the details of the SNae, perhaps including details critical to understanding dark energy, may depend sensitively on what the progenitors are. The goal of this thesis was to search for radial velocity variations in two candidate double degenerate systems. Firstly, I determined if either of these systems were bona fide double degenerates. I used the well-tested method of searching for radial velocity variations due to orbital motion as determined by changing Doppler shifts in their optical spectra. These data were obtained from time-series spectra of both candidate systems over several hours at the world's largest ground based optical telescope, the Keck Observatory in Hawaii. Secondly, I tested whether each confirmed binary system is of sufficient mass and sufficiently short orbital period to be progenitors of a future Type Ia SN. Binary white dwarfs that will merge to form Type IaSNae over a Hubble time have orbital periods less than six hours, which are easily detectable with these data. Type Ia SN progenitors must also have a mass near or above the Chandrasekhar limit of ~1.44 solar masses; the total mass of these systems can also be determined from our data. If one or both of these candidate systems had met both these criteria, the white dwarfs would have been the first definitive examples of the double degenerate class of Type Ia progenitors. This result, which we

  19. Adrenocortical Stem and Progenitor Cells—Implications for Adrenocortical Carcinoma

    PubMed Central

    Simon, Derek P.; Hammer, Gary D.

    2012-01-01

    The continuous centripetal repopulation of the adrenal cortex is consistent with a population of cells endowed with the stem/progenitor cell properties of self-renewal and pluripotency. The adrenocortical capsule and underlying undifferentiated cortical cells are emerging as critical components of the stem/progenitor cell niche. Recent genetic analysis has identified various signaling pathways including Sonic Hedgehog (Shh) and Wnt as crucial mediators of adrenocortical lineage and organ homeostasis. Shh expression is restricted to the peripheral cortical cells that express a paucity of steroidogenic genes but give rise to the underlying differentiated cells of the cortex. Wnt/β-catenin signaling maintains the undifferentiated state and adrenal fate of adrenocortical stem/progenitor cells, in part through induction of its target genes Dax1 and inhibin-α, respectively. The pathogenesis of ACC, a rare yet highly aggressive cancer with an extremely poor prognosis, is slowly emerging from studies of the stem/progenitor cells of the adrenal cortex coupled with the genetics of familial syndromes in which ACC occurs. The frequent observation of constitutive activation of Wnt signaling due to loss-of-function mutations in the tumor suppressor gene APC or gain-of-function mutation in β-catenin in both adenomas and carcinomas, suggests perhaps that the Wnt pathway serves an early or initiating insult in the oncogenic process. Loss of p53 might be predicted to cooperate with additional genetic insults such as IGF2 as both are the most common genetic abnormalities in malignant versus benign adrenocortical neoplasms. It is unclear whether other factors such as Pod1 and Pref1, which are implicated in stem/progenitor cell biology in the adrenal and/or other organs, are also implicated in the etiology of adrenocortical carcinoma. The rarity and heterogeneous presentation of ACC makes it difficult to identify the cellular origin and the molecular progression to cancer. A more

  20. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    PubMed Central

    Consalvi, Silvia; Sandoná, Martina

    2016-01-01

    In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD). PMID:26839565

  1. THE POPULATION OF HELIUM-MERGER PROGENITORS: OBSERVATIONAL PREDICTIONS

    SciTech Connect

    Fryer, Chris L.; Belczynski, Krzysztof; Bulik, Tomasz; Berger, Edo; Thoene, Christina

    2013-02-20

    The helium-merger gamma-ray burst (GRB) progenitor is produced by the rapid accretion onto a compact remnant (neutron star or black hole) when it undergoes a common envelope inspiral with its companion's helium core. This merger phase produces a very distinct environment around these outbursts and recent observations suggest that, in some cases, we are detecting the signatures of the past merger in the GRB afterglow. These observations allow us, for the first time, to study the specific features of the helium-merger progenitor. In this paper, we couple population synthesis calculations to our current understanding of GRB engines and common envelope evolution to make observational predictions for the helium-merger GRB population. Many mergers do not produce GRB outbursts and we discuss the implications of these mergers with the broader population of astrophysical transients.

  2. Probing the Cirucmstellar Medium of Supernova Progenitors with Swift XRT

    NASA Astrophysics Data System (ADS)

    Russell, Brock; Murillo, Destiny

    2016-06-01

    The circumstellar medium surrounding the progenitor stars of core-collapse supernovae can be studied via the X-ray emission by the shock-heated gas following the supernova. By observing this emission over several days, we are able to determine a rough radial gas density profile. We present results of this analysis for 26 core-collapse supernovae observed by the Swift X-Ray Telescope, including supernovae of various subtypes. Overall, we find the CSM density scales with radius as n ~ r -1.6, with some variation between different subtypes. In addition, we provide updated upper limits on X-ray emission from CSM around progenitor systems of Type Ia supernovae.

  3. Single luminal epithelial progenitors can generate prostate organoids in culture

    PubMed Central

    Chua, Chee Wai; Shibata, Maho; Lei, Ming; Toivanen, Roxanne; Barlow, LaMont J.; Bergren, Sarah K.; Badani, Ketan K.; McKiernan, James M.; Benson, Mitchell C.; Hibshoosh, Hanina; Shen, Michael M.

    2014-01-01

    The intrinsic ability to display self-organizing morphogenetic properties in ex vivo culture may represent a general property of tissue stem cells. Here we show that single luminal stem/progenitor cells can generate prostate organoids in a three-dimensional culture system in the absence of stroma. Organoids generated from CARNs (castration-resistant Nkx3.1-expressing cells) or normal prostate epithelium exhibit tissue architecture containing luminal and basal cells, undergo long-term expansion in culture, and display functional androgen receptor signaling. Lineage-tracing demonstrates that luminal cells are favored for organoid formation, and generate basal cells in culture. Furthermore, tumor organoids can initiate from CARNs after oncogenic transformation, and from mouse models of prostate cancer, and can facilitate analyses of drug response. Finally, we provide evidence supporting the feasibility of organoid studies of human prostate tissue. Our studies underscore the progenitor properties of luminal cells, and identify in vitro approaches for studying prostate biology. PMID:25241035

  4. Endothelial progenitor cells accelerate the resolution of deep vein thrombosis.

    PubMed

    Li, Wen-Dong; Li, Xiao-Qiang

    2016-08-01

    Deep vein thrombosis (DVT) causes high morbidity and mortality. Successful resolution of DVT-related thrombi is the key point in the treatment of DVT. Recently, endothelial progenitor cells (EPCs) which are multipotent progenitor cells mainly residing in human bone marrow have emerged as a promising therapeutic choice for DVT-related thrombus resolution. In this review, we discussed the mobilization and homing property of EPCs into the sites of thrombosis, mechanisms of EPCs in DVT-related thrombus resolution from the aspects of promoting endothelial regeneration, revascularization, vasoactive and angiogenic factor secretion, proteinase generation, thrombus propagation and recurrence prevention, and vein wall remodeling. In addition, we also provide suggestions on EPCs as a therapeutic choice for thrombus resolution. PMID:26187355

  5. Decoding the stellar fossils of the dusty Milky Way progenitors

    NASA Astrophysics Data System (ADS)

    de Bennassuti, M.; Schneider, R.; Valiante, R.; Salvadori, S.

    2014-12-01

    We investigate the metallicity distribution function (MDF) of the Galactic halo and the relative fraction of Carbon-normal and Carbon-rich stars using the semi-analytical code GAMETE. The code reconstructs the hierarchical merger tree of the Milky Way (MW) and follows the star formation history and the metal evolution in individual progenitors, including for the first time the formation and evolution of dust. We predict scaling relations between the dust, metal and gas masses for MW progenitors and compare them with observational data of galaxies at 0 <= z < 6.3. We find that the relative contribution of C-normal and C-enhanced stars to the MDF and its dependence on [Fe/H] allow to discriminate among different Pop III/II transition criteria as well as between different Initial Mass Functions (IMFs) and supernova (SN) yields for Population III stars.

  6. Progenitors of type Ia supernovae in elliptical galaxies

    SciTech Connect

    Gilfanov, M.; Bogdan, A.

    2011-09-21

    Although there is a nearly universal agreement that type Ia supernovae are associated with the thermonuclear disruption of a CO white dwarf, the exact nature of their progenitors is still unknown. The single degenerate scenario envisages a white dwarf accreting matter from a non-degenerate companion in a binary system. Nuclear energy of the accreted matter is released in the form of electromagnetic radiation or gives rise to numerous classical nova explosions prior to the supernova event. We show that combined X-ray output of supernova progenitors and statistics of classical novae predicted in the single degenerate scenario are inconsistent with X-ray and optical observations of nearby early type galaxies and galaxy bulges. White dwarfs accreting from a donor star in a binary system and detonating at the Chandrasekhar mass limit can account for no more than {approx}5% of type Ia supernovae observed in old stellar populations.

  7. Neuromesodermal progenitors and the making of the spinal cord

    PubMed Central

    Henrique, Domingos; Abranches, Elsa; Verrier, Laure; Storey, Kate G.

    2016-01-01

    Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a result of patterning of the anterior neural plate. However, as the molecular mechanisms that specify NMps in vivo are uncovered, and as protocols for generating these bipotent cells from mouse and human pluripotent stem cells in vitro are established, the emerging data suggest that this view needs to be revised. Here, we review the characteristics, regulation, in vitro derivation and in vivo induction of NMps. We propose that these cells arise within primitive streak-associated epiblast via a mechanism that is separable from that which establishes neural fate in the anterior epiblast. We thus argue for the existence of two distinct routes for making central nervous system progenitors. PMID:26329597

  8. The Mammary Gland Microenvironment Directs Progenitor Cell Fate In Vivo

    PubMed Central

    Bussard, Karen M.; Smith, Gilbert H.

    2011-01-01

    The mammary gland is a unique organ that continually undergoes postnatal developmental changes. In mice, the mammary gland is formed via signals from terminal end buds, which direct ductal growth and elongation. Intriguingly, it is likely that the entire cellular repertoire of the mammary gland is formed from a single antecedent cell. Furthermore, in order to produce progeny of varied lineages (e.g., luminal and myoepithelial cells), signals from the local tissue microenvironment influence mammary stem/progenitor cell fate. Data have shown that cells from the mammary gland microenvironment reprogram adult somatic cells from other organs (testes, nerve) into cells that produce milk and express mammary epithelial cell proteins. Similar results were found for human tumorigenic epithelial carcinoma cells. Presently, it is unclear how the deterministic power of the mammary gland microenvironment controls epithelial cell fate. Regardless, signals generated by the microenvironment have a profound influence on progenitor cell differentiation in vivo. PMID:21647291

  9. Pericardial patch venoplasty heals via attraction of venous progenitor cells.

    PubMed

    Bai, Hualong; Wang, Mo; Foster, Trenton R; Hu, Haidi; He, Hao; Hashimoto, Takuya; Hanisch, Jesse J; Santana, Jeans M; Xing, Ying; Dardik, Alan

    2016-06-01

    Pericardial patches are commonly used during cardiovascular surgery to close blood vessels. In arteries, patches accumulate arterial progenitor cells; we hypothesized that venous patches would accumulate venous progenitor cells, in the absence of arterial pressure. We developed a novel rat inferior vena cava (IVC) venotomy model and repaired it with a pericardial patch. Cells infiltrated the patch to form a thick neointima by day 7; some cells were CD34(+)/VEGFR2(+) and CD31(+)/Eph-B4(+) consistent with development of venous identity in the healing patch. Compared to arterial patches, the venous patches had increased neointimal thickness at day 7 without any pseudoaneurysms. Addition of an arteriovenous fistula (AVF) to increase blood flow on the patch resulted in reduced patch neointimal thickness and proliferation, but neointimal thickness was not reversible with AVF ligation. These results show that rat patch venoplasty is a novel model of aggressive venous neointimal hyperplasia. PMID:27354544

  10. Properties of Adult Lung Stem and Progenitor Cells.

    PubMed

    Bertoncello, Ivan

    2016-12-01

    The last decade has seen significant progress in understanding the organisation of regenerative cells in the adult lung. Cell-lineage tracing and in vitro clonogenic assays have enabled the identification and characterisation of endogenous lung epithelial stem and progenitor cells. Selective lung injury models, and genetically engineered mice have revealed highly conserved gene networks, factors, signalling pathways, and cellular interactions important in maintaining lung homeostasis and regulating lung regeneration and repair following injury. This review describes the current models of lung epithelial stem and progenitor cell organisation in adult mice, and the impediments encountered in translational studies aiming to identify and characterise their human homologs. J. Cell. Physiol. 231: 2582-2589, 2016. © 2016 Wiley Periodicals, Inc. PMID:27062064

  11. Efficacy and Safety of Human Retinal Progenitor Cells

    PubMed Central

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  12. Neural stem and progenitor cells in health and disease

    PubMed Central

    Ladran, Ian; Tran, Ngoc; Topol, Aaron; Brennand, Kristen J.

    2014-01-01

    Neural stem/progenitor cells (NSPCs) have the potential to differentiate into neurons, astrocytes, and/or oligodendrocytes. Because these cells can be expanded in culture, they represent a vast source of neural cells. With the recent discovery that patient fibroblasts can be reprogrammed directly into induced NSPCs, the regulation of NSPC fate and function, in the context of cell-based disease models and patient-specific cell-replacement therapies, warrants review. PMID:24068527

  13. Characterization of reversibly immortalized calvarial mesenchymal progenitor cells

    PubMed Central

    Shenaq, Deana S.; Teven, Chad M.; Seitz, Iris A.; Rastegar, Farbod; Greives, Matthew R.; He, Tong-Chuan; Reid, Russell R.

    2015-01-01

    Background Bone morphogenetic proteins (BMPs) play a sentinel role in osteoblastic differentiation, and their implementation into clinical practice can revolutionize cranial reconstruction. Preliminary data suggest a therapeutic role of adenoviral gene delivery of BMPs in murine calvarial defect healing. Poor transgene expression inherent in direct adenoviral therapy prompted investigation of cell-based strategies. Objective To isolate and immortalize calvarial cells as a potential progenitor source for osseous tissue engineering. Materials & Methods Cells were isolated from murine skulls, cultured, and transduced with a retroviral vector bearing the loxP-flanked SV40 large T antigen. Immortalized calvarial cells (iCALs) were evaluated via light microscopy, immunohistochemistry, and flow cytometry to determine whether the immortalization process altered cell morphology or progenitor cell profile. iCALs were then infected with adenoviral vectors encoding BMP-2 or GFP and assessed for early and late stages of osteogenic differentiation. Results Immortalization of calvarial cells did not alter cell morphology as demonstrated by phase contrast microscopy. Mesenchymal progenitor cell markers CD166, CD73, CD44, and CD105 were detected at varying levels in both primary cells and iCALs. Significant elevations in alkaline phosphatase activity, osteocalcin mRNA transcription, and matrix mineralization were detected in BMP-2 treated iCALs compared to GFP treated cells. Gross and histological analyses revealed ectopic bone production from treated cells compared to controls in an in vivo stem cell implantation assay. Conclusion We have established an immortalized osteoprogenitor cell line from juvenile calvarial cells that retain a progenitor cell phenotype and can successfully undergo osteogenic differentiation upon BMP-2 stimulation. These cells provide a valuable platform to investigate the molecular mechanisms underlying intramembranous bone formation and to screen for

  14. The evolution of basal progenitors in the developing non-mammalian brain.

    PubMed

    Nomura, Tadashi; Ohtaka-Maruyama, Chiaki; Yamashita, Wataru; Wakamatsu, Yoshio; Murakami, Yasunori; Calegari, Federico; Suzuki, Kunihiro; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    The amplification of distinct neural stem/progenitor cell subtypes during embryogenesis is essential for the intricate brain structures present in various vertebrate species. For example, in both mammals and birds, proliferative neuronal progenitors transiently appear on the basal side of the ventricular zone of the telencephalon (basal progenitors), where they contribute to the enlargement of the neocortex and its homologous structures. In placental mammals, this proliferative cell population can be subdivided into several groups that include Tbr2(+) intermediate progenitors and basal radial glial cells (bRGs). Here, we report that basal progenitors in the developing avian pallium show unique morphological and molecular characteristics that resemble the characteristics of bRGs, a progenitor population that is abundant in gyrencephalic mammalian neocortex. Manipulation of LGN (Leu-Gly-Asn repeat-enriched protein) and Cdk4/cyclin D1, both essential regulators of neural progenitor dynamics, revealed that basal progenitors and Tbr2(+) cells are distinct cell lineages in the developing avian telencephalon. Furthermore, we identified a small population of subapical mitotic cells in the developing brains of a wide variety of amniotes and amphibians. Our results suggest that unique progenitor subtypes are amplified in mammalian and avian lineages by modifying common mechanisms of neural stem/progenitor regulation during amniote brain evolution. PMID:26732839

  15. The evolution of basal progenitors in the developing non-mammalian brain

    PubMed Central

    Nomura, Tadashi; Ohtaka-Maruyama, Chiaki; Yamashita, Wataru; Wakamatsu, Yoshio; Murakami, Yasunori; Calegari, Federico; Suzuki, Kunihiro; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    The amplification of distinct neural stem/progenitor cell subtypes during embryogenesis is essential for the intricate brain structures present in various vertebrate species. For example, in both mammals and birds, proliferative neuronal progenitors transiently appear on the basal side of the ventricular zone of the telencephalon (basal progenitors), where they contribute to the enlargement of the neocortex and its homologous structures. In placental mammals, this proliferative cell population can be subdivided into several groups that include Tbr2+ intermediate progenitors and basal radial glial cells (bRGs). Here, we report that basal progenitors in the developing avian pallium show unique morphological and molecular characteristics that resemble the characteristics of bRGs, a progenitor population that is abundant in gyrencephalic mammalian neocortex. Manipulation of LGN (Leu-Gly-Asn repeat-enriched protein) and Cdk4/cyclin D1, both essential regulators of neural progenitor dynamics, revealed that basal progenitors and Tbr2+ cells are distinct cell lineages in the developing avian telencephalon. Furthermore, we identified a small population of subapical mitotic cells in the developing brains of a wide variety of amniotes and amphibians. Our results suggest that unique progenitor subtypes are amplified in mammalian and avian lineages by modifying common mechanisms of neural stem/progenitor regulation during amniote brain evolution. PMID:26732839

  16. Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.

    PubMed

    Delaspre, Fabien; Beer, Rebecca L; Rovira, Meritxell; Huang, Wei; Wang, Guangliang; Gee, Stephen; Vitery, Maria del Carmen; Wheelan, Sarah J; Parsons, Michael J

    2015-10-01

    Diabetes is associated with a paucity of insulin-producing β-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in β-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch-responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors. To test our hypothesis that adult CACs are also progenitors, we took two complementary approaches: 1) We established the transcriptome for adult CACs. Using gene ontology, transgenic lines, and in situ hybridization, we found that the CAC transcriptome is enriched for progenitor markers. 2) Using lineage tracing, we demonstrated that CACs do form new endocrine cells after β-cell ablation or partial pancreatectomy. We concluded that CACs and their larval predecessors are the same cell type and represent an opportune model to study both β-cell neogenesis and β-cell regeneration. Furthermore, we show that in cftr loss-of-function mutants, there is a deficiency of larval CACs, providing a possible explanation for pancreatic complications associated with cystic fibrosis. PMID:26153247

  17. Probing massive stars around gamma-ray burst progenitors

    NASA Astrophysics Data System (ADS)

    Lu, Wenbin; Kumar, Pawan; Smoot, George F.

    2015-10-01

    Long gamma-ray bursts (GRBs) are produced by ultra-relativistic jets launched from core collapse of massive stars. Most massive stars form in binaries and/or in star clusters, which means that there may be a significant external photon field (EPF) around the GRB progenitor. We calculate the inverse-Compton scattering of EPF by the hot electrons in the GRB jet. Three possible cases of EPF are considered: the progenitor is (I) in a massive binary system, (II) surrounded by a Wolf-Rayet-star wind and (III) in a dense star cluster. Typical luminosities of 1046-1050 erg s-1 in the 1-100 GeV band are expected, depending on the stellar luminosity, binary separation (I), wind mass-loss rate (II), stellar number density (III), etc. We calculate the light curve and spectrum in each case, taking fully into account the equal-arrival time surfaces and possible pair-production absorption with the prompt γ-rays. Observations can put constraints on the existence of such EPFs (and hence on the nature of GRB progenitors) and on the radius where the jet internal dissipation process accelerates electrons.

  18. Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

    PubMed Central

    Cairo, Valentina; D'Ascola, Angela; Scuruchi, Michele; Basile, Giorgio; Mandraffino, Giuseppe

    2016-01-01

    Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717. PMID:26839569

  19. Single versus binary star progenitors of Type IIb supernovae

    NASA Astrophysics Data System (ADS)

    Sravan, Niharika

    2016-07-01

    Stripped-envelope supernovae (SNe) represent a challenge to our understanding of massive star evolution. Wind mass loss and binary interactions are the leading candidates to explain observations. The latter has gained support in the recent years with growing evidence that mass-loss rates due to line-driven winds are, in reality, 2 - 3 times lower. Type IIb SNe retain a small amount of their Hydrogen envelope before undergoing core-collapse and are the only class of stripped-envelope SNe with identified progenitors. Thus they are powerful tools for testing our understanding of massive stellar evolution. To identify possible evolutionary pathways to Type IIb SNe, we use Modules for Experiments in Stellar Astrophysics (MESA) to model a large population of single and binary star sequences covering a broad parameter space with a wide range of component masses and initial orbital periods and identify those that undergo core-collapse with 0.01 to 0.5 solar masses of residual Hydrogen envelope. We find no single star Type IIb progenitors in the parameter space covered. We find a few Type IIb binary progenitors. These sequences have initial mass ratios greater than 0.6, wide orbital periods and undergo non-conservative mass transfer.

  20. Where do the progenitors of millisecond pulsars come from?

    NASA Astrophysics Data System (ADS)

    Taani, A.; Zhang, C. M.; Al-Wardat, M.; Zhao, Y. H.

    2012-01-01

    Observations of a large population of millisecond pulsars (MSPs) show a wide divergence in the orbital periods (from approximately hours to a few months). In the standard view, low-mass X-ray binaries (LMXBs) are considered as progenitors for some MSPs during the recycling process. We present a systematic study that combines different types of compact objects in binaries such as cataclysmic variables (CVs), LMXBs, and MSPs. We plot them together in the so called Corbet diagram. Larger and different samples are needed to better constrain the result as a function of the environment and formations. A scale diagram showing the distribution of MSPs for different orbital periods and the aspects for their progenitors relying on accretion induced collapse (AIC) of white dwarfs in binaries. Thus massive CVs (M ≥ 1.1 M⊙) can play a vital role on binary evolution, as well as of the physical processes involved in the formation and evolution of neutron stars and their magnetic fields, and could turn into binary MSPs with different scales of orbital periods; this effect can be explained by the AIC process. This scenario also suggests that some fraction of isolated MSPs in the Galactic disk could be formed through the same channel, forming the contribution of some CVs to the single-degenerate progenitors of Type Ia supernova. Furthermore, we have refined the statistical distribution and evolution by using updated data. This implies that the significant studies of compact objects in binary systems can benefit from the Corbet diagram.

  1. Sox2 in the differentiation of cochlear progenitor cells

    PubMed Central

    Kempfle, Judith S.; Turban, Jack L.; Edge, Albert S. B.

    2016-01-01

    HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair cell differentiation, through an interaction with the 3′ enhancer of Atoh1. Binding to consensus sequences in the Atoh1 enhancer was dependent on the level of Sox2, and the extent of enhancer binding correlated to the extent of activation. Atoh1 activation by Sox2 was required for embryonic hair cell development: deletion of Sox2 in an inducible mutant, even after progenitor cells were fully established, halted development of hair cells, and silencing also inhibited postnatal differentiation of hair cells induced by inhibition of γ-secretase. Sox2 is thus required in the cochlea to both expand the progenitor cells and initiate their differentiation to hair cells. PMID:26988140

  2. Dentin regeneration using deciduous pulp stem/progenitor cells.

    PubMed

    Zheng, Y; Wang, X Y; Wang, Y M; Liu, X Y; Zhang, C M; Hou, B X; Wang, S L

    2012-07-01

    Reparative dentin formation is essential for maintaining the integrity of dentin structure during disease or trauma. In this study, we investigated stem/progenitor cell-based tissue engineering for dentin regeneration in a large animal model. Porcine deciduous pulp stem/progenitor cells (PDPSCs) were mixed with a beta-tricalcium phosphate (β-TCP) scaffold for dentin regeneration. Different concentrations of PDPSCs were tested to determine the optimal density for dentin regeneration. Aliquots of 5×10(5) PDPSCs in 1 mL resulted in the highest number of cells attached to the scaffold and the greatest alkaline phosphatase activity. We labeled PDPSCs with green fluorescent protein (GFP) and used the optimal cell numbers mixed with β-TCP to repair pulp chamber roof defects in the premolars of swine. Four weeks after transplantation, GFP-positive PDPSCs were observed in PDPSC-embedded scaffold constructs. At 16 weeks after transplantation, the PDPSCs mixed with β-TCP significantly regenerated the dentin-like structures and nearly completely restored the pulp chamber roof defects. This study demonstrated that the PDPSC/scaffold construct was useful in direct pulp-capping and provides pre-clinical evidence for stem/progenitor cell-based dentin regeneration. PMID:22660968

  3. Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow.

    PubMed

    Montali, Marina; Barachini, Serena; Pacini, Simone; Panvini, Francesca M; Petrini, Mario

    2016-01-01

    In a research study aimed to isolate human bone marrow (hBM)-derived Mesenchymal Stromal Cells (MSCs) for clinical applications, we identified a novel cell population specifically selected for growth in human serum supplemented medium. These cells are characterized by morphological, phenotypic, and molecular features distinct from MSCs and we named them Mesodermal Progenitor Cells (MPCs). MPCs are round, with a thick highly refringent core region; they show strong, trypsin resistant adherence to plastic. Failure to expand MPCs directly revealed that they are slow in cycling. This is as also suggested by Ki-67 negativity. On the other hand, culturing MPCs in standard medium designed for MSC expansion, gave rise to a population of exponentially growing MSC-like cells. Besides showing mesenchymal differentiation capacity MPCs retained angiogenic potential, confirming their multiple lineage progenitor nature. Here we describe an optimized highly reproducible protocol to isolate and characterize hBM-MPCs by flow cytometry (CD73, CD90, CD31, and CD45), nestin expression, and F-actin organization. Protocols for mesengenic and angiogenic differentiation of MPCs are also provided. Here we also suggest a more appropriate nomenclature for these cells, which has been re-named as "Mesangiogenic Progenitor Cells". PMID:27500428

  4. Role of intermediate progenitor cells in cerebral cortex development.

    PubMed

    Pontious, Adria; Kowalczyk, Tom; Englund, Chris; Hevner, Robert F

    2008-01-01

    Intermediate progenitor cells (IPCs) are a type of neurogenic transient amplifying cells in the developing cerebral cortex. IPCs divide symmetrically at basal (abventricular) positions in the neuroepithelium to produce pairs of new neurons or, in amplifying divisions, pairs of new IPCs. In contrast, radial unit progenitors (neuroepithelial cells and radial glia) divide at the apical (ventricular) surface and produce only single neurons or single IPCs by asymmetric division, or self-amplify by symmetric division. Histologically, IPCs are most prominent during the middle and late stages of neurogenesis, when they accumulate in the subventricular zone, a progenitor compartment linked to the genesis of upper neocortical layers (II-IV). Nevertheless, IPCs are present throughout cortical neurogenesis and produce neurons for all layers. In mice, changes in the abundance of IPCs caused by mutations of Pax6, Ngn2, Id4 and other genes are associated with parallel changes in cortical thickness but not surface area. In gyrencephalic brains, IPCs may play broader roles in determining not only laminar thickness, but also cortical surface area and gyral patterns. We propose that regulation of IPC genesis and amplification across developmental stages and regional subdivisions modulates laminar neurogenesis and contributes to the cytoarchitectonic differentiation of cortical areas. PMID:18075251

  5. Identification of human erythroid lineage-committed progenitors.

    PubMed

    Mori, Yasuo; Akashi, Koichi; Weissman, Irving L

    2016-05-01

    Elucidating the developmental pathway leading to erythrocytes and being able to isolate their progenitors is crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Endoglin (CD105) is a key marker for purifying mouse erythroid lineage-committed progenitors (EPs) from bone marrow. Herein, we show that human EPs can also be isolated from adult bone marrow. We identified three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage-CD34(+)CD38(+)IL-3Rα(-)CD45RA(-)) population. Both CD71(-)CD105(-) and CD71(+)CD105(-) MEPs, at least in vitro, retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter sub-population had a differentiation potential skewed toward the E-lineage. Notably, the differentiation output of the CD71(+)CD105(+) subset of cells within the MEP population was completely restricted to the E-lineage with the loss of MegK potential; thus, we termed CD71(+)CD105(-) MEPs and CD71(+)CD105(+) cells as E-biased MEPs (E-MEPs) and EPs, respectively. These previously unclassified populations may facilitate understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage. PMID:27263782

  6. Morphological and functional aspects of progenitors perturbed in cortical malformations

    PubMed Central

    Bizzotto, Sara; Francis, Fiona

    2015-01-01

    In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs), which are renowned for their unique morphological and behavioral characteristics, constituting a key element during the development of the mammalian cerebral cortex. We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons. Important for disease mechanisms, we overview what is currently known about RGC cellular components, cytoskeletal mechanisms, signaling pathways and cell cycle characteristics, focusing on how defects lead to abnormal development and cortical malformation phenotypes. The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type. Combining data from phenotypes in the mouse reveals molecules which potentially act in common pathways. Going beyond this, we discuss future directions that may provide new data in this expanding area. PMID:25729350

  7. Neutronization During Carbon Simmering In Type Ia Supernova Progenitors

    NASA Astrophysics Data System (ADS)

    Martínez-Rodríguez, Héctor; Piro, Anthony L.; Schwab, Josiah; Badenes, Carles

    2016-07-01

    When a Type Ia supernova (SN Ia) progenitor first ignites carbon in its core, it undergoes ˜103–104 years of convective burning prior to the onset of thermonuclear runaway. This carbon simmering phase is important for setting the thermal profile and composition of the white dwarf. Using the MESA stellar evolution code, we follow this convective burning and examine the production of neutron-rich isotopes. The neutron content of the SN fuel has important consequences for the ensuing nucleosynthesis, and in particular, for the production of secondary Fe-peak nuclei like Mn and stable Ni. These elements have been observed in the X-ray spectra of SN remnants like Tycho, Kepler, and 3C 397, and their yields can provide valuable insights into the physics of SNe Ia and the properties of their progenitors. We find that weak reactions during simmering can at most generate a neutron excess of ≈ 3 × 10‑4. This is ≈ 70% lower than that found in previous studies that do not take the full density and temperature profile of the simmering region into account. Our results imply that the progenitor metallicity is the main contributor to the neutron excess in SN Ia fuel for Z ≳ 1/3 Z ⊙. Alternatively, at lower metallicities, this neutron excess provides a floor that should be present in any centrally-ignited SN Ia scenario.

  8. Neutronization During Carbon Simmering In Type Ia Supernova Progenitors

    NASA Astrophysics Data System (ADS)

    Martínez-Rodríguez, Héctor; Piro, Anthony L.; Schwab, Josiah; Badenes, Carles

    2016-07-01

    When a Type Ia supernova (SN Ia) progenitor first ignites carbon in its core, it undergoes ∼103–104 years of convective burning prior to the onset of thermonuclear runaway. This carbon simmering phase is important for setting the thermal profile and composition of the white dwarf. Using the MESA stellar evolution code, we follow this convective burning and examine the production of neutron-rich isotopes. The neutron content of the SN fuel has important consequences for the ensuing nucleosynthesis, and in particular, for the production of secondary Fe-peak nuclei like Mn and stable Ni. These elements have been observed in the X-ray spectra of SN remnants like Tycho, Kepler, and 3C 397, and their yields can provide valuable insights into the physics of SNe Ia and the properties of their progenitors. We find that weak reactions during simmering can at most generate a neutron excess of ≈ 3 × 10‑4. This is ≈ 70% lower than that found in previous studies that do not take the full density and temperature profile of the simmering region into account. Our results imply that the progenitor metallicity is the main contributor to the neutron excess in SN Ia fuel for Z ≳ 1/3 Z ⊙. Alternatively, at lower metallicities, this neutron excess provides a floor that should be present in any centrally-ignited SN Ia scenario.

  9. Minor histocompatibility antigens on canine hemopoietic progenitor cells.

    PubMed

    Weber, Martin; Lange, Claudia; Günther, Wolfgang; Franz, Monika; Kremmer, Elisabeth; Kolb, Hans-Jochem

    2003-06-15

    Adoptive immunotherapy with CTL against minor histocompatibility Ags (mHA) provides a promising way to treat leukemia relapse in allogeneic chimeras. Here we describe the in vitro generation of CTL against mHA in the dog. We tested their inhibitory effect on the growth of hemopoietic progenitor cells stimulated by hemopoietic growth factors in a 4-day suspension culture. CTL were produced by coculture of donor PBMC with bone marrow-derived dendritic cells (DCs). These DCs were characterized by morphology, high expression of MHC class II and CD1a, and the absence of the monocyte-specific marker CD14. Characteristically these cells stimulated allogeneic lymphocytes (MLR) and, after pulsing with a foreign Ag (keyhole limpet hemocyanin), autologous T cells. CTL were generated either ex vivo by coculture with DCs of DLA-identical littermates or in vivo by immunization of the responder with DCs obtained from a DLA-identical littermate. In suspension culture assays the growth of hemopoietic progenitor cells was inhibited in 53% of DLA-identical littermate combinations. In canine families mHA segregated with DLA as restriction elements. One-way reactivity against mHA was found in five littermate combinations. In two cases mHA might be Y chromosome associated, in three cases autosomally inherited alleles were detected. We conclude that CTL can be produced in vitro and in vivo against mHA on canine hemopoietic progenitor cells using bone marrow-derived DCs. PMID:12794111

  10. Sox2 in the differentiation of cochlear progenitor cells.

    PubMed

    Kempfle, Judith S; Turban, Jack L; Edge, Albert S B

    2016-01-01

    HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair cell differentiation, through an interaction with the 3' enhancer of Atoh1. Binding to consensus sequences in the Atoh1 enhancer was dependent on the level of Sox2, and the extent of enhancer binding correlated to the extent of activation. Atoh1 activation by Sox2 was required for embryonic hair cell development: deletion of Sox2 in an inducible mutant, even after progenitor cells were fully established, halted development of hair cells, and silencing also inhibited postnatal differentiation of hair cells induced by inhibition of γ-secretase. Sox2 is thus required in the cochlea to both expand the progenitor cells and initiate their differentiation to hair cells. PMID:26988140

  11. An Mll-dependent Hox program drives hematopoietic progenitor expansion.

    PubMed

    Ernst, Patricia; Mabon, Meghann; Davidson, Alan J; Zon, Leonard I; Korsmeyer, Stanley J

    2004-11-23

    Chromosomal translocations disrupting the Mixed lineage leukemia (Mll) gene result in leukemia, with aberrant expression of some native Mll target genes (reviewed in). The Mll gene encodes a Trithorax-group chromatin regulator that is essential for the development of hematopoietic stem cells (HSCs) during embryogenesis. Like Trithorax, MLL positively regulates clustered homeodomain or Hox genes, yet the role of Hox genes collectively in the development of the mammalian hematopoietic system has been difficult to ascertain because of redundancy among Hox paralogs. Here, we show that in the absence of MLL, early hematopoietic progenitors develop despite reduced expression of HoxA, HoxB, and HoxC genes. However, these progenitors exhibit a marked reduction in their ability to generate hematopoietic colonies, a subsequent process requiring cell division and differentiation. Reactivation of a subset of Hox genes or, remarkably, reexpression of a single Hox gene in Mll-deficient progenitors rescued hematopoietic-colony frequency and growth. In contrast, expression of other MLL target genes such as Pitx2 or expression of anti-apoptotic BCL-2 failed to rescue hematopoietic-colony frequency. Furthermore, our results highlight a shared function of Hox proteins at this point in the development of the hematopoietic system. PMID:15556871

  12. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  13. Human neural progenitor cells in central nervous system lesions.

    PubMed

    Åkesson, Elisabet; Sundström, Erik

    2016-02-01

    Various immature cells can be isolated from human embryonic and fetal central nervous system (CNS) residual tissue and potentially be used in cell therapy for a number of neurological diseases and CNS insults. Transplantation of neural stem and progenitor cells is essential for replacing lost cells, particularly in the CNS with very limited endogenous regenerative capacity. However, while dopamine released from transplanted cells can substitute the lost dopamine neurons in the experimental models of Parkinson's disease, stem and progenitor cells primarily have a neuroprotective effect, probably through the release of trophic factors. Understanding the therapeutic effects of transplanted cells is crucial to determine the design of clinical trials. During the last few years, a number of clinical trials for CNS diseases and insults such as amyotrophic lateral sclerosis (ALS), stroke, and spinal cord trauma using neural progenitor cells have been initiated. Data from these early studies will provide vital information on the safety of transplanting these cells, which still is a major concern. That the beneficial results observed in experimental models also can be repeated in the clinical setting is highly hoped for. PMID:26803559

  14. NOTCH signaling in skeletal progenitors is critical for fracture repair.

    PubMed

    Wang, Cuicui; Inzana, Jason A; Mirando, Anthony J; Ren, Yinshi; Liu, Zhaoyang; Shen, Jie; O'Keefe, Regis J; Awad, Hani A; Hilton, Matthew J

    2016-04-01

    Fracture nonunions develop in 10%-20% of patients with fractures, resulting in prolonged disability. Current data suggest that bone union during fracture repair is achieved via proliferation and differentiation of skeletal progenitors within periosteal and soft tissues surrounding bone, while bone marrow stromal/stem cells (BMSCs) and other skeletal progenitors may also contribute. The NOTCH signaling pathway is a critical maintenance factor for BMSCs during skeletal development, although the precise role for NOTCH and the requisite nature of BMSCs following fracture is unknown. Here, we evaluated whether NOTCH and/or BMSCs are required for fracture repair by performing nonstabilized and stabilized fractures on NOTCH-deficient mice with targeted deletion of RBPjk in skeletal progenitors, maturing osteoblasts, and committed chondrocytes. We determined that removal of NOTCH signaling in BMSCs and subsequent depletion of this population result in fracture nonunion, as the fracture repair process was normal in animals harboring either osteoblast- or chondrocyte-specific deletion of RBPjk. Together, this work provides a genetic model of a fracture nonunion and demonstrates the requirement for NOTCH and BMSCs in fracture repair, irrespective of fracture stability and vascularity. PMID:26950423

  15. NOTCH signaling in skeletal progenitors is critical for fracture repair

    PubMed Central

    Wang, Cuicui; Inzana, Jason A.; Mirando, Anthony J.; Liu, Zhaoyang; Shen, Jie; O’Keefe, Regis J.; Awad, Hani A.; Hilton, Matthew J.

    2016-01-01

    Fracture nonunions develop in 10%–20% of patients with fractures, resulting in prolonged disability. Current data suggest that bone union during fracture repair is achieved via proliferation and differentiation of skeletal progenitors within periosteal and soft tissues surrounding bone, while bone marrow stromal/stem cells (BMSCs) and other skeletal progenitors may also contribute. The NOTCH signaling pathway is a critical maintenance factor for BMSCs during skeletal development, although the precise role for NOTCH and the requisite nature of BMSCs following fracture is unknown. Here, we evaluated whether NOTCH and/or BMSCs are required for fracture repair by performing nonstabilized and stabilized fractures on NOTCH-deficient mice with targeted deletion of RBPjk in skeletal progenitors, maturing osteoblasts, and committed chondrocytes. We determined that removal of NOTCH signaling in BMSCs and subsequent depletion of this population result in fracture nonunion, as the fracture repair process was normal in animals harboring either osteoblast- or chondrocyte-specific deletion of RBPjk. Together, this work provides a genetic model of a fracture nonunion and demonstrates the requirement for NOTCH and BMSCs in fracture repair, irrespective of fracture stability and vascularity. PMID:26950423

  16. Mesenchymal markers on human adipose stem/progenitor cells

    PubMed Central

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    The stromal-vascular fraction (SVF) of adipose tissue is a rich source of multipotent stem cells. We and others have described 3 major populations of stem/progenitor cells in this fraction, all closely associated with small blood vessels: endothelial progenitor cells (EPC, CD45−/CD31+/CD34+), pericytes (CD45−/CD31−/CD146+) and supra-adventitial adipose stromal cells (SA-ASC, CD45−/CD31−/CD146−/CD34+). EPC are luminal, pericytes are adventitial and SA-ASC surround the vessel like a sheath. The multipotency of the pericytes and SA-ASC compartments is strikingly similar to that of CD45−/CD34−/CD73+/CD105+/CD90+ bone marrow-derived mesenchymal stem cells (BM-MSC). Here we determine the extent to which this mesenchymal expression pattern is expressed on the 3 adipose stem/progenitor populations. Eight independent adipose tissue samples were analyzed in a single tube (CD105-FITC/CD73-PE/CD146-PETXR/CD14-PECY5/CD33-PECY5/CD235A-PECY5/CD31-PECY7/CD90-APC/CD34-A700/CD45-APCCY7/DAPI). Adipose EPC were highly proliferative with 14.3±2.8% (mean ± SEM) having >2N DNA. About half (53.1±7.6%) coexpressed CD73 and CD105, and 71.9±7.4% expressed CD90. Pericytes were less proliferative (8.2±3.4% >2N DNA) with a smaller proportion (29.6±6.9% CD73+/CD105+, 60.5±10.2% CD90+) expressing mesenchymal associated markers. However, the CD34+ subset of CD146+ pericytes, were both highly proliferative (15.1±3.6% with >2N DNA) and of uniform mesenchymal phenotype (93.3±3.7% CD73+/CD105+, 97.8±0.7% CD90+), suggesting transit amplifying progenitor cells. SA-ASC were the least proliferative (3.7 ± 0.8%>2N DNA) but were also highly mesenchymal in phenotype (94.4±3.2% CD73+/CD105+, 95.5±1.2% CD90+). These data imply a progenitor/progeny relationship between pericytes and SA-ASC, the most mesenchymal of SVF cells. Despite phenotypic and functional similarities to BM-MSC, SA-ASC are distinguished by CD34 expression. PMID:23184564

  17. Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.

    PubMed

    Álvarez, Zaida; Hyroššová, Petra; Perales, José Carlos; Alcántara, Soledad

    2016-03-01

    This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity. PMID:25452568

  18. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    PubMed

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development. PMID:27178467

  19. Clonal analysis of human dendritic cell progenitor using a stromal cell culture

    PubMed Central

    Lee, Jaeyop; Breton, Gaëlle; Aljoufi, Arafat; Zhou, Yu Jerry; Puhr, Sarah; Nussenzweig, Michel C.; Liu, Kang

    2015-01-01

    Different dendritic cell (DC) subsets co-exist in humans and coordinate the immune response. Having a short life, DCs must be constantly replenished from their progenitors in the bone marrow through hematopoiesis. Identification of a DC-restricted progenitor in mouse has improved our understanding of how DC lineage diverges from myeloid and lymphoid lineages. However, identification of the DC-restricted progenitor in humans has not been possible because a system that simultaneously nurtures differentiation of human DCs, myeloid and lymphoid cells, is lacking. Here we report a cytokine and stromal cell culture that allows evaluation of CD34+ progenitor potential to all three DC subsets as well as other myeloid and lymphoid cells, at a single cell level. Using this system, we show that human granulocyte–macrophage progenitors are heterogeneous and contain restricted progenitors to DCs. PMID:26056939

  20. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    PubMed

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis. PMID:26460946

  1. Circulating Progenitor Cells in Regenerative Technologies: A Realistic Strategy in Bone Regeneration?

    PubMed Central

    Chang, Jessica B.; Lee, Justine C.

    2016-01-01

    Strategies in skeletal regeneration research have been primarily focused on optimization of three components: cellular progenitors, biomaterials, and growth factors. With the increased understanding that circulating progenitor cells exist in peripheral blood, the question arises whether such cell types would allow for adequate osteogenesis and mineralization. In this review, we discuss the current literature on circulating progenitor cells in in vitro and in vivo studies on bone regeneration. PMID:27331195

  2. Tracking of Normal and Malignant Progenitor Cell Cycle Transit in a Defined Niche

    PubMed Central

    Pineda, Gabriel; Lennon, Kathleen M.; Delos Santos, Nathaniel P.; Lambert-Fliszar, Florence; Riso, Gennarina L.; Lazzari, Elisa; Marra, Marco A.; Morris, Sheldon; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Jamieson, Catriona H. M.

    2016-01-01

    While implicated in therapeutic resistance, malignant progenitor cell cycle kinetics have been difficult to quantify in real-time. We developed an efficient lentiviral bicistronic fluorescent, ubiquitination-based cell cycle indicator reporter (Fucci2BL) to image live single progenitors on a defined niche coupled with cell cycle gene expression analysis. We have identified key differences in cell cycle regulatory gene expression and transit times between normal and chronic myeloid leukemia progenitors that may inform cancer stem cell eradication strategies. PMID:27041210

  3. In Vitro Modeling of Brain Progenitor Cell Development under the Effect of Environmental Factors.

    PubMed

    Kuvacheva, N V; Morgun, A V; Komleva, Yu K; Khilazheva, E D; Gorina, Ya V; Lopatina, O L; Arutyunyan, S A; Salmina, A B

    2015-08-01

    We studied in vitro development of brain progenitor cells isolated from healthy 7-9-month-old Wistar rats and rats with experimental Alzheimer's disease kept under standard conditions and in enriched (multistimulus) environment in vivo. Progenitor cells from healthy animals more rapidly formed neurospheres. Considerable changes at the early stages of in vitro development of brain progenitor cells were observed in both groups kept in enriched environment. PMID:26395632

  4. CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells

    PubMed Central

    Vasyutina, Elena; Stebler, Jürg; Brand-Saberi, Beate; Schulz, Stefan; Raz, Erez; Birchmeier, Carmen

    2005-01-01

    Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the routes and at the targets of the migratory cells. Ectopic application of SDF1 in the chick limb attracts muscle progenitor cells. In CXCR4 mutant mice, the number of muscle progenitors that colonize the anlage of the tongue and the dorsal limb was reduced. Changes in the distribution of the muscle progenitor cells were accompanied by increased apoptosis, indicating that CXCR4 signals provide not only attractive cues but also control survival. Gab1 encodes an adaptor protein that transduces signals elicited by tyrosine kinase receptors, for instance the c-Met receptor, and plays a role in the migration of muscle progenitor cells. We found that CXCR4 and Gab1 interact genetically. For instance, muscle progenitors do not reach the anlage of the tongue in CXCR4;Gab1 double mutants; this target is colonized in either of the single mutants. Our analysis reveals a role of SDF1/CXCR4 signaling in the development of migrating muscle progenitors and shows that a threshold number of progenitor cells is required to generate muscle of appropriate size. PMID:16166380

  5. CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells.

    PubMed

    Vasyutina, Elena; Stebler, Jürg; Brand-Saberi, Beate; Schulz, Stefan; Raz, Erez; Birchmeier, Carmen

    2005-09-15

    Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the routes and at the targets of the migratory cells. Ectopic application of SDF1 in the chick limb attracts muscle progenitor cells. In CXCR4 mutant mice, the number of muscle progenitors that colonize the anlage of the tongue and the dorsal limb was reduced. Changes in the distribution of the muscle progenitor cells were accompanied by increased apoptosis, indicating that CXCR4 signals provide not only attractive cues but also control survival. Gab1 encodes an adaptor protein that transduces signals elicited by tyrosine kinase receptors, for instance the c-Met receptor, and plays a role in the migration of muscle progenitor cells. We found that CXCR4 and Gab1 interact genetically. For instance, muscle progenitors do not reach the anlage of the tongue in CXCR4;Gab1 double mutants; this target is colonized in either of the single mutants. Our analysis reveals a role of SDF1/CXCR4 signaling in the development of migrating muscle progenitors and shows that a threshold number of progenitor cells is required to generate muscle of appropriate size. PMID:16166380

  6. The disappearance of the progenitors of supernovae 1993J and 2003gd.

    PubMed

    Maund, Justyn R; Smartt, Stephen J

    2009-04-24

    Using images from the Hubble Space Telescope and the Gemini Telescope, we confirmed the disappearance of the progenitors of two type II supernovae (SNe) and evaluated the presence of other stars associated with them. We found that the progenitor of SN 2003gd, an M-supergiant star, is no longer observed at the SN location and determined its intrinsic brightness using image subtraction techniques. The progenitor of SN 1993J, a K-supergiant star, is also no longer present, but its B-supergiant binary companion is still observed. The disappearance of the progenitors confirms that these two supernovae were produced by red supergiants. PMID:19299586

  7. Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to airway injury.

    PubMed

    Gomperts, Brigitte N; Belperio, John A; Rao, P Nagesh; Randell, Scott H; Fishbein, Michael C; Burdick, Marie D; Strieter, Robert M

    2006-02-01

    Recipient airway epithelial cells are found in human sex-mismatched lung transplants, implying that circulating progenitor epithelial cells contribute to the repair of the airway epithelium. Markers of circulating progenitor epithelial cells and mechanisms for their trafficking remain to be elucidated. We demonstrate that a population of progenitor epithelial cells exists in the bone marrow and the circulation of mice that is positive for the early epithelial marker cytokeratin 5 (CK5) and the chemokine receptor CXCR4. We used a mouse model of sex-mismatched tracheal transplantation and found that CK5+ circulating progenitor epithelial cells contribute to re-epithelialization of the airway and re-establishment of the pseudostratified epithelium. The presence of CXCL12 in tracheal transplants provided a mechanism for CXCR4+ circulating progenitor epithelial cell recruitment to the airway. Depletion of CXCL12 resulted in the epithelium defaulting to squamous metaplasia, which was derived solely from the resident tissue progenitor epithelial cells. Our findings demonstrate that CK5+CXCR4+ cells are markers of circulating progenitor epithelial cells in the bone marrow and circulation and that CXCR4/CXCL12-mediated recruitment of circulating progenitor epithelial cells is necessary for the re-establishment of a normal pseudostratified epithelium after airway injury. These findings support a novel paradigm for the development of squamous metaplasia of the airway epithelium and for developing therapeutic strategies for circulating progenitor epithelial cells in airway diseases. PMID:16424223

  8. Progenitors of supernova Ibc: a single Wolf-Rayet star as the possible progenitor of the SN Ib iPTF13bvn

    NASA Astrophysics Data System (ADS)

    Groh, Jose H.; Georgy, Cyril; Ekström, Sylvia

    2013-10-01

    Core-collapse supernova (SN) explosions mark the end of the tumultuous life of massive stars. Determining the nature of their progenitors is a crucial step towards understanding the properties of SNe. Until recently, no progenitor has been directly detected for SN of type Ibc, which are believed to come from massive stars that lose their hydrogen envelope through stellar winds and from binary systems where the companion has stripped the H envelope from the primary. Here we analyze recently reported observations of iPTF13bvn, which could possibly be the first detection of a SN Ib progenitor based on pre-explosion images. Very interestingly, the recently published Geneva models of single stars can reproduce the observed photometry of the progenitor candidate and its mass-loss rate, confirming a recently proposed scenario. We find that a single WR star with initial mass in the range 31-35 M⊙ fits the observed photometry of the progenitor of iPTF13bvn. The progenitor likely has a luminosity of log (L⋆/L⊙) ~ 5.55, surface temperature ~45 000 K, and mass of ~10.9 M⊙ at the time of explosion. Our non-rotating 32 M⊙ model overestimates the derived radius of the progenitor, although this could likely be reconciled with a fine-tuned model of a more massive (between 40 and 50 M⊙), hotter, and luminous progenitor. Our models indicate a very uncertain ejecta mass of ~8 M⊙, which is higher than the average of the SN Ib ejecta mass that is derived from the lightcurve (2-4 M⊙). This possibly high ejecta mass could produce detectable effects in the iPTF13bvn lightcurve and spectrum. If the candidate is indeed confirmed to be the progenitor, our results suggest that stars with relatively high initial masses (> 30 M⊙) can produce visible SN explosions at their deaths and do not collapse directly to a black hole.

  9. The role of oligodendrocytes and oligodendrocyte progenitors in CNS remyelination.

    PubMed

    Keirstead, H S; Blakemore, W F

    1999-01-01

    Remyelination enables restoration of saltatory conduction and a return of normal function lost during demyelination. Unfortunately, remyelination is often incomplete in the adult human central nervous system (CNS) and this failure of remyelination is one of the main reasons for clinical deficits in demyelinating disease. An understanding of the failure of remyelination in demyelinating diseases such as Multiple Sclerosis depends upon the elucidation of cellular events underlying successful remyelination. Although the potential for remyelination of the adult CNS has been well established, there is still some dispute regarding the origin of the remyelinating cell population. The literature variously reports that remyelinating oligodendrocytes arise from dedifferentiation and/or proliferation of mature oligodendrocytes, or are generated solely from proliferation and differentiation of glial progenitor cells. This review focuses on studies carried out on remyelinating lesions in the adult rat spinal cord produced by injection of antibodies to galactocerebroside plus serum complement that demonstrate: 1) oligodendrocytes which survive within an area of demyelination do not contribute to remyelination, 2) remyelination is carried out by oligodendrocyte progenitor cells, 3) recruitment of oligodendrocyte progenitors to an area of demyelination is a local response, and 4) division of oligodendrocyte progenitors is symmetrical and results in chronic depletion of the oligodendrocyte progenitor population in the normal white matter around an area of remyelination. These results suggest that failure of remyelination may be contributed to by a depletion of oligodendrocyte progenitors especially following repeated episodes of demyelination. Remyelination allows the return of saltatory conduction (Smith et al., 1979) and the functional recovery of demyelination-induced deficits (Jeffery et al., 1997). Findings such as these have encouraged research aimed at enhancing the limited

  10. Hoxa9 Regulates Flt3 in Lymphohematopoietic Progenitors

    PubMed Central

    Gwin, Kimberly; Frank, Elena; Bossou, Ayoko; Medina, Kay L.

    2014-01-01

    Early B cell factor (EBF) is a transcription factor essential for specification and commitment to the B cell fate. In this study, we show downregulation of a developmentally regulated cluster of hoxa genes, notably hoxa9, coincides with induction of EBF at the Pro-B cell stage of B cell differentiation. Analysis of the hematopoietic progenitor compartment in Hoxa9−/− mice revealed significantly reduced frequencies and expression levels of Flt3, a cytokine receptor important for lymphoid priming and the generation of B cell precursors (BCPs). We show that Hoxa9 directly regulates the flt3 gene. Chromatin immunoprecipitation analysis revealed binding of Hoxa9 to the flt3 promoter in a lymphoid progenitor cell line. Knockdown of Hoxa9 significantly reduced Flt3 transcription and expression. Conversely, forced expression of Hoxa9 increased Flt3 transcription and expression in a Pro-B cell line that expressed low levels of Flt3. Hoxa9 inversely correlated with ebf1 in ex vivo-isolated bone marrow progenitors and BCPs, suggesting that EBF might function to silence a Hoxa9 transcriptional program. Restoration of EBF function in an EBF−/− cell line induced B lineage gene expression but did not directly suppress hoxa9 transcription, revealing alternate mechanisms of Hoxa9 regulation in BCPs. These data provide new insight into Hoxa9 function and regulation during lymphoid and B cell development. Furthermore, they suggest that failure to upregulate Flt3 provides a molecular basis for the lymphoid/early B cell deficiencies in Hoxa9−/− mice. PMID:20971928

  11. Detection of human myeloid progenitor cells in a murine background.

    PubMed

    Carow, C E; Harrington, M A; Broxmeyer, H E

    1993-01-01

    Cell-mixing experiments were performed to determine whether human (hu) peripheral blood plasma would select for the growth of hu myeloid progenitor cells in vitro. Mixtures of hu male umbilical cord blood and murine (mu) female bone marrow (100% hu, 100% mu, 1.0% hu or 10% hu and 50% hu) were plated in methylcellulose cultures that contained either hu plasma or fetal bovine serum (FBS). Cultures were supplemented with recombinant (r) hu erythropoietin (Epo) alone or in combination with rhu granulocyte-macrophage colony stimulating factor (GM-CSF), rmuGM-CSF or rhu steel factor (SLF). DNA was extracted from day 14 colonies and clusters, and the polymerase chain reaction (PCR) was used to detect the hu Y-chromosome satellite DNA sequence. Results of these studies revealed that hu plasma used in combination with hu growth factors selected for the growth of hu progenitor cells. Mu cells grew in hu plasma only at high cell-plating concentrations. This selective effect was due to a heat labile factor or factors, since mu cells grew equally well in heat-inactivated hu plasma and FBS. Cells in individual progenitor cell colonies and clusters cultured in hu plasma contained hu Y-chromosome-specific DNA sequences that were detectable after PCR-mediated amplification, thus eliminating the need for time-consuming Southern transfer. This study describes a method whereby hu/immune-deficient mice can be screened rapidly for hu myeloid engraftment. These results also indicate that the hu identity of colonies and clusters cultured in hu plasma must be genetically confirmed, especially when hu cells may represent a low percentage of the total cells plated. PMID:7678088

  12. Decoding the stellar fossils of the dusty Milky Way progenitors

    NASA Astrophysics Data System (ADS)

    de Bennassuti, Matteo; Schneider, Raffaella; Valiante, Rosa; Salvadori, Stefania

    2014-12-01

    We investigate the metallicity distribution function (MDF) in the Galactic halo and the relative fraction of carbon-normal and carbon-rich stars. To this aim, we use an improved version of the semi-analytical code GAlaxy MErger Tree and Evolution (GAMETE), that reconstructs the hierarchical merger tree of the Milky Way (MW), following the star formation history and the metal and dust evolution in individual progenitors. The predicted scaling relations between the dust, metal and gas masses for MW progenitors show a good agreement with observational data of local galaxies and of gamma-ray burst (GRB) host galaxies at 0.1 < z < 6.3. Comparing the simulated and the observed MDF, we find that in order to predict the formation of hyper-iron-poor stars at [Fe/H] < -4, faint supernova (SN) explosions have to dominate the metal yields produced by Population III (Pop III) stars, disfavouring a Pop III initial mass function that extends to stellar masses >140 M⊙, into the Pair-Instability SN progenitor mass range. The relative contribution of C-normal and C-enhanced stars to the MDF and its dependence on [Fe/H] points to a scenario where the Pop III/II transition is driven by dust cooling, and the first low-mass stars form when the dust-to-gas ratio in their parent clouds exceeds a critical value of {\\cal D}_crit = 4.4 × 10^{-9}. Other transition criteria do not predict any C-normal stars below [Fe/H] < -4, at odds with observations.

  13. Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

    PubMed Central

    Wu, June K.; Kitajewski, Christopher; Reiley, Maia; Keung, Connie H.; Monteagudo, Julie; Andrews, John P.; Liou, Peter; Thirumoorthi, Arul; Wong, Alvin

    2015-01-01

    Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs. PMID:25719418

  14. Osteopontin Neutralization Abrogates the Liver Progenitor Cell Response and Fibrogenesis in Mice

    PubMed Central

    Coombes, J; Swiderska-Syn, M; Dollé, L; Reid, D; Eksteen, B; Claridge, L; Briones-Orta, MA; Shetty, S; Oo, YH; Riva, A; Chokshi, S; Papa, S; Mi, Z; Kuo, PC; Williams, R; Canbay, A; Adams, DH; Diehl, AM; van Grunsven, LA; Choi, SS; Syn, WK

    2015-01-01

    Background Chronic liver injury triggers a progenitor-cell repair-response, and liver fibrosis occurs when repair becomes de-regulated. Previously, we reported that reactivation of the Hedgehog (Hh) pathway promotes fibrogenic liver-repair. Osteopontin (OPN) is a Hh-target, and a cytokine that is highly upregulated in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesized that OPN may modulate liver progenitor-cell response, and thereby, modulate fibrotic outcomes. We further evaluated the impact of OPN-neutralization on murine liver fibrosis. Methods Liver progenitors (603B and BMOL) were treated with OPN-neutralizing aptamers in the presence or absence of TGF–β, to determine if (and how) OPN modulates liver progenitor function. Effects of OPN-neutralization (using OPN-aptamers or OPN-neutralizing antibodies) on liver progenitor-cell response and fibrogenesis were assessed in three models of liver fibrosis (carbon tetrachloride, methionine-choline deficient diet, 3, 5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by qRTPCR, Sirius-Red staining, hydroxyproline assay, and semi-quantitative double-immunohistochemistry. Finally, OPN expression and liver progenitor response were corroborated in liver tissues obtained from patients with chronic liver disease. Results OPN is over-expressed by liver progenitors in humans and mice. In cultured progenitors, OPN enhances viability and wound-healing by modulating TGF-β signaling. In vivo, OPN-neutralization attenuates the liver progenitor-cell response, reverses epithelial-mesenchymal-transition in Sox9+ cells, and abrogates liver fibrogenesis. Conclusions OPN upregulation during liver injury is a conserved repair-response, and influences liver progenitor-cell function. OPN-neutralization abrogates the liver progenitor-cell response and fibrogenesis in mouse models of liver fibrosis. PMID:24902765

  15. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts

    PubMed Central

    Liu, Yu; Chen, Li; Diaz, Andrea Diaz; Benham, Ashley; Xu, Xueping; Wijaya, Cori S.; Fa’ak, Faisal; Luo, Weijia; Soibam, Benjamin; Azares, Alon; Yu, Wei; Lyu, Qiongying; Stewart, M. David; Gunaratne, Preethi; Cooney, Austin; McConnell, Bradley K.; Schwartz, Robert J.

    2016-01-01

    Mesp1 directs multipotential cardiovascular cell fates, even though it’s transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1’s transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1Cre/+; Rosa26EYFP/+ ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells. PMID:27538477

  16. Human Neonatal Cardiovascular Progenitors: Unlocking the Secret to Regenerative Ability

    PubMed Central

    Fuentes, Tania I.; Appleby, Nancy; Tsay, Eric; Martinez, J. Julian; Bailey, Leonard; Hasaniya, Nahidh; Kearns-Jonker, Mary

    2013-01-01

    Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity. PMID:24204836

  17. Recurrent novae as progenitors of Type Ia supernovae

    NASA Astrophysics Data System (ADS)

    Kato, Mariko; Hachisu, Izumi

    2012-09-01

    Recurrent novae are binaries harboring a very massive white dwarf (WD), as massive as the Chandrasekhar mass, because of their short recurrence periods of nova outbursts of 10--100 years. Thus, recurrent novae are considered as candidates of progenitors of Type Ia supernovae (SNe~Ia). In fact, the SN~Ia PTF~11kx showed evidence that its progenitor is a symbiotic recurrent nova. The binary parameters of recurrent novae have been well determined, especially for the ones with frequent outbursts, U Sco and RS Oph, which provide useful information on the elementary processes in binary evolution toward SNe~Ia. Therefore we use them as testbeds for binary evolution models. For example, the original double degenerate (DD) scenario cannot reproduce RS Oph type recurrent novae, whereas the new single degenerate (SD) scenario proposed by Hachisu et al. (1999) naturally can. We review main differences between the SD and DD scenarios, especially for their basic processes of binary evolution. We also discuss observational support for each physical process. The original DD scenario is based on the physics in 1980s, whereas the SD scenario on more recent physics including the new opacity, mass-growth efficiency of WDs, and optically thick winds developed in nova outbursts.

  18. Bone marrow–derived progenitor cells in pulmonary fibrosis

    PubMed Central

    Hashimoto, Naozumi; Jin, Hong; Liu, Tianju; Chensue, Stephen W.; Phan, Sem H.

    2004-01-01

    The origin of fibroblasts in pulmonary fibrosis is assumed to be intrapulmonary, but their extrapulmonary origin and especially derivation from bone marrow (BM) progenitor cells has not been ruled out. To examine this possibility directly, adult mice were durably engrafted with BM isolated from transgenic mice expressing enhanced GFP. Induction of pulmonary fibrosis in such chimera mice by endotracheal bleomycin (BLM) injection caused large numbers of GFP+ cells to appear in active fibrotic lesions, while only a few GFP+ cells could be identified in control lungs. Flow-cytometric analysis of lung cells confirmed the BLM-induced increase in GFP+ cells in chimera mice and revealed a significant increase in GFP+ cells that also express type I collagen. GFP+ lung fibroblasts isolated from chimera mice expressed collagen and telomerase reverse transcriptase but not α-smooth muscle actin. Treatment of isolated GFP+ fibroblasts with TGF-β failed to induce myofibroblast differentiation. Cultured lung fibroblasts expressed the chemokine receptors CXCR4 and CCR7 and responded chemotactically to their cognate ligands, stromal cell–derived factor-1α and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells. PMID:14722616

  19. No surviving evolved companions of the progenitor of SN 1006.

    PubMed

    González Hernández, Jonay I; Ruiz-Lapuente, Pilar; Tabernero, Hugo M; Montes, David; Canal, Ramon; Méndez, Javier; Bedin, Luigi R

    2012-09-27

    Type Ia supernovae are thought to occur when a white dwarf made of carbon and oxygen accretes sufficient mass to trigger a thermonuclear explosion. The accretion could be slow, from an unevolved (main-sequence) or evolved (subgiant or giant) star (the single-degenerate channel), or rapid, as the primary star breaks up a smaller orbiting white dwarf (the double-degenerate channel). A companion star will survive the explosion only in the single-degenerate channel. Both channels might contribute to the production of type Ia supernovae, but the relative proportions of their contributions remain a fundamental puzzle in astronomy. Previous searches for remnant companions have revealed one possible case for SN 1572 (refs 8, 9), although that has been questioned. More recently, observations have restricted surviving companions to be small, main-sequence stars, ruling out giant companions but still allowing the single-degenerate channel. Here we report the results of a search for surviving companions of the progenitor of SN 1006 (ref. 14). None of the stars within 4 arc minutes of the apparent site of the explosion is associated with the supernova remnant, and we can firmly exclude all giant and subgiant stars from being companions of the progenitor. In combination with previous results, our findings indicate that fewer than 20 per cent of type Ia supernovae occur through the single-degenerate channel. PMID:23018963

  20. Prospective heterotopic ossification progenitors in adult human skeletal muscle.

    PubMed

    Downey, Jennifer; Lauzier, Dominique; Kloen, Peter; Klarskov, Klaus; Richter, Martin; Hamdy, Reggie; Faucheux, Nathalie; Scimè, Anthony; Balg, Frédéric; Grenier, Guillaume

    2015-02-01

    Skeletal muscle has strong regenerative capabilities. However, failed regeneration can lead to complications where aberrant tissue forms as is the case with heterotopic ossification (HO), in which chondrocytes, osteoblasts and white and brown adipocytes can arise following severe trauma. In humans, the various HO cell types likely originate from multipotent mesenchymal stromal cells (MSCs) in skeletal muscle, which have not been identified in humans until now. In the present study, adherent cells from freshly digested skeletal muscle tissue were expanded in defined culture medium and were FACS-enriched for the CD73(+)CD105(+)CD90(-) population, which displayed robust multilineage potential. Clonal differentiation assays confirmed that all three lineages originated from a single multipotent progenitor. In addition to differentiating into typical HO lineages, human muscle resident MSCs (hmrMSCs) also differentiated into brown adipocytes expressing uncoupling protein 1 (UCP1). Characterizing this novel multipotent hmrMSC population with a brown adipocyte differentiation capacity has enhanced our understanding of the contribution of non-myogenic progenitor cells to regeneration and aberrant tissue formation in human skeletal muscle. PMID:25445454

  1. Endometrial regeneration and endometrial stem/progenitor cells.

    PubMed

    Gargett, Caroline E; Nguyen, Hong P T; Ye, Louie

    2012-12-01

    The functional layer of the human endometrium is a highly regenerative tissue undergoing monthly cycles of growth, differentiation and shedding during a woman's reproductive years. Fluctuating levels of circulating estrogen and progesterone orchestrate this dramatic remodeling of human endometrium. The thin inactive endometrium of postmenopausal women which resembles the permanent basal layer of cycling endometrium retains the capacity to respond to exogenous sex steroid hormones to regenerate into a thick functional endometrium capable of supporting pregnancy. Endometrial regeneration also follows parturition and endometrial resection. In non menstruating rodents, endometrial epithelium undergoes rounds of proliferation and apoptosis during estrus cycles. The recent identification of adult stem cells in both human and mouse endometrium suggests that epithelial progenitor cells and the mesenchymal stem/stromal cells have key roles in the cyclical regeneration of endometrial epithelium and stroma. This review will summarize the evidence for endometrial stem/progenitor cells, examine their role in mouse models of endometrial epithelial repair and estrogen-induced endometrial regeneration, and also describe the generation of endometrial-like epithelium from human embryonic stem cells. With markers now available for identifying endometrial mesenchymal stem/stromal cells, their possible role in gynecological diseases associated with abnormal endometrial proliferation and their potential application in cell-based therapies to regenerate reproductive and other tissues will be discussed. PMID:22847235

  2. Transplantation of Adrenal Cortical Progenitor Cells Enriched by Nile Red

    PubMed Central

    Dunn, James C.Y.; Chu, Yinting; Qin, Harry H.; Zupekan, Tatiana

    2009-01-01

    Background The adrenal cortex may contain progenitor cells useful for tissue regeneration. Currently there are no established methods to isolate these cells. Material and Methods Murine adrenal cells were sorted into a Nile-Red-bright (NRbright) and a Nile-Red-dim (NRdim) population of cells according to their degree of cholesterol content revealed by Nile Red fluorescence. The cells were transplanted under the renal capsule to determine their ability for regeneration. Results The NRbright cells contained an abundance of lipid droplets, whereas the NRdim cells contained little. The NRbright cells expressed Sf1 and the more differentiated adrenal cortical genes including Cyp11a1, Cyp11b1, and Cyp11b2, whereas the NRdim cells expressed Sf1 but not the more differentiated adrenal cortical genes. After 56 days of implantation in unilateral adrenalectomized mice, the NRdim cells expressed Sf1 and the more differentiated adrenal cortical genes, whereas the NRbright cells ceased to express Sf1 as well as the more differentiated adrenal cortical genes. NRdim cells also proliferated in the presence of basic fibroblast growth factor. Conclusions The population of NRdim cells contained adrenal cortical progenitor cells that can proliferate and give rise to differentiated daughter cells. These cells may be useful for adrenal cortical regeneration. PMID:19592014

  3. Thermonuclear Supernova Explosions From Hybrid White Dwarf Progenitors

    NASA Astrophysics Data System (ADS)

    Willcox, Donald E.; Townsley, Dean; Calder, Alan; Denissenkov, Pavel; Herwig, Falk

    2016-01-01

    Motivated by recent results in stellar evolution in which convective boundary mixing in SAGB stars can give rise to hybrid white dwarf (WD) stars with a C-O core inside an O-Ne shell, we simulate thermonuclear (Type Ia) supernovae from these hybrid progenitors. We use the FLASH code to perform multidimensional simulations in the deflagration to detonation transition (DDT) explosion paradigm from progenitor models produced with the MESA stellar evolution code that include the thermal energetics of the Urca process. We performed a suite of DDT simulations over a range of ignition conditions and compare to previous results from a suite of C-O white dwarfs. Despite significant variability within each suite, distinguishing trends are apparent in their Ni-56 yields and the kinetic properties of their ejecta. We comment on the feasibility of these hybrid WD explosions as the source of some classes of observed subluminous events. This research was supported in part by the U.S. Department of Energy under grant DE-FG02-87ER40317 and by resources at the Institute for Advanced Computational Science at Stony Brook University. The software used in this work was in part developed by the DOE-supported ASC/Alliances Center for Astrophysical Thermonuclear Flashes at the University of Chicago.

  4. Microtubules CLASP to Adherens Junctions in epidermal progenitor cells.

    PubMed

    Shahbazi, Marta N; Perez-Moreno, Mirna

    2014-01-01

    Cadherin-mediated cell adhesion at Adherens Junctions (AJs) and its dynamic connections with the microtubule (MT) cytoskeleton are important regulators of cellular architecture. However, the functional relevance of these interactions and the molecular players involved in different cellular contexts and cellular compartments are still not completely understood. Here, we comment on our recent findings showing that the MT plus-end binding protein CLASP2 interacts with the AJ component p120-catenin (p120) specifically in progenitor epidermal cells. Absence of either protein leads to alterations in MT dynamics and AJ functionality. These findings represent a novel mechanism of MT targeting to AJs that may be relevant for the maintenance of proper epidermal progenitor cell homeostasis. We also discuss the potential implication of other MT binding proteins previously associated to AJs in the wider context of epithelial tissues. We hypothesize the existence of adaptation mechanisms that regulate the formation and stability of AJs in different cellular contexts to allow the dynamic behavior of these complexes during tissue homeostasis and remodeling. PMID:24522006

  5. Microtubules CLASP to Adherens Junctions in epidermal progenitor cells

    PubMed Central

    Shahbazi, Marta N; Perez-Moreno, Mirna

    2014-01-01

    Cadherin-mediated cell adhesion at Adherens Junctions (AJs) and its dynamic connections with the microtubule (MT) cytoskeleton are important regulators of cellular architecture. However, the functional relevance of these interactions and the molecular players involved in different cellular contexts and cellular compartments are still not completely understood. Here, we comment on our recent findings showing that the MT plus-end binding protein CLASP2 interacts with the AJ component p120-catenin (p120) specifically in progenitor epidermal cells. Absence of either protein leads to alterations in MT dynamics and AJ functionality. These findings represent a novel mechanism of MT targeting to AJs that may be relevant for the maintenance of proper epidermal progenitor cell homeostasis. We also discuss the potential implication of other MT binding proteins previously associated to AJs in the wider context of epithelial tissues. We hypothesize the existence of adaptation mechanisms that regulate the formation and stability of AJs in different cellular contexts to allow the dynamic behavior of these complexes during tissue homeostasis and remodeling. PMID:24522006

  6. Transcription factor induction of human oligodendrocyte progenitor fate and differentiation.

    PubMed

    Wang, Jing; Pol, Suyog U; Haberman, Alexa K; Wang, Chunming; O'Bara, Melanie A; Sim, Fraser J

    2014-07-15

    Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a(+)O4(+) OPCs relative to CD133(+)CD140a(-) neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs. PMID:24982138

  7. Transcription factor induction of human oligodendrocyte progenitor fate and differentiation

    PubMed Central

    Wang, Jing; Pol, Suyog U.; Haberman, Alexa K.; Wang, Chunming; O’Bara, Melanie A.; Sim, Fraser J.

    2014-01-01

    Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a+O4+ OPCs relative to CD133+CD140a− neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs. PMID:24982138

  8. Murine mammary stem/progenitor cell isolation: Different method matters?

    PubMed

    Gao, Hui; Dong, Qiaoxiang; Chen, Yuanhong; Zhang, Fuchuang; Wu, Anqi; Shi, Yuanshuo; Bandyopadhyay, Abhik; Daniel, Benjamin J; Huang, Changjiang; Sun, Lu-Zhe

    2016-01-01

    Murine mammary stem/progenitor cell isolation has been routinely used in many laboratories, yet direct comparison among different methods is lacking. In this study, we compared two frequently used digestion methods and three sets of frequently used surface markers for their efficiency in enriching mammary stem and progenitor cells in two commonly used mouse strains, C57BL/6J and FVB. Our findings revealed that the slow overnight digestion method using gentle collagenase/hyaluronidase could be easily adopted and yielded reliable and consistent results in different batches of animals. In contrast, the different fast digestion protocols, as described in published studies, yielded high percent of non-epithelial cells with very few basal epithelial cells liberated in our hands. The three sets of markers tested in our hands reveal rather equally efficiency in separating luminal and basal cells if same fluorochrome conjugations were used. However, the tendency of non-epithelial cell inclusion in the basal cell gate was highest in samples profiled by CD24/CD29 and lowest in samples profiled by CD49f/EpCAM, this is especially true in mammary cells isolated from C57BL/6J mice. This finding will have significant implication when sorted basal cells are used for subsequent gene expression analysis. PMID:26933638

  9. Proliferation and maturation of human erythroid progenitors in liquid culture.

    PubMed

    Fibach, E; Manor, D; Oppenheim, A; Rachmilewitz, E A

    1989-01-01

    Hemopoiesis is studied in vitro mainly in semisolid culture, where hemopoietic progenitors develop into discrete colonies. We describe a liquid culture system that supports the proliferation and maturation of human erythroid progenitors. We seeded mononuclear cells from the peripheral blood (PB) of patients with beta-thalassemia in liquid medium in the presence of conditioned medium from human bladder carcinoma cells. Seven days later, RBCs, normoblasts, granulocytes, and monocytes disappeared, and the number of lymphocytes dropped considerably. In contrast, erythroid colony-forming cells increased fourfold to tenfold. The next step entailed the removal of colony-stimulating factor (CSF) and CSF-secreting cells, the exclusion of macrophages by harvesting nonadherent cells, and the lysis of T lymphocytes by treatment with monoclonal rat antihuman lymphocyte antibodies (CAMPATH-1) and complement. Reculture of the remaining cells in liquid medium supplemented with recombinant erythropoietin (EPO) resulted in the exclusive development of erythroid cells, with myeloid cells reduced to less than 2%. Stainable hemoglobin (Hb) appeared on day 3, with over 85% of the population containing hemoglobin by day 11 and the cell number increasing from 0.2 X 10(6) to 3 X 10(6) mL. By permitting the manipulation of culture conditions and components and increasing the cell yield, the liquid system may facilitate quantitative analysis of growth kinetics as well as biochemical and immunologic characterization of the developing erythroid cell. PMID:2910352

  10. Cis-regulatory mechanisms governing stem and progenitor cell transitions

    PubMed Central

    Johnson, Kirby D.; Kong, Guangyao; Gao, Xin; Chang, Yuan-I; Hewitt, Kyle J.; Sanalkumar, Rajendran; Prathibha, Rajalekshmi; Ranheim, Erik A.; Dewey, Colin N.; Zhang, Jing; Bresnick, Emery H.

    2015-01-01

    Cis-element encyclopedias provide information on phenotypic diversity and disease mechanisms. Although cis-element polymorphisms and mutations are instructive, deciphering function remains challenging. Mutation of an intronic GATA motif (+9.5) in GATA2, encoding a master regulator of hematopoiesis, underlies an immunodeficiency associated with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Whereas an inversion relocalizes another GATA2 cis-element (−77) to the proto-oncogene EVI1, inducing EVI1 expression and AML, whether this reflects ectopic or physiological activity is unknown. We describe a mouse strain that decouples −77 function from proto-oncogene deregulation. The −77−/− mice exhibited a novel phenotypic constellation including late embryonic lethality and anemia. The −77 established a vital sector of the myeloid progenitor transcriptome, conferring multipotentiality. Unlike the +9.5−/− embryos, hematopoietic stem cell genesis was unaffected in −77−/− embryos. These results illustrate a paradigm in which cis-elements in a locus differentially control stem and progenitor cell transitions, and therefore the individual cis-element alterations cause unique and overlapping disease phenotypes. PMID:26601269

  11. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts.

    PubMed

    Liu, Yu; Chen, Li; Diaz, Andrea Diaz; Benham, Ashley; Xu, Xueping; Wijaya, Cori S; Fa'ak, Faisal; Luo, Weijia; Soibam, Benjamin; Azares, Alon; Yu, Wei; Lyu, Qiongying; Stewart, M David; Gunaratne, Preethi; Cooney, Austin; McConnell, Bradley K; Schwartz, Robert J

    2016-01-01

    Mesp1 directs multipotential cardiovascular cell fates, even though it's transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1's transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1(Cre/+); Rosa26(EYFP/+) ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells. PMID:27538477

  12. THE PROGENITOR OF SUPERNOVA 2011dh HAS VANISHED

    SciTech Connect

    Van Dyk, Schuyler D.; Smith, Nathan; Ganeshalingam, Mohan

    2013-08-01

    We conducted Hubble Space Telescope (HST) Snapshot observations of the Type IIb supernova (SN) 2011dh in M51 at an age of {approx}641 days with the Wide Field Camera 3. We find that the yellow supergiant star, clearly detected in pre-SN HST images, has disappeared, implying that this star was almost certainly the progenitor of the SN. Interpretation of the early time SN data which led to the inference of a compact nature for the progenitor, and to the expected survival of this yellow supergiant, is now clearly incorrect. We also present ground-based UBVRI light curves obtained with the Katzman Automatic Imaging Telescope at Lick Observatory up to SN age {approx}70 days. From the light-curve shape including the very late time HST data, and from recent interacting binary models for SN 2011dh, we estimate that a putative surviving companion star to the now deceased yellow supergiant could be detectable by late 2013, especially in the ultraviolet. No obvious light echoes are detectable yet in the SN environment.

  13. Retinal progenitor cells, differentiation, and barriers to cell cycle reentry.

    PubMed

    Davis, Denise M; Dyer, Michael A

    2010-01-01

    Neurogenesis in the retina occurs via the coordination of proliferation, cell cycle exit and differentiation of retinal progenitor cells. Until recently, it was widely assumed that once a retinal progenitor cell produced a postmitotic neuron, there was no possibility for cell-cycle re-entry. However, recent studies have shown that mature differentiated horizontal neurons with reduced Rb pathway function can re-enter the cell cycle and proliferate while maintaining their differentiated features. This chapter will explore the molecular and cellular mechanisms that help to keep differentiated retinal neurons and glia postmitotic. We propose that there are cell-type specific barriers to cell-cycle re-entry by differentiated neurons and these may include apoptosis, chromatin/epigenetics mechanisms, cellular morphology and/or metabolic demands that are distinct across cell populations. Our data suggest that differentiated neurons span a continuum of cellular properties related to their ability to re-enter the cell cycle and undergo cytokinesis while maintaining their differentiated features. A deeper understanding of these processes may allow us to begin to explain the cell type specificity of neuronal cell death and tumor susceptibility. For example, neurons that have more barriers to cell-cycle re-entry may be less likely to form tumors but more likely to undergo degeneration. Conversely, neurons that have fewer barriers to cell-cycle re-entry may be more likely to form tumors but less likely to undergo degeneration. PMID:20959166

  14. Dynamical evolution of the Earth-Moon progenitors - Whence Theia?

    NASA Astrophysics Data System (ADS)

    Quarles, Billy L.; Lissauer, Jack J.

    2015-03-01

    We present integrations of a model Solar System with five terrestrial planets (beginning ∼30-50 Myr after the formation of primitive Solar System bodies) in order to determine the preferred regions of parameter space leading to a Giant Impact that resulted in the formation of the Moon. Our results indicate which choices of semimajor axes and eccentricities for Theia (the proto-Moon) at this epoch can produce a late Giant Impact, assuming that Mercury, Venus, and Mars are near the current orbits. We find that the likely semimajor axis of Theia, at the epoch when our simulations begin, depends on the assumed mass ratio of Earth-Moon progenitors (8/1, 4/1, or 1/1). The low eccentricities of the terrestrial planets are most commonly produced when the progenitors have similar semimajor axes at the epoch when our integrations commence. Additionally, we show that mean motion resonances among the terrestrial planets and perturbations from the giant planets can affect the dynamical evolution of the system leading to a late Giant Impact.

  15. No surviving evolved companions of the progenitor of SN 1006

    NASA Astrophysics Data System (ADS)

    González Hernández, Jonay I.; Ruiz-Lapuente, Pilar; Tabernero, Hugo M.; Montes, David; Canal, Ramon; Méndez, Javier; Bedin, Luigi R.

    2012-09-01

    Type Ia supernovae are thought to occur when a white dwarf made of carbon and oxygen accretes sufficient mass to trigger a thermonuclear explosion. The accretion could be slow, from an unevolved (main-sequence) or evolved (subgiant or giant) star (the single-degenerate channel), or rapid, as the primary star breaks up a smaller orbiting white dwarf (the double-degenerate channel). A companion star will survive the explosion only in the single-degenerate channel. Both channels might contribute to the production of type Ia supernovae, but the relative proportions of their contributions remain a fundamental puzzle in astronomy. Previous searches for remnant companions have revealed one possible case for SN 1572 (refs 8, 9), although that has been questioned. More recently, observations have restricted surviving companions to be small, main-sequence stars, ruling out giant companions but still allowing the single-degenerate channel. Here we report the results of a search for surviving companions of the progenitor of SN 1006 (ref. 14). None of the stars within 4 arc minutes of the apparent site of the explosion is associated with the supernova remnant, and we can firmly exclude all giant and subgiant stars from being companions of the progenitor. In combination with previous results, our findings indicate that fewer than 20 per cent of type Ia supernovae occur through the single-degenerate channel.

  16. A morphological and molecular study of two species of Raphidascaroides Yamaguti, 1941 (Nematoda: Anisakidae), parasites of doradid catfish (Siluriformes) in South America, with a description of R. moraveci n. sp.

    PubMed

    Pereira, Felipe B; Tavares, Luiz E R; Scholz, Tomáš; Luque, José L

    2015-05-01

    Nematodes of the genus Raphidascaroides Yamaguti, 1941 parasitising doradid catfishes (Siluriformes: Doradidae) in Brazil were studied based on morphological and molecular evaluation of newly collected material. A new species, Raphidascaroides moraveci n. sp., is described from the intestine of Platydoras armatulus (Valenciennes) from River Miranda, River Paraguay basin, Pantanal, Mato Grosso do Sul. The new species differs from all of the congeners in having short spicules (163-217 μm in length) representing less than 1% of the total body length and in the posterior region of cloacal opening covered by small rudimentary spines. In addition, it differs from the other congeneric species in the number and arrangement of the caudal papillae and the structure of lips and tail. Raphidascaroides moraveci n. sp. is the third species described from freshwater fishes and the second one in the Neotropical Region. New morphological data on R. brasiliensis Moravec & Thatcher, 1997 from Megalodoras uranoscopus (Eigenmann & Eigenmann) and Platydoras costatus (Linnaeus) (both new host records) from River Xingu, River Amazon basin, Pará, are provided including scanning electron micrographs of taxonomically important structures. The differentiation of the new species is supported by molecular data (partial sequences of the small and large subunits of the rRNA gene). PMID:25862032

  17. Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development

    PubMed Central

    Hartwig, Sunny; Ho, Jacqueline; Pandey, Priyanka; MacIsaac, Kenzie; Taglienti, Mary; Xiang, Michael; Alterovitz, Gil; Ramoni, Marco; Fraenkel, Ernest; Kreidberg, Jordan A.

    2010-01-01

    Summary The Wilms' tumor suppressor 1 (WT1) gene encodes a DNA- and RNA-binding protein that plays an essential role in nephron progenitor differentiation during renal development. To identify WT1 target genes that might regulate nephron progenitor differentiation in vivo, we performed chromatin immunoprecipitation (ChIP) coupled to mouse promoter microarray (ChIP-chip) using chromatin prepared from embryonic mouse kidney tissue. We identified 1663 genes bound by WT1, 86% of which contain a previously identified, conserved, high-affinity WT1 binding site. To investigate functional interactions between WT1 and candidate target genes in nephron progenitors, we used a novel, modified WT1 morpholino loss-of-function model in embryonic mouse kidney explants to knock down WT1 expression in nephron progenitors ex vivo. Low doses of WT1 morpholino resulted in reduced WT1 target gene expression specifically in nephron progenitors, whereas high doses of WT1 morpholino arrested kidney explant development and were associated with increased nephron progenitor cell apoptosis, reminiscent of the phenotype observed in Wt1−/− embryos. Collectively, our results provide a comprehensive description of endogenous WT1 target genes in nephron progenitor cells in vivo, as well as insights into the transcriptional signaling networks controlled by WT1 that might direct nephron progenitor fate during renal development. PMID:20215353

  18. On Measuring the Metallicity of a Type Ia Supernova’s Progenitor

    NASA Astrophysics Data System (ADS)

    Miles, Broxton J.; van Rossum, Daniel R.; Townsley, Dean M.; Timmes, F. X.; Jackson, Aaron P.; Calder, Alan C.; Brown, Edward F.

    2016-06-01

    In Type Ia Supernovae (SNe Ia) the relative abundances of chemical elements are affected by the neutron excess in the composition of the progenitor white dwarf. Since these products leave signatures in the spectra near maximum light, spectral features may be used to constrain the composition of the progenitor. We calculate the nucleosynthetic yields for three SN Ia simulations, assuming single degenerate, Chandrasekhar-mass progenitors, for a wide range of progenitor metallicities, and calculate synthetic light curves and spectra to explore correlations between progenitor metallicity and the strength of spectral features. We use two two-dimensional simulations of the deflagration–detonation–transition scenario with different 56Ni yields and the W7 simulation to control for differences between explosion models and total yields. While the overall yields of intermediate-mass elements (16 < A ≤slant 40) differ between the three cases, trends in the yields are similar. With increasing metallicity, 28Si yields remain nearly constant, 40Ca yields decline, and Ti and 54Fe yields increase. In the synthetic spectra, we identify two features at 30 days post-explosion that appear to deepen with progenitor metallicity: a Ti feature around 4200 Å and an Fe feature around 5200 Å. In all three simulations, their pseudo equivalent widths show a systematic trend with progenitor metallicity. This suggests that these two features may allow for differentiation among progenitor metallicities of observed SNe Ia and potentially help to reduce the intrinsic Hubble scatter.

  19. Regional differences in stem cell/progenitor cell populations from the mouse achilles tendon.

    PubMed

    Mienaltowski, Michael J; Adams, Sheila M; Birk, David E

    2013-01-01

    Specific niches may affect how cells from different regions contribute to tendon biology, particularly in regard to the healing of certain tendinopathies. The objectives of this study are to determine whether distinct subpopulations of stem/progenitor cells are found within the tendon proper and the epi- and paratenon, the peritenon, as well as to characterize these stem/progenitor cell populations. In this study, we hypothesized that tendon stem/progenitor cells exist in each region, that these populations possess distinct features, and that these populations while multipotent could have differing potentials. To test this hypothesis, stem/progenitor cells were isolated and characterized from the peritenon and tendon proper of mouse Achilles tendons. Colony-forming unit and multipotency assays, as well as flow cytometry, and real-time quantitative polymerase chain reaction analyses of stem cell markers were performed. Significantly, more stem/progenitor cell colonies were observed from cells derived from the tendon proper relative to the peritenon. Analysis of surface markers for stem/progenitor cells from both regions indicated that they were Sca1(+) (stem cell marker), Cd90(+) and Cd44(+) (fibroblast markers), Cd18(-) (leukocyte marker), Cd34(-) (hematopoietic and vascular marker), and Cd133(-) (perivascular marker). Tendon proper stem/progenitor cells had increased expression levels for tenomodulin (Tnmd) and scleraxis (Scx), indicative of enrichment of stem/progenitor cells of a tendon origin. In contrast, cells of the peritenon demonstrated relative increases in the vascular (endomucin) and pericyte (Cd133) markers relative to cells from the tendon proper. Stem/progenitor cells from both regions were multipotent (adipogenic, chondrogenic, osteogenic, and tenogenic). These findings demonstrated that different progenitor populations exist within discrete niches of the Achilles tendon-tendon proper versus peritenon. Overall, these data support the hypothesis that

  20. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation

    PubMed Central

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption. PMID:27068606

  1. The Earliest Thymic T Cell Progenitors Sustain B Cell and Myeloid Lineage Potentials

    PubMed Central

    Luc, Sidinh; Luis, Tiago C.; Boukarabila, Hanane; Macaulay, Iain C.; Buza-Vidas, Natalija; Bouriez-Jones, Tiphaine; Lutteropp, Michael; Woll, Petter S.; Loughran, Stephen J.; Mead, Adam J.; Hultquist, Anne; Brown, John; Mizukami, Takuo; Matsuoka, Sahoko; Ferry, Helen; Anderson, Kristina; Duarte, Sara; Atkinson, Deborah; Soneji, Shamit; Domanski, Aniela; Farley, Alison; Sanjuan-Pla, Alejandra; Carella, Cintia; Patient, Roger; de Bruijn, Marella; Enver, Tariq; Nerlov, Claus; Blackburn, Clare; Godin, Isabelle; Jacobsen, Sten Eirik W.

    2012-01-01

    The stepwise commitment from hematopoietic stem cells in the bone marrow (BM) to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage restricted progenitors. However, the commitment stage at which progenitors migrate from the BM to the thymus remains unclear. Here we provide functional and molecular evidence at the single cell level that the earliest progenitors in the neonatal thymus possessed combined granulocyte-monocyte, T and B lymphocyte, but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of thymus-seeding progenitors in the BM, which were closely related at the molecular level. These findings establish the distinct lineage-restriction stage at which the T lineage commitment transits from the BM to the remote thymus. PMID:22344248

  2. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells

    PubMed Central

    Chen, Qi; Zhang, Hui; Liu, Yang; Adams, Susanne; Eilken, Hanna; Stehling, Martin; Corada, Monica; Dejana, Elisabetta; Zhou, Bin; Adams, Ralf H.

    2016-01-01

    Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity. The developmental sources of these cells and molecular mechanisms controlling their progenitors in the heart are only partially understood. Here we show that endocardial endothelial cells are progenitors of pericytes and vascular smooth muscle cells in the murine embryonic heart. Endocardial cells undergo endothelial–mesenchymal transition and convert into primitive mesenchymal progenitors expressing the platelet-derived growth factor receptors, PDGFRα and PDGFRβ. These progenitors migrate into the myocardium, differentiate and assemble the wall of coronary vessels, which requires canonical Wnt signalling involving Frizzled4, β-catenin and endothelial cell-derived Wnt ligands. Our findings identify a novel and unexpected population of progenitors for coronary mural cells with potential relevance for heart function and disease conditions. PMID:27516371

  3. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.

    PubMed

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption. PMID:27068606

  4. Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

    PubMed Central

    Deng, Shengqiong; Zhao, Qian; Zhou, Xianjin; Zhang, Lin; Bao, Luer; Zhen, Lixiao; Zhang, Yuzhen; Fan, Huimin; Liu, Zhongmin; Yu, Zuoren

    2016-01-01

    Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been proven in adult humans. A lower level of miR-708 in c-kit(+) stem/progenitor cells was detected compared to non-progenitors. Overexpression of miR-708 induced cardiomyocyte differentiation of cardiac stem/progenitor cells. This finding strengthened the potential of applying miRNAs in the regeneration of injured hearts, and this indicates that miR-708 could be a novel candidate for treatment of heart diseases. PMID:27338347

  5. Comparative Quantification of the Surfaceome of Human Multipotent Mesenchymal Progenitor Cells

    PubMed Central

    Holley, Rebecca J.; Tai, Guangping; Williamson, Andrew J.K.; Taylor, Samuel; Cain, Stuart A.; Richardson, Stephen M.; Merry, Catherine L.R.; Whetton, Anthony D.; Kielty, Cay M.; Canfield, Ann E.

    2015-01-01

    Summary Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterization of their cell-surface interface limits their clinical exploitation. We have employed subcellular fractionation with quantitative discovery proteomics to define the cell-surface interface proteome of human bone marrow mesenchymal stromal/stem cells (MSCs) and human umbilical cord perivascular cells (HUCPVCs). We compared cell-surface-enriched fractions from MSCs and HUCPVCs (three donors each) with adult mesenchymal fibroblasts using eight-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6,000 proteins with high confidence. This approach identified 186 upregulated mesenchymal progenitor biomarkers. Validation of 10 of these markers, including ROR2, EPHA2, and PLXNA2, confirmed upregulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration, and differentiation. Our approach has delivered a cell-surface proteome repository that now enables improved selection and characterization of human mesenchymal progenitor populations. PMID:25684225

  6. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells.

    PubMed

    Chen, Qi; Zhang, Hui; Liu, Yang; Adams, Susanne; Eilken, Hanna; Stehling, Martin; Corada, Monica; Dejana, Elisabetta; Zhou, Bin; Adams, Ralf H

    2016-01-01

    Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity. The developmental sources of these cells and molecular mechanisms controlling their progenitors in the heart are only partially understood. Here we show that endocardial endothelial cells are progenitors of pericytes and vascular smooth muscle cells in the murine embryonic heart. Endocardial cells undergo endothelial-mesenchymal transition and convert into primitive mesenchymal progenitors expressing the platelet-derived growth factor receptors, PDGFRα and PDGFRβ. These progenitors migrate into the myocardium, differentiate and assemble the wall of coronary vessels, which requires canonical Wnt signalling involving Frizzled4, β-catenin and endothelial cell-derived Wnt ligands. Our findings identify a novel and unexpected population of progenitors for coronary mural cells with potential relevance for heart function and disease conditions. PMID:27516371

  7. Exploring the activated adipogenic niche: interactions of macrophages and adipocyte progenitors.

    PubMed

    Lee, Yun-Hee; Thacker, Robert I; Hall, Brian Eric; Kong, Raymond; Granneman, James G

    2014-01-01

    Adult adipose tissue contains a large supply of progenitors that can renew fat cells for homeostatic tissue maintenance and adaptive growth or regeneration in response to external challenges. However, the in vivo mechanisms that control adipocyte progenitor behavior are poorly characterized. We recently demonstrated that recruitment of adipocyte progenitors by macrophages is a central feature of adipose tissue remodeling under various adipogenic conditions. Catabolic remodeling of white adipose tissue by β3-adrenergic receptor stimulation requires anti-inflammatory M2-polarized macrophages to clear dying adipocytes and to recruit new brown adipocytes from progenitors. In this Extra Views article, we discuss in greater detail the cellular elements of adipogenic niches and report a strategy to isolate and characterize the subpopulations of macrophages and adipocyte progenitors that actively participate in adrenergic tissue remodeling. Further characterization of these subpopulations may facilitate identification of new cellular targets to improve metabolic and immune function of adipose tissue. PMID:24394850

  8. Frontline Science: Splenic progenitors aid in maintaining high neutrophil numbers at sites of sterile chronic inflammation.

    PubMed

    Jhunjhunwala, Siddharth; Alvarez, David; Aresta-DaSilva, Stephanie; Tang, Katherine; Tang, Benjamin C; Greiner, Dale L; Newburger, Peter E; von Andrian, Ulrich H; Langer, Robert; Anderson, Daniel G

    2016-08-01

    Neutrophils are constantly generated from hematopoietic stem and progenitor cells in the bone marrow to maintain high numbers in circulation. A considerable number of neutrophils and their progenitors have been shown to be present in the spleen too; however, their exact role in this organ remains unclear. Herein, we sought to study the function of splenic neutrophils and their progenitors using a mouse model for sterile, peritoneal inflammation. In this microcapsule device implantation model, we show chronic neutrophil presence at implant sites, with recruitment from circulation as the primary mechanism for their prevalence in the peritoneal exudate. Furthermore, we demonstrate that progenitor populations in the spleen play a key role in maintaining elevated neutrophil numbers. Our results provide new insight into the role for splenic neutrophils and their progenitors and establish a model to study neutrophil function during sterile inflammation. PMID:26965635

  9. Progenitor Outgrowth from the Niche in Drosophila Trachea Is Guided by FGF from Decaying Branches

    PubMed Central

    Chen, Feng; Krasnow, Mark A.

    2014-01-01

    Although there has been progress identifying adult stem and progenitor cells and the signals that control their proliferation and differentiation, little is known about the substrates and signals that guide them out of their niche. By examining Drosophila tracheal outgrowth during metamorphosis, we show that progenitors follow a stereotyped path out of the niche, tracking along a subset of tracheal branches destined for destruction. The embryonic tracheal inducer branchless FGF (fibroblast growth factor) is expressed dynamically just ahead of progenitor outgrowth in decaying branches. Knockdown of branchless abrogates progenitor outgrowth, whereas misexpression redirects it. Thus, reactivation of an embryonic tracheal inducer in decaying branches directs outgrowth of progenitors that replace them. This explains how the structure of a newly generated tissue is coordinated with that of the old. PMID:24408434

  10. Progenitor cell maintenance and neurogenesis in sympathetic ganglia involves Notch signaling.

    PubMed

    Tsarovina, Konstantina; Schellenberger, Jens; Schneider, Carolin; Rohrer, Hermann

    2008-01-01

    Differentiation of noradrenergic neurons from neural crest-derived precursors results in the formation of primary sympathetic ganglia. As sympathetic neurons continue to divide after the acquisition of adrenergic and neuronal properties it was unclear, whether the increase in neuron number during neurogenesis is due to neuron proliferation rather than differentiation of progenitor cells. Here, we demonstrate Sox10-positive neural crest progenitor cells and continuous sympathetic neuron generation from Phox2b-positive autonomic progenitors during early chick sympathetic ganglion development. In vivo activation of Notch signaling resulted in a decreased neuronal population, whereas expression of the Notch signaling inhibitor Su(H)(DBM) increased the proportion of Scg10-positive neurons. Similar results were obtained for sensory dorsal root ganglia (DRG). The effects of Notch gain- and loss-of-function experiments support the notion that progenitor maintenance and neuron differentiation from progenitor cells are essential for neurogenesis also during early sympathetic ganglion development. PMID:17920293

  11. Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats.

    PubMed

    Deng, Shengqiong; Zhao, Qian; Zhou, Xianjin; Zhang, Lin; Bao, Luer; Zhen, Lixiao; Zhang, Yuzhen; Fan, Huimin; Liu, Zhongmin; Yu, Zuoren

    2016-01-01

    Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been proven in adult humans. A lower level of miR-708 in c-kit(+) stem/progenitor cells was detected compared to non-progenitors. Overexpression of miR-708 induced cardiomyocyte differentiation of cardiac stem/progenitor cells. This finding strengthened the potential of applying miRNAs in the regeneration of injured hearts, and this indicates that miR-708 could be a novel candidate for treatment of heart diseases. PMID:27338347

  12. Biology of hematopoietic stem cells and progenitors: implications for clinical application.

    PubMed

    Kondo, Motonari; Wagers, Amy J; Manz, Markus G; Prohaska, Susan S; Scherer, David C; Beilhack, Georg F; Shizuru, Judith A; Weissman, Irving L

    2003-01-01

    Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases. PMID:12615892

  13. TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors

    PubMed Central

    Luengo, Mario; Chhatriwala, Mariya; Berry, Andrew; Ponsa-Cobas, Joan; Maestro, Miguel Angel; Jennings, Rachel E.; Pasquali, Lorenzo; Morán, Ignasi; Castro, Natalia; Hanley, Neil A.; Gomez-Skarmeta, Jose Luis; Vallier, Ludovic; Ferrer, Jorge

    2015-01-01

    SUMMARY The genomic regulatory programs that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer, and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic stem cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signaling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signaling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role of TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas. PMID:25915126

  14. TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

    PubMed

    Cebola, Inês; Rodríguez-Seguí, Santiago A; Cho, Candy H-H; Bessa, José; Rovira, Meritxell; Luengo, Mario; Chhatriwala, Mariya; Berry, Andrew; Ponsa-Cobas, Joan; Maestro, Miguel Angel; Jennings, Rachel E; Pasquali, Lorenzo; Morán, Ignasi; Castro, Natalia; Hanley, Neil A; Gomez-Skarmeta, Jose Luis; Vallier, Ludovic; Ferrer, Jorge

    2015-05-01

    The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas. PMID:25915126

  15. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  16. Low- and high-LET radiation drives clonal expansion of lung progenitor cells in vivo.

    PubMed

    Farin, Alicia M; Manzo, Nicholas D; Kirsch, David G; Stripp, Barry R

    2015-01-01

    Abundant populations of epithelial progenitor cells maintain the epithelium along the proximal-to-distal axis of the airway. Exposure of lung tissue to ionizing radiation leads to tissue remodeling and potential cancer initiation or progression. However, little is known about the effects of ionizing radiation on airway epithelial progenitor cells. We hypothesized that ionizing radiation exposure will alter the behavior of airway epithelial progenitor cells in a radiation dose- and quality-dependent manner. To address this hypothesis, we cultured primary airway epithelial cells isolated from mice exposed to various doses of 320 kVp X ray or 600 MeV/nucleon (56)Fe ions in a 3D epithelial-fibroblast co-culture system. Colony-forming efficiency of the airway epithelial progenitor cells was assessed at culture day 14. In vivo clonogenic and proliferative potentials of airway epithelial progenitor cells were measured after exposure to ionizing radiation by lineage tracing and IdU incorporation. Exposure to both X rays and (56)Fe resulted in a dose-dependent decrease in the ability of epithelial progenitors to form colonies in vitro. In vivo evidence for increased clonogenic expansion of epithelial progenitors was observed after exposure to both X rays and (56)Fe. Interestingly, we found no significant increase in the epithelial proliferative index, indicating that ionizing radiation does not promote increased turnover of the airway epithelium. Therefore, we propose a model in which radiation induces a dose-dependent decrease in the pool of available progenitor cells, leaving fewer progenitors able to maintain the airway long-term. This work provides novel insights into the effects of ionizing radiation exposure on airway epithelial progenitor cell behavior. PMID:25564721

  17. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process.

    PubMed

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix-only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications. PMID

  18. Electron-capture supernovae exploding within their progenitor wind

    NASA Astrophysics Data System (ADS)

    Moriya, Takashi J.; Tominaga, Nozomu; Langer, Norbert; Nomoto, Ken'ichi; Blinnikov, Sergei I.; Sorokina, Elena I.

    2014-09-01

    The most massive stars on the asymptotic giant branch (AGB), or the so-called super-AGB stars, are thought to produce supernovae triggered by electron captures in their degenerate O+Ne+Mg cores. Super-AGB stars are expected to have slow winds with high mass-loss rates, so their circumstellar density is high. The explosions of super-AGB stars are therefore presumed to occur in this dense circumstellar environment. We provide the first synthetic light curves for such events by exploding realistic electron-capture supernova progenitors within their super-AGB winds. We find that the early light curve - that is, before the recombination wave reaches the bottom of the hydrogen-rich envelope of supernova ejecta (the plateau phase) - is not affected by the dense wind. However, after the luminosity drop following the plateau phase, the luminosity remains much higher when the super-AGB wind is taken into account. We compare our results to the historical light curve of SN 1054, the progenitor of the Crab Nebula, and show that the explosion of an electron-capture supernova within an ordinary super-AGB wind can explain the observed light curve features. We conclude that SN 1054 could have been a Type IIn supernova without any extra extreme mass loss, which was previously suggested to be necessary to account for its early high luminosity. We also show that our light curves match Type IIn supernovae with an early plateau phase or the so-called Type IIn-P supernovae, and suggest that they are electron-capture supernovae within super-AGB winds. Although some electron-capture supernovae can be bright in the optical spectral range due to the large progenitor radius, their X-ray luminosity from the interaction does not necessarily get as bright as other Type IIn supernovae whose optical luminosities are also powered by the interaction. Thus, we suggest that optically bright X-ray-faint Type IIn supernovae can emerge from electron-capture supernovae. Optically faint Type IIn supernovae

  19. 5-azacytidine promotes terminal differentiation of hepatic progenitor cells.

    PubMed

    He, Yun; Cui, Jiejie; He, Tongchuan; Bi, Yang

    2015-08-01

    5-azacytidine (5-azaC) is known to induce cardiomyocyte differentiation. However, its function in hepatocyte differentiation is unclear. The present study investigated the in vitro capability of 5-azaC to promote maturation and differentiation of mouse embryonic hepatic progenitor cells, with the aim of developing an approach for improving hepatic differentiation. Mouse embryonic hepatic progenitor cells (HP14.5 cells) were treated with 5-azaC at concentrations from 0 to 20 μmol/l, in addition to hepatocyte induction culture medium. Hepatocyte induction medium induces HP14.5 cell differentiation. 5-azaC may enhance the albumin promotor-driven Gaussia luciferase (ALB-GLuc) activity in induced HP14.5 cells. In the present study 2 μmol/l was found to be the optimum concentration with which to achieve this. The expression of hepatocyte-associated factors was not significantly different between the group treated with 5-azaC alone and the control group. The mRNA levels of ALB; cytokeratin 18 (CK18); tyrosine aminotransferase (TAT); and cytochrome p450, family 1, member A1 (CYP1A1); in addition to the protein levels of ALB, CK18 and uridine diphosphate glucuronyltransferase 1A (UGT1A) in the induced group with 5-azaC, were higher than those in the induced group without 5-azaC, although no significant differences were detected in expression of the hepatic stem cell markers, DLK and α-fetoprotein, between the two groups. Treatment with 5-azaC alone did not affect glycogen synthesis or indocyanine green (ICG) metabolic function in HP14.5 cells, although it significantly increased ICG uptake and periodic acid-Schiff-positive cell numbers amongst HP14.5 cells. Therefore, the present study demonstrated that treatment with 5-azaC alone exerted no effects on the maturation and differentiation of HP14.5 cells. However, 5-azaC exhibited a synergistic effect on the terminal differentiation of induced hepatic progenitor cells in association with a hepatic induction medium. PMID

  20. Stromal vascular progenitors in adult human adipose tissue

    PubMed Central

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Pfeifer, Melanie E.; Meyer, E. Michael; Péault, Bruno; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    Background The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Methods Immunohistostaining of intact adipose tissue was used to identify 3 markers (CD31, CD34, CD146) which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90, CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture and tested for adipogenesis. Results The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/α-SMA+/CD90±/CD34−/CD31−; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146−/α-SMA−/CD90+/CD34+/CD31−. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), while small vessel endothelium was CD31+/CD34−/CD90− (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31− pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared to unsorted expanded SVF cells. Conclusions In adipose tissue perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34− pericytes, and the outermost of CD146−/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD

  1. Identification of a T lineage committed progenitor in adult blood

    PubMed Central

    Krueger, Andreas; von Boehmer, Harald

    2007-01-01

    With help of a hCD25 reporter controlled by Ptcra regulatory elements T cell precursors were identified in peripheral blood. Sca-1+, IL-7Rα+, Flt3− precursors that were c-kitlo and Thy-1hi generated T lineage cells when cultured on OP9-DL1 stromal cells and upon transfer into Rag−/−γc−/− mice. No B cells were generated in vivo and only few in vitro. The circulating T cell progenitors (CTP) were found at the same frequency in Foxn1nu/nu thymus deficient mice and wt mice indicating that they were pre- rather than post-thymic, consistent with the observation that inhibition of Notch signaling in vivo did reduce the frequency of intrathymic ETP, but not CTP. Thus, extrathymic T cell commitment is Notch-independent even in adult mice. PMID:17222572

  2. Effects of physical activity on endothelial progenitor cells (EPCs)

    PubMed Central

    De Biase, Chiara; De Rosa, Roberta; Luciano, Rossella; De Luca, Stefania; Capuano, Ernesto; Trimarco, Bruno; Galasso, Gennaro

    2014-01-01

    Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD. PMID:24550833

  3. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    PubMed

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. PMID:24667111

  4. Turning terminally differentiated skeletal muscle cells into regenerative progenitors.

    PubMed

    Wang, Heng; Lööf, Sara; Borg, Paula; Nader, Gustavo A; Blau, Helen M; Simon, András

    2015-01-01

    The ability to repeatedly regenerate limbs during the entire lifespan of an animal is restricted to certain salamander species among vertebrates. This ability involves dedifferentiation of post-mitotic cells into progenitors that in turn form new structures. A long-term enigma has been how injury leads to dedifferentiation. Here we show that skeletal muscle dedifferentiation during newt limb regeneration depends on a programmed cell death response by myofibres. We find that programmed cell death-induced muscle fragmentation produces a population of 'undead' intermediate cells, which have the capacity to resume proliferation and contribute to muscle regeneration. We demonstrate the derivation of proliferating progeny from differentiated, multinucleated muscle cells by first inducing and subsequently intercepting a programmed cell death response. We conclude that cell survival may be manifested by the production of a dedifferentiated cell with broader potential and that the diversion of a programmed cell death response is an instrument to achieve dedifferentiation. PMID:26243583

  5. Proliferation control in neural stem and progenitor cells

    PubMed Central

    Homem, Catarina CF; Repic, Marko; Knoblich, Juergen A

    2015-01-01

    Neural circuit function can be drastically affected by variations in the number of cells that are produced during development or by a reduction in adult cell number due to disease. Unlike many other organs, the brain is unable to compensate for such changes by increasing cell numbers or altering the size of the cells. For this reason, unique cell cycle and cell growth control mechanisms operate in the developing and adult brain. In Drosophila melanogaster and mammalian neural stem and progenitor cells these mechanisms are intricately coordinated with the developmental age and the nutritional, metabolic and hormonal state of the animal. Defects in neural stem cell proliferation that result in the generation of incorrect cell numbers or defects in neural stem cell differentiation can cause microcephaly or megalencephaly. PMID:26420377

  6. Latent progenitor cells as potential regulators for tympanic membrane regeneration

    NASA Astrophysics Data System (ADS)

    Kim, Seung Won; Kim, Jangho; Seonwoo, Hoon; Jang, Kyung-Jin; Kim, Yeon Ju; Lim, Hye Jin; Lim, Ki-Taek; Tian, Chunjie; Chung, Jong Hoon; Choung, Yun-Hoon

    2015-06-01

    Tympanic membrane (TM) perforation, in particular chronic otitis media, is one of the most common clinical problems in the world and can present with sensorineural healing loss. Here, we explored an approach for TM regeneration where the latent progenitor or stem cells within TM epithelial layers may play an important regulatory role. We showed that potential TM stem cells present highly positive staining for epithelial stem cell markers in all areas of normal TM tissue. Additionally, they are present at high levels in perforated TMs, especially in proximity to the holes, regardless of acute or chronic status, suggesting that TM stem cells may be a potential factor for TM regeneration. Our study suggests that latent TM stem cells could be potential regulators of regeneration, which provides a new insight into this clinically important process and a potential target for new therapies for chronic otitis media and other eardrum injuries.

  7. Isolation and Characterization of Distal Lung Progenitor Cells

    PubMed Central

    Driscoll, Barbara; Kikuchi, Alex; Lau, Allison N.; Lee, Jooeun; Reddy, Raghava; Jesudason, Edwin; Kim, Carla F.; Warburton, David

    2013-01-01

    The majority of epithelial cells in the distal lung of rodents and humans are quiescent in vivo, yet certain cell populations retain an intrinsic capacity to proliferate and differentiate in response to lung injury or in appropriate culture settings, thus giving them properties of stem/progenitor cells. Here, we describe the isolation of two such populations from adult mouse lung: alveolar epithelial type 2 cells (AEC2), which can generate alveolar epithelial type 1 cells, and bronchioalveolar stem cells (BASCs), which in culture can reproduce themselves, as well as generate a small number of other distal lung epithelial cell types. These primary epithelial cells are typically isolated using enzyme digestion, mechanical disruption, and serial filtration. AEC2 and BASCs are distinguished from other distal lung cells by expression of specific markers as detected by fluorescence-activated cell sorting, immunohistochemistry, or a combination of both of these techniques. PMID:22610556

  8. Endothelial Progenitor Cells in Sprouting Angiogenesis: Proteases Pave the Way.

    PubMed

    Laurenzana, A; Fibbi, G; Margheri, F; Biagioni, A; Luciani, C; Del Rosso, M; Chillà, A

    2015-01-01

    Sprouting angiogenesis consists of the expansion and remodelling of existing vessels, where the vascular sprouts connect each other to form new vascular loops. Endothelial Progenitor Cells (EPCs) are a subtype of stem cells, with high proliferative potential, able to differentiate into mature Endothelial Cells (ECs) during the neovascularization process. In addition to this direct structural role EPCs improve neovascularization, also secreting numerous pro-angiogenic factors able to enhance the proliferation, survival and function of mature ECs, and other surrounding progenitor cells. While sprouting angiogenesis by mature ECs involves resident ECs, the vasculogenic contribution of EPCs is a high hurdle race. Bone marrowmobilized EPCs have to detach from the stem cell niche, intravasate into bone marrow vessels, reach the hypoxic area or tumour site, extravasate and incorporate into the new vessel lumen, thus complementing the resident mature ECs in sprouting angiogenesis. The goal of this review is to highlight the role of the main protease systems able to control each of these steps. The pivotal protease systems here described, involved in vascular patterning in sprouting angiogenesis, are the matrix-metalloproteinases (MMPs), the serineproteinases urokinase-type plasminogen activator (uPA) associated with its receptor (uPAR) and receptorassociated plasminogen/plasmin, the neutrophil elastase and the cathepsins. Since angiogenesis plays a critical role not only in physiological but also in pathological processes, such as in tumours, controlling the contribution of EPCs to the angiogenic process, through the regulation of the protease systems involved, could yield new opportunities for the therapeutic prospect of efficient control of pathological angiogenesis. PMID:26321757

  9. Functional Genetic Targeting of Embryonic Kidney Progenitor Cells Ex Vivo

    PubMed Central

    Junttila, Sanna; Saarela, Ulla; Halt, Kimmo; Manninen, Aki; Pärssinen, Heikki; Lecca, M. Rita; Brändli, André W.; Sims-Lucas, Sunder; Skovorodkin, Ilya

    2015-01-01

    The embryonic mammalian metanephric mesenchyme (MM) is a unique tissue because it is competent to generate the nephrons in response to Wnt signaling. An ex vivo culture in which the MM is separated from the ureteric bud (UB), the natural inducer, can be used as a classic tubule induction model for studying nephrogenesis. However, technological restrictions currently prevent using this model to study the molecular genetic details before or during tubule induction. Using nephron segment-specific markers, we now show that tubule induction in the MM ex vivo also leads to the assembly of highly segmented nephrons. This induction capacity was reconstituted when MM tissue was dissociated into a cell suspension and then reaggregated (drMM) in the presence of human recombinant bone morphogenetic protein 7/human recombinant fibroblast growth factor 2 for 24 hours before induction. Growth factor–treated drMM also recovered the capacity for organogenesis when recombined with the UB. Cell tracking and time-lapse imaging of chimeric drMM cultures indicated that the nephron is not derived from a single progenitor cell. Furthermore, viral vector-mediated transduction of green fluorescent protein was much more efficient in dissociated MM cells than in intact mesenchyme, and the nephrogenic competence of transduced drMM progenitor cells was preserved. Moreover, drMM cells transduced with viral vectors mediating Lhx1 knockdown were excluded from the nephric tubules, whereas cells transduced with control vectors were incorporated. In summary, these techniques allow reproducible cellular and molecular examinations of the mechanisms behind nephrogenesis and kidney organogenesis in an ex vivo organ culture/organoid setting. PMID:25201883

  10. ECM-Dependence of Endothelial Progenitor Cell Features.

    PubMed

    Siavashi, Vahid; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Vafaei, Rana; Sariri, Reyhaneh

    2016-08-01

    Preserving self-renewal, multipotent capacity, and large-scale expansion of highly functional progenitor cells, including endothelial progenitor cells (EPCs), is a controversial issue. These current limitations, therefore, raise the need of developing promising in vitro conditions for prolonged expansion of EPCs without loss of their stemness feature. In the current study, the possible role of three different natural extracellular substrates, including collagen, gelatin, and fibronectin, on multiple parameters of EPCs such as cell morphology, phenotype, clonogenic, and vasculogenic properties was scrutinized. Next, EPCs from GFP-positive mice were pre-expanded on each of these ECM substrates and then systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. Our results revealed considerable promise for fibronectin for EPC expansion with maintenance of stemness characteristics, whereas gelatin and collagen matrices directed the cells toward a mature endothelial phenotype. Transplantation of EPCs pre-expanded on fibronectin resulted in widespread distribution and appropriate engraftment to various tissues with habitation in close association with the microvasculature. In addition, fibronectin pre-expanded cells were gradually enriched in the bone marrow after transplantation, resulting in marrow repopulation and hematologic recovery, leading to improved survival of recipient mice whereas gelatin- and collagen-expanded cells failed to reconstitute the bone marrow. This study demonstrated that, cell characteristics of in vitro expanded EPCs are determined by the subjacent matrix. Fibronectin-expanded EPCs are heralded as a source of great promise for bone marrow reconstitution and neo-angiogenesis in therapeutic bone marrow transplantation. J. Cell. Biochem. 117: 1934-1946, 2016. © 2016 Wiley Periodicals, Inc. PMID:26756870

  11. Role of stem and progenitor cells in postmyocardial infarction patients.

    PubMed

    Liu, X; Dauwe, D; Patel, A; Janssens, S

    2009-04-01

    Despite state-of-the-art therapy, clinical outcome remains poor in myocardial infarction (MI) patients with reduced left ventricular (LV) function. Stem cell-mediated repair of the damaged heart is a promising new development in cardiovascular medicine. Embryonic stem cells and adult progenitor cells have been extensively studied for their capacity to improve LV function recovery in preclinical MI models but underlying mechanisms remain incompletely understood. Recent placebo-controlled, randomized bone marrow cell transfer trials in MI patients have shown mixed results with cell-mediated effects on global or regional LV function recovery of variable magnitude and duration. There is now growing consensus that the observed effects of bone marrow-(BM)-derived progenitor cell transfer, as applied in post-MI patients thus far, occur independently of cardiomyocyte formation. Subgroup and meta-analysis of currently available randomized and observational pilot trials have highlighted limitations of current cell-based cardiac repair and provided suggestions for future focused clinical trial design. However, the two most recently reported randomized clinical trials failed to confirm a significant biological effect. A better understanding of underlying molecular mechanisms and modalities of cell-based repair is therefore mandatory to facilitate translation of innovative cell-mediated therapies for functional recovery after MI in the years to come. Rapidly growing insights in the biology of cardiac resident cells and technological advances in generation of patient-specific induced pluripotent stem cells may hold great promise to accomplish cardio-myogenesis and directly restore contractile force generation capacity. PMID:19274031

  12. Presence of Stem/Progenitor Cells in the Rat Penis

    PubMed Central

    Lin, Guiting; Zhang, Xiaoyu; Wang, Jianwen; Wang, Lin; Li, Huixi; Wang, Guifang; Ning, Hongxiu; Lin, Ching-Shwun; Xin, Zhongcheng

    2015-01-01

    Tissue resident stem cells are believed to exist in every organ, and their identification is commonly done using a combination of immunostaining for putative stem cell markers and label-retaining cell (LRC) strategy. In this study, we employed these approaches to identify potential stem cells in the penis. Newborn rats were intraperitoneally injected with thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), and their penis was harvested at 7 h, 3 days, 1 week, and 4 weeks. It was processed for EdU stains and immunofluorescence staining for stem cell markers A2B5, PCNA, and c-kit. EdU-positive cells were counted for each time point and co-localized with each stem cell marker, then isolated and cultured in vitro followed by their characterization using flowcytometry and immunofluorescence. At 7 h post-EdU injection, 410±105.3 penile corporal cells were labeled in each cross-section (∼28%). The number of EdU-positive cells at 3 days increased to 536±115.6, while their percentage dropped to 25%. Progressively fewer EdU-positive cells were present in the sacrificed rat penis at longer time points (1 and 4 weeks). They were mainly distributed in the subtunic and perisinusoidal spaces, and defined as subtunic penile progenitor cells (STPCs) and perisinusoidal penile progenitor cells (PPCs). These cells expressed c-kit, A2B5, and PCNA. After culturing in vitro, only ∼0.324% corporal cells were EdU-labeled LRCs and expressed A2B5/PCNA. Therefore, labeling of penis cells by EdU occurred randomly, and label retaining was not associated with expression of c-kit, A2B5, or PCNA. The penile LRCs are mainly distributed within the subtunic and perisinusoidal space. PMID:25162971

  13. C/EBPalpha directs monocytic commitment of primary myeloid progenitors.

    PubMed

    Wang, Dehua; D'Costa, Jenice; Civin, Curt I; Friedman, Alan D

    2006-08-15

    C/EBPalpha is required for generation of granulocyte-monocyte progenitors, but the subsequent role of C/EBPalpha in myeloid lineage commitment remains uncertain. We transduced murine marrow cells with C/EBPalpha-estradiol receptor (ER) or empty vector and subjected these to lineage depletion just prior to culture in estradiol with myeloid cytokines. This protocol limits biases due to lineage-specific effects on developmental kinetics, proliferation, and apoptosis. Also, lowering the dose of estradiol reduced activated C/EBPalpha-ER to near the physiologic range. C/EBPalpha-ER increased Mac1(+)/Gr1(-)/MPO(-)/low monocytes 1.9-fold while reducing Mac1(+)/Gr1(+)/MPO(hi) granulocytes 2.5-fold at 48 hours, even in 0.01 microM estradiol. This pattern was confirmed morphologically and by quantitative polymerase chain reaction (PCR) assay of lineage markers. To directly assess effects on immature progenitors, transduced cells were cultured for 1 day with and then in methylcellulose without estradiol. A 2-fold increase in monocytic compared with granulocytic colonies was observed in IL-3/IL-6/SCF or GM-CSF, but not G-CSF, even in 0.01 microM estradiol. C/EBPalpha-ER induced PU.1 mRNA, and PU.1-ER stimulated monocytic development, suggesting that transcriptional induction of PU.1 by C/EBPalpha contributes to monopoiesis. A C/EBPalpha variant incapable of zippering with c-Jun did not induce monopoiesis, and a variant unable to bind NF-kappaB p50 stimulated granulopoiesis, suggesting their cooperation with C/EBPalpha during monocytic commitment. PMID:16645168

  14. The development of zebrafish tendon and ligament progenitors.

    PubMed

    Chen, Jessica W; Galloway, Jenna L

    2014-05-01

    Despite the importance of tendons and ligaments for transmitting movement and providing stability to the musculoskeletal system, their development is considerably less well understood than that of the tissues they serve to connect. Zebrafish have been widely used to address questions in muscle and skeletal development, yet few studies describe their tendon and ligament tissues. We have analyzed in zebrafish the expression of several genes known to be enriched in mammalian tendons and ligaments, including scleraxis (scx), collagen 1a2 (col1a2) and tenomodulin (tnmd), or in the tendon-like myosepta of the zebrafish (xirp2a). Co-expression studies with muscle and cartilage markers demonstrate the presence of scxa, col1a2 and tnmd at sites between the developing muscle and cartilage, and xirp2a at the myotendinous junctions. We determined that the zebrafish craniofacial tendon and ligament progenitors are neural crest derived, as in mammals. Cranial and fin tendon progenitors can be induced in the absence of differentiated muscle or cartilage, although neighboring muscle and cartilage are required for tendon cell maintenance and organization, respectively. By contrast, myoseptal scxa expression requires muscle for its initiation. Together, these data suggest a conserved role for muscle in tendon development. Based on the similarities in gene expression, morphology, collagen ultrastructural arrangement and developmental regulation with that of mammalian tendons, we conclude that the zebrafish tendon populations are homologous to their force-transmitting counterparts in higher vertebrates. Within this context, the zebrafish model can be used to provide new avenues for studying tendon biology in a vertebrate genetic system. PMID:24803652

  15. Circulating endothelial cells and their progenitors in acute myeloid leukemia

    PubMed Central

    Zahran, Asmaa Mohammed; Aly, Sanaa Shaker; Altayeb, Hanan Ahmed; Ali, Arwa Mohammed

    2016-01-01

    Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management. PMID:27602121

  16. How do I perform hematopoietic progenitor cell selection?

    PubMed

    Avecilla, Scott T; Goss, Cheryl; Bleau, Sharon; Tonon, Jo-Ann; Meagher, Richard C

    2016-05-01

    Graft-versus-host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T-cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high-affinity anti-CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%-100%) and consistent 3-log CD3+ T-cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures. PMID:26919388

  17. Supernova Rates, Rise-Times, and their Relations to Progenitors

    NASA Astrophysics Data System (ADS)

    Gonzalez Gaitan, Santiago

    Supernovae are fundamental in astronomy: they inject high mass elements into the interstellar medium enriching the chemistry of galaxies, they feed processes of star formation and active galactic nuclei, and they have been a key for the developments in cosmology of the past decades. This dissertation presents a set of subluminous type Ia supernovae (SNe Ia) at z > 0.1 from the Supernova Legacy Survey (SNLS). These faint and short-lived transients are found in massive and passive host galaxies. We measure a volumetric rate as a function of redshift that is different from the normal SN Ia population. The observations point towards a long delay time since the birth of the progenitors systems and argue for progenitor stars of initial low mass. We calculate a stretch-corrected rise-time since explosion to maximum brightness for different sets of SNe Ia. We find that a fiducial 17 day quadratic rise is sufficient to explain all SNe Ia, including subluminous ones, arguing for their homogeneity throughout the entire light-curve. Subluminous SNe Ia are powered by as little as 0.05 solar masses of radioactive nickel synthesized in the explosion. Theoretical models need to explain these challenging weak explosions within the framework of SNe Ia. Finally, we develop one of the first robust automated techniques to identify plateau supernovae (SNe IIP) in large photometric transient surveys. This simple method was tested with a variety of real and simulated SN samples and proved to be effective across different redshifts. Such a photometric typing will be of great power for coming surveys and will allow numerous scientific studies of SNe IIP.

  18. Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia

    PubMed Central

    Dong, Yu; Sun, Qi; Liu, Teng; Wang, Huanyuan; Jiao, Kun; Xu, Jiahui; Liu, Xin; Liu, Huirong; Wang, Wen

    2016-01-01

    In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that

  19. Antidepressants increase neural progenitor cells in the human hippocampus

    PubMed Central

    Boldrini, Maura; Underwood, Mark D.; Hen, René; Rosoklija, Gorazd B.; Dwork, Andrew J.; Mann, J. John; Arango, Victoria

    2009-01-01

    Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) increase neurogenesis in the dentate gyrus (DG) of rodents and nonhuman primates. We determined whether SSRIs or TCAs increase neural progenitor (NPCs) and dividing cells in the human DG in major depressive disorder (MDD). Whole frozen hippocampi from untreated subjects with MDD (N = 5), antidepressant-treated MDD (MDDT, N = 7), and controls (C, N = 7) were fixed, sectioned and immunostained for NPCs and dividing cell markers (nestin and Ki-67 respectively), NeuN and GFAP, in single and double labeling. NPC and dividing cell numbers in the DG were estimated by stereology. Clinical data were obtained by psychological autopsy and toxicological and neuropathological examination performed in all subjects. NPCs decreased with age (p = 0.034). Females had more NPCs than males (p = 0.023). Correcting for age and sex, MDDT receiving SSRIs had more NPCs than untreated MDD (p ≤ 0.001) and controls (p ≤ 0.001), NPCs were not different in SSRIs- and TCAs-treated MDDT (p = 0.169). Dividing cell number, unaffected by age or sex, was greater in MDDT receiving TCAs than in untreated MDD (p ≤ 0.001), SSRI-treated MDD (p = 0.001) and controls (p ≤ 0.001). The NPCs and dividing cells increase in MDDT was localized to the rostral DG. MDDT had a larger DG volume compared with untreated MDD or controls (p = 0.009). Antidepressants increase neural progenitor cell number in the anterior human dentate gyrus. Whether this finding is critical or necessary for the antidepressants effect remains to be determined. PMID:19606083

  20. TLR2 Activation Inhibits Embryonic Neural Progenitor Cell Proliferation

    PubMed Central

    Okun, Eitan; Griffioen, Kathleen J.; Gen-Son, Tae; Lee, Jong-Hwan; Roberts, Nicholas J.; Mughal, Mohamed R.; Hutchison, Emmette; Cheng, Aiwu; Arumugam, Thiruma V.; Lathia, Justin D.; van Praag, Henriette; Mattson, Mark P.

    2010-01-01

    Toll-like receptors (TLRs) play essential roles in innate immunity, and increasing evidence indicates that these receptors are expressed in neurons, astrocytes and microglia in the brain, where they mediate responses to infection, stress and injury. To address the possibility that TLR2 heterodimer activation could affect progenitor cells in the developing brain, we analyzed the expression of TLR2 throughout the mouse cortical development, and assessed the role of TLR2 heterodimer activation in neural progenitor cell (NPC) proliferation. TLR2 mRNA and protein was expressed in the cortex in embryonic and early postnatal stages of development, and in cultured cortical NPC. While NPC from TLR2-deficient and wild type embryos had the same proliferative capacity, TLR2 activation by the synthetic bacterial lipopeptides Pam3CSK4 and FSL1, or low molecular weight hyaluronan, an endogenous ligand for TLR2, inhibited neurosphere formation in vitro. Intracerebral in utero administration of TLR2 ligands resulted in ventricular dysgenesis characterized by increased ventricle size, reduced proliferative area around the ventricles, increased cell density, an increase in PH3+ cells and a decrease in BrdU+ cells in the sub-ventricular zone. Our findings indicate that loss of TLR2 does not result in defects in cerebral development. However, TLR2 is expressed and functional in the developing telencephalon from early embryonic stages and infectious agent-related activation of TLR2 inhibits NPC proliferation. TLR2–mediated inhibition of NPC proliferation may therefore be a mechanism by which infection, ischemia and inflammation adversely affect brain development. PMID:20456021

  1. Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia.

    PubMed

    Dong, Yu; Sun, Qi; Liu, Teng; Wang, Huanyuan; Jiao, Kun; Xu, Jiahui; Liu, Xin; Liu, Huirong; Wang, Wen

    2016-01-01

    In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that

  2. MicroRNA-194 Regulates Hepatocytic Differentiation of Progenitor Cells by Targeting YAP1

    PubMed Central

    Jung, Kwang Hwa; McCarthy, Ryan L.; Zhou, Chong; Uprety, Nadima; Barton, Michelle Craig; Beretta, Laura

    2015-01-01

    MicroRNA expression profiling in human liver progenitor cells following hepatocytic differentiation identified miR-122 and miR-194 as the microRNAs most strongly upregulated during hepatocytic differentiation of progenitor cells. MiR-194 was also highly upregulated following hepatocytic differentiation of human embryonic stem cells (hESCs). Overexpression of miR-194 in progenitor cells accelerated their differentiation into hepatocytes, as measured by morphological features such as canaliculi and expression of hepatocytic markers. Overexpression of miR-194 in hESCs induced their spontaneous differentiation, a phenotype accompanied with accelerated loss of the pluripotent factors OCT4 and NANOG and decrease in mesoderm marker HAND1 expression. We then identified YAP1 as a direct target of miR-194. Inhibition of YAP1 strongly induced hepatocytic differentiation of progenitor cells and YAP1 over expression reversed the miR-194-induced hepatocytic differentiation of progenitor cells. In conclusion, we identified miR-194 as a potent inducer of hepatocytic differentiation of progenitor cells and further identified YAP1 as a mediator of miR-194's effects on hepatocytic differentiation and liver progenitor cell fate. PMID:26731713

  3. The death of massive stars - II. Observational constraints on the progenitors of Type Ibc supernovae

    NASA Astrophysics Data System (ADS)

    Eldridge, John J.; Fraser, Morgan; Smartt, Stephen J.; Maund, Justyn R.; Crockett, R. Mark

    2013-11-01

    The progenitors of many Type II core-collapse supernovae (SNe) have now been identified directly on pre-discovery imaging. Here, we present an extensive search for the progenitors of Type Ibc SNe in all available pre-discovery imaging since 1998. There are 12 Type Ibc SNe with no detections of progenitors in either deep ground-based or Hubble Space Telescope archival imaging. The deepest absolute BVR magnitude limits are between -4 and - 5 mag. We compare these limits with the observed Wolf-Rayet population in the Large Magellanic Cloud and estimate a 16 per cent probability that we have failed to detect such a progenitor by chance. Alternatively, the progenitors evolve significantly before core-collapse or we have underestimated the extinction towards the progenitors. Reviewing the relative rates and ejecta mass estimates from light-curve modelling of Ibc SNe, we find both incompatible with Wolf-Rayet stars with initial masses >25 M⊙ being the only progenitors. We present binary evolution models that fit these observational constraints. Stars in binaries with initial masses ≲ 20 M⊙ lose their hydrogen envelopes in binary interactions to become low-mass helium stars. They retain a low-mass hydrogen envelope until ≈104 yr before core-collapse; hence, it is not surprising that Galactic analogues have been difficult to identify.

  4. Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration

    PubMed Central

    Carpino, Guido; Renzi, Anastasia; Franchitto, Antonio; Cardinale, Vincenzo; Onori, Paolo; Reid, Lola; Alvaro, Domenico; Gaudio, Eugenio

    2016-01-01

    Niches containing stem/progenitor cells are present in different anatomical locations along the human biliary tree and within liver acini. The most primitive stem/progenitors, biliary tree stem/progenitor cells (BTSCs), reside within peribiliary glands located throughout large extrahepatic and intrahepatic bile ducts. BTSCs are multipotent and can differentiate towards hepatic and pancreatic cell fates. These niches' matrix chemistry and other characteristics are undefined. Canals of Hering (bile ductules) are found periportally and contain hepatic stem/progenitor cells (HpSCs), participating in the renewal of small intrahepatic bile ducts and being precursors to hepatocytes and cholangiocytes. The niches also contain precursors to hepatic stellate cells and endothelia, macrophages, and have a matrix chemistry rich in hyaluronans, minimally sulfated proteoglycans, fetal collagens, and laminin. The microenvironment furnishes key signals driving HpSC activation and differentiation. Newly discovered third niches are pericentral within hepatic acini, contain Axin2+ unipotent hepatocytic progenitors linked on their lateral borders to endothelia forming the central vein, and contribute to normal turnover of mature hepatocytes. Their relationship to the other stem/progenitors is undefined. Stem/progenitor niches have important implications in regenerative medicine for the liver and biliary tree and in pathogenic processes leading to diseases of these tissues. PMID:26880956

  5. Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment

    PubMed Central

    Mu, Xueru; Español-Suñer, Regina; Mederacke, Ingmar; Affò, Silvia; Manco, Rita; Sempoux, Christine; Lemaigre, Frédéric P.; Adili, Arlind; Yuan, Detian; Weber, Achim; Unger, Kristian; Heikenwälder, Mathias; Leclercq, Isabelle A.; Schwabe, Robert F.

    2015-01-01

    In many organs, including the intestine and skin, cancers originate from cells of the stem or progenitor compartment. Despite its nomenclature, the cellular origin of hepatocellular carcinoma (HCC) remains elusive. In contrast to most organs, the liver lacks a defined stem cell population for organ maintenance. Previous studies suggest that both hepatocytes and facultative progenitor cells within the biliary compartment are capable of generating HCC. As HCCs with a progenitor signature carry a worse prognosis, understanding the origin of HCC is of clinical relevance. Here, we used complementary fate-tracing approaches to label the progenitor/biliary compartment and hepatocytes in murine hepatocarcinogenesis. In genotoxic and genetic models, HCCs arose exclusively from hepatocytes but never from the progenitor/biliary compartment. Cytokeratin 19–, A6- and α-fetoprotein–positive cells within tumors were hepatocyte derived. In summary, hepatocytes represent the cell of origin for HCC in mice, and a progenitor signature does not reflect progenitor origin, but dedifferentiation of hepatocyte-derived tumor cells. PMID:26348897

  6. The Hemogenic Competence of Endothelial Progenitors Is Restricted by Runx1 Silencing during Embryonic Development.

    PubMed

    Eliades, Alexia; Wareing, Sarah; Marinopoulou, Elli; Fadlullah, Muhammad Z H; Patel, Rahima; Grabarek, Joanna B; Plusa, Berenika; Lacaud, Georges; Kouskoff, Valerie

    2016-06-01

    It is now well-established that hematopoietic stem cells (HSCs) and progenitor cells originate from a specialized subset of endothelium, termed hemogenic endothelium (HE), via an endothelial-to-hematopoietic transition. However, the molecular mechanisms determining which endothelial progenitors possess this hemogenic potential are currently unknown. Here, we investigated the changes in hemogenic potential in endothelial progenitors at the early stages of embryonic development. Using an ETV2::GFP reporter mouse to isolate emerging endothelial progenitors, we observed a dramatic decrease in hemogenic potential between embryonic day (E)7.5 and E8.5. At the molecular level, Runx1 is expressed at much lower levels in E8.5 intra-embryonic progenitors, while Bmi1 expression is increased. Remarkably, the ectopic expression of Runx1 in these progenitors fully restores their hemogenic potential, as does the suppression of BMI1 function. Altogether, our data demonstrate that hemogenic competency in recently specified endothelial progenitors is restrained through the active silencing of Runx1 expression. PMID:27239041

  7. Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning

    PubMed Central

    Bayindir, Irem; Babaeikelishomi, Rohollah; Kocanova, Silvia; Sousa, Isabel Sofia; Lerch, Sarah; Hardt, Olaf; Wild, Stefan; Bosio, Andreas; Bystricky, Kerstin; Herzig, Stephan; Vegiopoulos, Alexandros

    2015-01-01

    De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation. PMID:26347713

  8. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish

    PubMed Central

    Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

    2015-01-01

    Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration. PMID:26630262

  9. Syndecan 4 Mediates Nrf2-dependent Expansion of Bronchiolar Progenitors That Protect Against Lung Inflammation

    PubMed Central

    Santoso, Arif; Kikuchi, Toshiaki; Tode, Naoki; Hirano, Taizou; Komatsu, Riyo; Damayanti, Triya; Motohashi, Hozumi; Yamamoto, Masayuki; Kojima, Tetsuhito; Uede, Toshimitsu; Nukiwa, Toshihiro; Ichinose, Masakazu

    2016-01-01

    The use of lung progenitors for regenerative medicine appears promising, but their biology is not fully understood. Here, we found anti-inflammatory attributes in bronchiolar progenitors that were sorted as a multipotent subset of mouse club cells and found to express secretory leukocyte protease inhibitor (SLPI). Notably, the impaired expression of SLPI in mice increased the number of bronchiolar progenitors and decreased the lung inflammation. We determined a transcriptional profile for the bronchiolar progenitors of Slpi-deficient mice and identified syndecan 4, whose expression was markedly elevated as compared to that of wild-type mice. Systemic administration of recombinant syndecan 4 protein caused a substantial increase in the number of bronchiolar progenitors with concomitant attenuation of both airway and alveolar inflammation. The syndecan 4 administration also resulted in activation of the Keap1-Nrf2 antioxidant pathway in lung cells, which is critically involved in the therapeutic responses to the syndecan 4 treatment. Moreover, in 3D culture, the presence of syndecan 4 induced differentiated club cells to undergo Nrf2-dependent transition into bronchiolar progenitors. Our observations reveal that differentiative switches between bronchiolar progenitors and club cells are under the Nrf2-mediated control of SLPI and syndecan 4, suggesting the possibility of new therapeutic approaches in inflammatory lung diseases. PMID:26307669

  10. Motor neurons and oligodendrocytes arise from distinct cell lineages by progenitor recruitment

    PubMed Central

    Ravanelli, Andrew M.; Appel, Bruce

    2015-01-01

    During spinal cord development, ventral neural progenitor cells that express the transcription factors Olig1 and Olig2, called pMN progenitors, produce motor neurons and then oligodendrocytes. Whether motor neurons and oligodendrocytes arise from common or distinct progenitors in vivo is not known. Using zebrafish, we found that motor neurons and oligodendrocytes are produced sequentially by distinct progenitors that have distinct origins. When olig2+ cells were tracked during the peak period of motor neuron formation, most differentiated as motor neurons without further cell division. Using time-lapse imaging, we found that, as motor neurons differentiated, more dorsally positioned neuroepithelial progenitors descended to the pMN domain and initiated olig2 expression. Inhibition of Hedgehog signaling during motor neuron differentiation blocked the ventral movement of progenitors, the progressive initiation of olig2 expression, and oligodendrocyte formation. We therefore propose that the motor neuron-to-oligodendrocyte switch results from Hedgehog-mediated recruitment of glial-fated progenitors to the pMN domain subsequent to neurogenesis. PMID:26584621

  11. Characterization of interstitial Cajal progenitors cells and their changes in Hirschsprung's disease.

    PubMed

    Chen, Zhi-Hua; Zhang, Yong-Chang; Jiang, Wei-Fang; Yang, Cissy; Zou, Gang-Ming; Kong, Yu; Cai, Wei

    2014-01-01

    Interstitial cells of Cajal (ICC) are critical to gastrointestinal motility. The phenotypes of ICC progenitors have been observed in the mouse gut, but whether they exist in the human colon and what abnormal changes in their quantity and ultrastructure are present in Hirschsprung's disease (HSCR) colon remains uncertain. In this study, we collected the surgical resection of colons, both proximal and narrow segments, from HSCR patients and normal controls. First, we identified the progenitor of ICC in normal adult colon using immunofluorescent localization techniques with laser confocal microscopy. Next, the progenitors were sorted to observe their morphology. We further applied flow cytometry to examine the content of ICC progenitors in these fresh samples. The ultrastructural changes in the narrow and proximal parts of the HSCR colon were observed using transmission electron microscopy (TEM) and were compared with the normal adult colon. The presumed early progenitor (c-Kit(low)CD34(+)Igf1r(+)) and committed progenitor (c-Kit(+)CD34(+)Igf1r(+)) of ICC exist in adult normal colon as well as in the narrow and proximal parts of the HSCR colon. However, the proportions of mature, early and committed progenitors of ICC were dramatically reduced in the narrow segment of the HSCR colon. The proportions of mature and committed progenitors of ICC in the proximal segment of the HSCR colon were lower than in the adult normal colon. Ultrastructurally, ICC, enteric nerves, and smooth muscle in the narrow segment of the HSCR colon showed severe injury, including swollen vacuola or ted mitochondria, disappearance of mitochondrial cristae, dilated rough endoplasmic reticulum, vesiculation and degranulation, and disappearance of the caveolae on the ICC membrane surface. The contents of ICC and its progenitors in the narrow part of the HSCR colon were significantly decreased than those of adult colon, which may be associated with HSCR pathogenesis. PMID:24475076

  12. Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth

    PubMed Central

    Tomita, Mayumi; Asada, Misako; Asada, Nariaki; Nakamura, Jin; Oguchi, Akiko; Higashi, Atsuko Y.; Endo, Shuichiro; Robertson, Elizabeth; Kimura, Takeshi; Kita, Toru; Economides, Aris N.; Kreidberg, Jordan; Yanagita, Motoko

    2013-01-01

    The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth. PMID:23991197

  13. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  14. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  15. Heterogeneity of neural progenitor cells revealed by enhancers in the nestin gene

    PubMed Central

    Yaworsky, Paul J.; Kappen, Claudia

    2014-01-01

    Using transgenic embryos, we have identified two distinct CNS progenitor cell-specific enhancers, each requiring the cooperation of at least two independent regulatory sites, within the second intron of the rat nestin gene. One enhancer is active throughout the developing CNS while the other is specifically active in the ventral midbrain. These experiments demonstrate that neural progenitor cells in the midbrain constitute a unique subpopulation based upon their ability to activate the midbrain regulatory elements. Our finding of differential enhancer activity from a gene encoding a structural protein reveals a previously unrecognized diversity in neural progenitor cell populations. PMID:9917366

  16. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  17. Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart.

    PubMed

    Fuentes, Tania I; Appleby, Nancy; Raya, Michael; Bailey, Leonard; Hasaniya, Nahidh; Stodieck, Louis; Kearns-Jonker, Mary

    2015-01-01

    Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of

  18. Using SN 1987A light echoes to determine mass loss from the progenitor

    NASA Technical Reports Server (NTRS)

    Crotts, Arlin P. S.; Kunkel, William E.

    1991-01-01

    The hypothesis that the blue progenitor of SN 1987A passed through a blue supergiant phase ending with the expulsion of the outer envelope is tested. The many light echoes seen near SN 1987A were used to search for a mass flow from the progenitor and for abrupt density changes at the limits of this smooth mass flow. The progenitor needed roughly a million yr to create these structures, assuming a constant mass loss at 15 km/s. The dust in the region is small-grained and isotropically scattering. Interaction between the progenitor blue supergiant and red supergiant winds is probably contained within a roughly spherical structure 1.5 pc in diameter.

  19. Regulation of cerebral cortex size and folding by expansion of basal progenitors

    PubMed Central

    Nonaka-Kinoshita, Miki; Reillo, Isabel; Artegiani, Benedetta; Ángeles Martínez-Martínez, Maria; Nelson, Mark; Borrell, Víctor; Calegari, Federico

    2013-01-01

    Size and folding of the cerebral cortex increased massively during mammalian evolution leading to the current diversity of brain morphologies. Various subtypes of neural stem and progenitor cells have been proposed to contribute differently in regulating thickness or folding of the cerebral cortex during development, but their specific roles have not been demonstrated. We report that the controlled expansion of unipotent basal progenitors in mouse embryos led to megalencephaly, with increased surface area of the cerebral cortex, but not to cortical folding. In contrast, expansion of multipotent basal progenitors in the naturally gyrencephalic ferret was sufficient to drive the formation of additional folds and fissures. In both models, changes occurred while preserving a structurally normal, six-layered cortex. Our results are the first experimental demonstration of specific and distinct roles for basal progenitor subtypes in regulating cerebral cortex size and folding during development underlying the superior intellectual capability acquired by higher mammals during evolution. PMID:23624932

  20. Murine Mueller cells are progenitor cells for neuronal cells and fibrous tissue cells

    SciTech Connect

    Florian, Christian; Langmann, Thomas; Weber, Bernhard H.F.; Morsczeck, Christian

    2008-09-19

    Mammalian Mueller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates murine Mueller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Mueller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markers were differentially expressed. In contrast, aged Mueller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after cultivation on laminin/ornithine cell culture substrate. Here, we report for the first time that murine Mueller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture.

  1. Immortalization and Characterization of Lineage-restricted Neuronal Progenitor Cells Derived From the Procine Olfactory Bulb

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crucial aspects in the development of in vitro neuropathogenic disease model systems are the identification, characterization, and continuous mitotic expansion of cultured neuronal cells. To facilitate long-term cultivation, we immortalized cultured porcine olfactory neuronally restricted progenitor...

  2. Exercise-Induced Skeletal Muscle Adaptations Alter the Activity of Adipose Progenitor Cells

    PubMed Central

    Graff, Jonathan M.

    2016-01-01

    Exercise decreases adiposity and improves metabolic health; however, the physiological and molecular underpinnings of these phenomena remain unknown. Here, we investigate the effect of endurance training on adipose progenitor lineage commitment. Using mice with genetically labeled adipose progenitors, we show that these cells react to exercise by decreasing their proliferation and differentiation potential. Analyses of mouse models that mimic the skeletal muscle adaptation to exercise indicate that muscle, in a non-autonomous manner, regulates adipose progenitor homeostasis, highlighting a role for muscle-derived secreted factors. These findings support a humoral link between skeletal muscle and adipose progenitors and indicate that manipulation of adipose stem cell function may help address obesity and diabetes. PMID:27015423

  3. Exercise-Induced Skeletal Muscle Adaptations Alter the Activity of Adipose Progenitor Cells.

    PubMed

    Zeve, Daniel; Millay, Douglas P; Seo, Jin; Graff, Jonathan M

    2016-01-01

    Exercise decreases adiposity and improves metabolic health; however, the physiological and molecular underpinnings of these phenomena remain unknown. Here, we investigate the effect of endurance training on adipose progenitor lineage commitment. Using mice with genetically labeled adipose progenitors, we show that these cells react to exercise by decreasing their proliferation and differentiation potential. Analyses of mouse models that mimic the skeletal muscle adaptation to exercise indicate that muscle, in a non-autonomous manner, regulates adipose progenitor homeostasis, highlighting a role for muscle-derived secreted factors. These findings support a humoral link between skeletal muscle and adipose progenitors and indicate that manipulation of adipose stem cell function may help address obesity and diabetes. PMID:27015423

  4. Innate lymphoid cell development requires TOX-dependent generation of a common ILC progenitor

    PubMed Central

    Seehus, Corey R.; Aliahmad, Parinaz; de la Torre, Brian; Iliev, Iliyan D.; Spurka, Lindsay; Funari, Vincent A.; Kaye, Jonathan

    2015-01-01

    Diverse innate lymphoid cell (ILC) subtypes have been defined, based on effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways leading to ILC lineage specification remain poorly characterized. Here we demonstrate that transcriptional regulator TOX is required for the in vivo differentiation of common lymphoid progenitors to ILC lineage-restricted cells. In vitro modeling demonstrates that TOX deficiency results in early defects in progenitor cell survival or expansion as well as later stage ILC differentiation. In addition, comparative transcriptome analysis of bone marrow progenitors reveals that TOX-deficient cells fail to upregulate many aspects of the ILC gene program, including Notch gene targets, implicating TOX as a key determinant of early ILC lineage specification. PMID:25915732

  5. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

    PubMed Central

    Farha, Samar; Lichtin, Alan; Graham, Brian; George, Deepa; Aldred, Micheala; Hazen, Stanley L.; Loyd, James; Tuder, Rubin

    2012-01-01

    Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. PMID:22745307

  6. ON THE PROGENITOR OF THE TYPE II-PLATEAU SN 2008cn in NGC 4603

    SciTech Connect

    Elias-Rosa, Nancy; Van Dyk, Schuyler D.; Li, Weidong; Filippenko, Alexei V.; Foley, Ryan J.; Smith, Nathan; Morrell, Nidia; Gonzalez, Sergio; Hamuy, Mario; Cuillandre, Jean-Charles E-mail: vandyk@ipac.caltech.ed

    2009-12-01

    A trend is emerging regarding the progenitor stars that give rise to the most common core-collapse supernovae (SNe), those of Type II-Plateau (II-P): they generally appear to be red supergiants with a limited range of initial masses, approx8-16 M{sub sun}. Here, we consider another example, SN 2008cn, in the nearly face-on spiral galaxy NGC 4603. Even with limited photometric data, it appears that SN 2008cn is not a normal SN II-P, but is of the high-luminosity subclass. Through comparison of pre- and post-explosion images obtained with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope, we have isolated a supergiant star prior to explosion at nearly the same position as the SN. We provide evidence that this supergiant may well be the progenitor of the SN, although this identification is not entirely unambiguous. This is exacerbated by the distance to the host galaxy, 33.3 Mpc, making SN 2008cn the most distant SN II-P yet for which an attempt has been made to identify a progenitor star in pre-SN images. The progenitor candidate has a more yellow color ([V - I]{sub 0} = 0.98 mag and T {sub eff} = 5200 +- 300 K) than generally would be expected and, if a single star, would require that it exploded during a 'blue loop' evolutionary phase, which is theoretically not expected to occur. Nonetheless, we estimate an initial mass of M{sub ini} = 15 +- 2 M{sub sun} for this star, which is within the expected mass range for SN II-P progenitors. The yellower color could also arise from the blend of two or more stars, such as a red supergiant and a brighter, blue supergiant. Such a red supergiant hidden in this blend could instead be the progenitor and would also have an initial mass within the expected progenitor mass range. Furthermore, the yellow supergiant could be in a massive, interacting binary system, analogous to the possible yellow supergiant progenitor of the high-luminosity SN II-P 2004et. Finally, if the yellow supergiant is not the

  7. Systematic Effects of Progenitor Composition on Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Poludnenko, Alexei Y.; Gamezo, V. N.; Oran, E.

    2013-01-01

    Type Ia supernovae (SNIa) were first suggested over half a century ago to result from the thermonuclear incineration of a degenerate white dwarf star (WD) in a binary stellar system. In the past two decades, SNIa have emerged as a preeminent tool in cosmology, to a great extent, due to the significant improvements in the accuracy of their calibration as standard candles. This accuracy, however, is not perfect and the remaining scatter in the inferred intrinsic brightness of SNIa confounds the detailed studies of dark energy and, more importantly, leaves open the possibility of the presence of unknown systematic effects. Here we investigate one potential source of such systematic effects, namely carbon-to-oxygen ratio (C/O) of the progenitor WD, in the context of the delayed detonation model. In this scenario, the explosion starts as a subsonic deflagration that later transitions to a supersonic detonation (deflagration-to-detonation transition, or DDT). The onset of DDT is controlled by the interaction of the thermonuclear flame with the turbulent flowfield that develops during the explosion. Here we show that microscopic properties of the laminar thermonuclear flame vary strongly with the C/O ratio. In particular, when the 12C mass fraction decreases from 0.5 to 0.2, the flame speed decreases by a factor of 8 at the density 10^8 g/cc and by a factor of ~100 at the density 10^7 g/cc. This drastic change in flame speed is accompanied by the qualitative change in flame structure. Furthermore, we couple these new results on the properties of laminar deflagrations with the model of the spontaneous DDT process recently demonstrated using ab initio 3D simulations (Poludnenko et al., PRL 107, 054501 (2011)). Based on this, we show that decrease in the C/O ratio will systematically lead to significantly higher densities at which DDT occurs and, thus, to systematically larger 56Ni yields. Finally, we discuss the implications of these results that provide a physical

  8. Constraining the progenitors of short gamma-ray bursts

    NASA Astrophysics Data System (ADS)

    Tunnicliffe, Rachel L.

    2014-01-01

    So far the progenitors of short γ-ray bursts (SGRBs) have proved elusive. Their presence within both old and young environments and their bias against starforming regions provide tantalising evidence of a neutron star binary or neutron star - black hole merger origin. Within this thesis we study an array of characteristics of the population of SGRBs focussing in particular on their host environments and afterglow properties in the optical and X-ray bands. In particular we consider a set of SGRBs with no detectable host galaxy to deep limits and no clear host in the field from probabilistic arguments. These GRBs either represent a population at high redshift or with high offsets from low redshift hosts. Comparing the offsets of these GRBs from their potential hosts with random positions on the sky we find they are somewhat closer than expected, suggesting these GRBs are more likely to have been kicked from relatively local hosts. We also consider the issue of classification, given suggestions that the often used two second duration divide for SGRBs may produce a sample with a high contamination from collapsar objects or potentially a suggested third class of intermediate objects. We look at a sample of optically-detected SGRBs below the nominal two second divide and go on to consider properties of a larger sample of GRBs comparing varying duration bins. From constructed optical lightcurves and SEDs, we constrain the presence of extinction, jet breaks, supernovae and kilonovae. Though there is a suggestion that such a sample would be 40% contaminated from collapsar objects we find, from supernova constraints combined with duration and spectral hardness fits from Bromberg et al. (2013) that only 22% of objects in our sample could have been collapsars. The optical constraints placed on a kilonova (an r-process transient associated with neutron star mergers), suggest this transient is fainter than has sometimes been predicted but is consistent when considering

  9. Human Breast Progenitor Cell Numbers Are Regulated by WNT and TBX3

    PubMed Central

    Arendt, Lisa M.; St. Laurent, Jessica; Wronski, Ania; Caballero, Silvia; Lyle, Stephen R.; Naber, Stephen P.; Kuperwasser, Charlotte

    2014-01-01

    Background Although human breast development is mediated by hormonal and non-hormonal means, the mechanisms that regulate breast progenitor cell activity remain to be clarified. This limited understanding of breast progenitor cells has been due in part to the lack of appropriate model systems to detect and characterize their properties. Methods To examine the effects of WNT signaling and TBX3 expression on progenitor activity in the breast, primary human mammary epithelial cells (MEC) were isolated from reduction mammoplasty tissues and transduced with lentivirus to overexpress WNT1 or TBX3 or reduce expression of their cognate receptors using shRNA. Changes in progenitor activity were quantified using characterized assays. We identified WNT family members expressed by cell populations within the epithelium and assessed alterations in expression of WNT family ligands by MECs in response to TBX3 overexpression and treatment with estrogen and progesterone. Results Growth of MECs on collagen gels resulted in the formation of distinct luminal acinar and basal ductal colonies. Overexpression of TBX3 in MECs resulted in increased ductal colonies, while shTBX3 expression diminished both colony types. Increased WNT1 expression led to enhanced acinar colony formation, shLRP6 decreased both types of colonies. Estrogen stimulated the formation of acinar colonies in control MEC, but not shLRP6 MEC. Formation of ductal colonies was enhanced in response to progesterone. However, while shLRP6 decreased MEC responsiveness to progesterone, shTBX3 expression did not alter this response. Conclusions We identified two phenotypically distinguishable lineage-committed progenitor cells that contribute to different structural elements and are regulated via hormonal and non-hormonal mechanisms. WNT signaling regulates both types of progenitor activity. Progesterone favors the expansion of ductal progenitor cells, while estrogen stimulates the expansion of acinar progenitor cells. Paracrine

  10. Estrogen regulates luminal progenitor cell differentiation through H19 gene expression

    PubMed Central

    Basak, Pratima; Chatterjee, Sumanta; Weger, Steven; Bruce, M Christine; Murphy, Leigh C; Raouf, Afshin

    2015-01-01

    Although the role of estrogen signaling in breast cancer development has been extensively studied, the mechanisms that regulate the indispensable role of estrogen in normal mammary gland development have not been well studied. Because of the unavailability of culture system to maintain estrogen-receptor-positive (ERα+) cells in vitro, the molecular mechanisms that regulate estrogen/ERα signaling in the normal human breast are unknown. In the present study, we examined the effects of estrogen signaling on ERα+ human luminal progenitors using a modified matrigel assay and found that estrogen signaling increased the expansion potential of these progenitors. Furthermore, we found that blocking ERα attenuated luminal progenitor expansion and decreased the luminal colony-forming potential of these progenitors. Additionally, blocking ERα decreased H19 expression in the luminal progenitors and led to the development of smaller luminal colonies. We further showed that knocking down the H19 gene in the luminal progenitors significantly decreased the colony-forming potential of the luminal progenitors, and this phenotype could not be rescued by the addition of estrogen. Lastly, we explored the clinical relevance of the estrogen–H19 signaling axis in breast tumors and found that ERα+ tumors exhibited a higher expression of H19 as compared with ERα− tumors and that H19 expression showed a positive correlation with ERα expression in those tumors. Taken together, the present results indicate that the estrogen–ERα–H19 signaling axis plays a role in regulating the proliferation and differentiation potentials of the normal luminal progenitors and that this signaling network may also be important in the development of ER+ breast cancer tumors. PMID:25944846

  11. Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators.

    PubMed

    O'Brien, Lori L; Guo, Qiuyu; Lee, YoungJin; Tran, Tracy; Benazet, Jean-Denis; Whitney, Peter H; Valouev, Anton; McMahon, Andrew P

    2016-02-15

    Nephron endowment is determined by the self-renewal and induction of a nephron progenitor pool established at the onset of kidney development. In the mouse, the related transcriptional regulators Six1 and Six2 play non-overlapping roles in nephron progenitors. Transient Six1 activity prefigures, and is essential for, active nephrogenesis. By contrast, Six2 maintains later progenitor self-renewal from the onset of nephrogenesis. We compared the regulatory actions of Six2 in mouse and human nephron progenitors by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Surprisingly, SIX1 was identified as a SIX2 target unique to the human nephron progenitors. Furthermore, RNA-seq and immunostaining revealed overlapping SIX1 and SIX2 activity in 16 week human fetal nephron progenitors. Comparative bioinformatic analysis of human SIX1 and SIX2 ChIP-seq showed each factor targeted a similar set of cis-regulatory modules binding an identical target recognition motif. In contrast to the mouse where Six2 binds its own enhancers but does not interact with DNA around Six1, both human SIX1 and SIX2 bind homologous SIX2 enhancers and putative enhancers positioned around SIX1. Transgenic analysis of a putative human SIX1 enhancer in the mouse revealed a transient, mouse-like, pre-nephrogenic, Six1 regulatory pattern. Together, these data demonstrate a divergence in SIX-factor regulation between mouse and human nephron progenitors. In the human, an auto/cross-regulatory loop drives continued SIX1 and SIX2 expression during active nephrogenesis. By contrast, the mouse establishes only an auto-regulatory Six2 loop. These data suggest differential SIX-factor regulation might have contributed to species differences in nephron progenitor programs such as the duration of nephrogenesis and the final nephron count. PMID:26884396

  12. Disk dwarf galaxy as the progenitor of the Andromeda giant stream

    NASA Astrophysics Data System (ADS)

    Kirihara, Takanobu; Miki, Yohei; Mori, Masao; Kawaguchi, Toshihiro

    2016-08-01

    We present a study of the morphology of a progenitor galaxy that has been disrupted and formed a giant southern stellar stream in the halo of Andromeda galaxy(M31). N-body simulations of a minor merger of M31 with a dwarf galaxy suggest that the progenitor's rotation plays an important role in the formation of an asymmetric surface brightness distribution of the stream.

  13. Disk minor merger as the progenitor of the Andromeda giant stream

    NASA Astrophysics Data System (ADS)

    Kirihara, Takanobu

    2015-08-01

    Recent works have performed N -body simulations of a galaxy collision to reproduce observed shape and kinematics of a giant stellar stream (GSS) and shell-like structures in the halo of Andromeda galaxy (M31). So far, the study of the detailed comparison between the results of merger simulations and the observational data, M31's potential, orbit of the progenitor, and mass of the progenitor have been well understood. However, the morphology of the progenitor satellite galaxy has not yet examined in detail.Our simple analysis of the stellar count maps of red giant branch stars in the halo of M31 reveals an asymmetric internal structure of the giant stellar stream that can not be reproduced by a merger of a spherical symmetric progenitor. To reproduce such characteristic structure and to investigate the morphology of the disrupted progenitor, we perform N -body simulations and systematic parameter surveys varying the thickness of the disk progenitor and initial inclination of its disk. Our result suggests that a rotating component of the progenitor is required to reproduce an asymmetric internal structure of the GSS. Using the parameter that reproduces the observed structures in detail, we discuss the evolution and relaxation of the dark matter component that initially associated with the progenitor.In addition, we focus on the GSS as a probe of the density profile of the dark matter halo of M31 because the GSS is a huge structure (over 120 kpc) and its spatial and velocity structure have been observed in detail. We perform N -body simulation runs of the galaxy merger varying the power-law index of the outer-density profile and the total mass of the CDM halo of M31. The result suggests that a power-law index that is steeper than the CDM prediction.

  14. Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage

    PubMed Central

    Yu, Yin; Zheng, Hongjun; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Objective To date, no approved clinical intervention successfully prevents the progressive degradation of injured articular cartilage that leads to osteoarthritis (OA). Stem/progenitor cell populations within tissues of diarthrodial joint have shown their therapeutic potential in treating OA. However, this potential has not been fully realized due in part to the heterogeneity of these subpopulations. Characterization of clonal populations derived from a single cell may help identify more homogenous stem/progenitor populations within articular cartilage. Moreover, chondrogenic potential of clonal populations from different zones could be further examined to elucidate their differential roles in maintaining articular cartilage homeostasis. Method We combined FACS (Fluorescence-activated cell sorting) and clonogenicity screening to identify stem/progenitor cells cloned from single cells. High-efficiency colony-forming cells (HCCs) were isolated, and evaluated for stem/progenitor cell characteristics. HCCs were also isolated from different zones of articular cartilage. Their function was compared by lineage-specific gene expression, and differentiation potential. Results A difference in colony-forming efficiency was observed in terms of colony sizes. HCCs were highly clonogenic and multipotent, and overexpressed stem/progenitor cell markers. Also, proliferation and migration associated genes were over-expressed in HCCs. HCCs showed zonal differences with deep HCCs more chondrogenic and osteogenic than superficial HCCs. Conclusion Our approach is a simple yet practical way to identify homogeneous stem/progenitor cell populations with clonal origin. The discovery of progenitor cells demonstrates the intrinsic self-repairing potential of articular cartilage. Differences in differentiation potential may represent the distinct roles of superficial and deep zone stem/progenitor cells in the maintenance of articular cartilage homeostasis. PMID:25038490

  15. Circulating Progenitor Cells and Vascular Dysfunction in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pizarro, Sandra; García-Lucio, Jéssica; Peinado, Víctor I.; Tura-Ceide, Olga; Díez, Marta; Blanco, Isabel; Sitges, Marta; Petriz, Jordi; Torralba, Yolanda; Marín, Pedro; Roca, Josep; Barberà, Joan Albert

    2014-01-01

    Background In chronic obstructive pulmonary disease (COPD), decreased progenitor cells and impairment of systemic vascular function have been suggested to confer higher cardiovascular risk. The origin of these changes and their relationship with alterations in the pulmonary circulation are unknown. Objectives To investigate whether changes in the number of circulating hematopoietic progenitor cells are associated with pulmonary hypertension or changes in endothelial function. Methods 62 COPD patients and 35 controls (18 non-smokers and 17 smokers) without cardiovascular risk factors other than cigarette smoking were studied. The number of circulating progenitors was measured as CD45+CD34+CD133+ labeled cells by flow cytometry. Endothelial function was assessed by flow-mediated dilation. Markers of inflammation and angiogenesis were also measured in all subjects. Results Compared with controls, the number of circulating progenitor cells was reduced in COPD patients. Progenitor cells did not differ between control smokers and non-smokers. COPD patients with pulmonary hypertension showed greater number of progenitor cells than those without pulmonary hypertension. Systemic endothelial function was worse in both control smokers and COPD patients. Interleukin-6, fibrinogen, high sensitivity C-reactive protein, vascular endothelial growth factor and tumor necrosis factor were increased in COPD. In COPD patients, the number of circulating progenitor cells was inversely related to the flow-mediated dilation of systemic arteries. Conclusions Pulmonary and systemic vascular impairment in COPD is associated with cigarette smoking but not with the reduced number of circulating hematopoietic progenitors. The latter appears to be a consequence of the disease itself not related to smoking habit. PMID:25171153

  16. Regulation of hematopoietic progenitors by estrogens as a basis for new antileukemic strategies

    PubMed Central

    Sánchez-Aguilera, Abel; Méndez-Ferrer, Simón

    2016-01-01

    We recently reported that estrogens regulate survival, proliferation, and self-renewal of hematopoietic stem cells and progenitors via estrogen receptor-α activation. Through its proapoptotic effect on malignant progenitors, tamoxifen treatment blocks the development of JAK2V617F-induced myeloproliferative neoplasms in mice and sensitizes MLL-AF9-induced leukemias to chemotherapy, without detrimental effects on normal hematopoiesis. PMID:27308525

  17. Lymphoid Gene Upregulation on Circulating Progenitors Participates in Their T-Lineage Commitment.

    PubMed

    Zepponi, Vanessa; Michaels Lopez, Victoria; Martinez-Cingolani, Carolina; Boudil, Amine; Pasqualetto, Valérie; Skhiri, Lamia; Gautreau, Laetitia; Legrand, Agnès; Megret, Jerome; Zavala, Flora; Ezine, Sophie

    2015-07-01

    Extrathymic T cell precursors can be detected in many tissues and represent an immediately competent population for rapid T cell reconstitution in the event of immunodeficiencies. Blood T cell progenitors have been detected, but their source in the bone marrow (BM) remains unclear. Prospective purification of BM-resident and circulating progenitors, together with RT-PCR single-cell analysis, was used to evaluate and compare multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). Molecular analysis of circulating progenitors in comparison with BM-resident progenitors revealed that CCR9(+) progenitors are more abundant in the blood than CCR7(+) progenitors. Second, although Flt3(-) CLPs are less common in the BM, they are abundant in the blood and have reduced Cd25(+)-expressing cells and downregulated c-Kit and IL-7Rα intensities. Third, in contrast, stage 3 MPP (MPP3) cells, the unique circulating MPP subset, have upregulated Il7r, Gata3, and Notch1 in comparison with BM-resident counterparts. Evaluation of the populations' respective abilities to generate splenic T cell precursors (Lin(-)Thy1.2(+)CD25(+)IL7Rα(+)) after grafting recipient nude mice revealed that MPP3 cells were the most effective subset (relative to CLPs). Although several lymphoid genes are expressed by MPP3 cells and Flt3(-) CLPs, the latter only give rise to B cells in the spleen, and Notch1 expression level is not modulated in the blood, as for MPP3 cells. We conclude that CLPs have reached the point where they cannot be a Notch1 target, a limiting condition on the path to T cell engagement. PMID:26026063

  18. Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation

    SciTech Connect

    von Melchner, H.; Metcalf, D.; Mandel, T.E.

    1980-11-01

    After lethal irradiation of C57BL mice followed by the injection of 10/sup 7/ marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 h after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.

  19. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker.

    PubMed

    Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

    2016-07-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes. PMID:27350339

  20. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

    PubMed Central

    Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

    2016-01-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes. PMID:27350339

  1. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

    SciTech Connect

    LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J

    2008-09-19

    In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

  2. Concise Review: Chemical Approaches for Modulating Lineage-Specific Stem Cells and Progenitors

    PubMed Central

    Xu, Tao; Zhang, Mingliang; Laurent, Timothy; Xie, Min

    2013-01-01

    Generation and manipulation of lineage-restricted stem and progenitor cells in vitro and/or in vivo are critical for the development of stem cell-based clinical therapeutics. Lineage-restricted stem and progenitor cells have many advantageous qualities, including being able to efficiently engraft and differentiate into desirable cell types in vivo after transplantation, and they are much less tumorigenic than pluripotent cells. Generation of lineage-restricted stem and progenitor cells can be achieved by directed differentiation from pluripotent stem cells or lineage conversion from easily obtained somatic cells. Small molecules can be very helpful in these processes since they offer several important benefits. For example, the risk of tumorigenesis is greatly reduced when small molecules are used to replace integrated transcription factors, which are widely used in cell fate conversion. Furthermore, small molecules are relatively easy to apply, optimize, and manufacture, and they can more readily be developed into conventional pharmaceuticals. Alternatively, small molecules can be used to expand or selectively control the differentiation of lineage-restricted stem and progenitor cells for desirable therapeutics purposes in vitro or in vivo. Here we summarize recent progress in the use of small molecules for the expansion and generation of desirable lineage-restricted stem and progenitor cells in vitro and for selectively controlling cell fate of lineage-restricted stem and progenitor cells in vivo, thereby facilitating stem cell-based clinical applications. PMID:23580542

  3. CD133 positive progenitor endothelial cell lines from human cord blood.

    PubMed

    Paprocka, Maria; Krawczenko, Agnieszka; Dus, Danuta; Kantor, Aneta; Carreau, Aude; Grillon, Catherine; Kieda, Claudine

    2011-08-01

    Endothelial progenitor cells (EPCs) modulate postnatal vascularization and contribute to vessel regeneration in adults. Stem cells and progenitor cells were found in umbilical cord blood, bone marrow, and mobilized peripheral blood cells, from where they were isolated and cultured. However, the yield of progenitor cells is usually not sufficient for clinical application and the quality of progenitor cells varies. The aim of the study was the immortalization of early progenitor cells with high proliferative potential, capable to differentiate to EPCs and, further, toward endothelial cells. Two cell lines, namely HEPC-CB.1 and HEPC-CB.2 (human endothelial progenitor cells-cord blood) were isolated. As assessed by specific antibody labeling and flow cytometric analysis, they express a panel of stem cell markers: CD133, CD13, CD271, CD90 and also endothelial cell markers: CD202b, CD309 (VEGFR2), CD146, CD105, and CD143 but they do not present markers of finally differentiated endothelial cells: CD31, vWf, nor CD45 which is a specific hematopoietic cell marker. Using the multiplex Cytometric Bead Assay, the simultaneous production of proangiogenic cytokines IL8, angiogenin, and VEGF was demonstrated in normoxia and was shown to be increased by hypoxia. Both cell lines, similarly as mature endothelial cells, underwent in vitro pre-angiogenic process, formed pseudovessel structures and present an accelerated angiogenesis in hypoxic conditions. To date, these are the first CD133 positive established cell lines from human cord blood cells. PMID:21710642

  4. HDAC3 is essential for DNA replication in hematopoietic progenitor cells

    PubMed Central

    Summers, Alyssa R.; Fischer, Melissa A.; Stengel, Kristy R.; Zhao, Yue; Kaiser, Jonathan F.; Wells, Christina E.; Hunt, Aubrey; Bhaskara, Srividya; Luzwick, Jessica W.; Sampathi, Shilpa; Chen, Xi; Thompson, Mary Ann; Cortez, David; Hiebert, Scott W.

    2013-01-01

    Histone deacetylase 3 (HDAC3) contributes to the regulation of gene expression, chromatin structure, and genomic stability. Because HDAC3 associates with oncoproteins that drive leukemia and lymphoma, we engineered a conditional deletion allele in mice to explore the physiological roles of Hdac3 in hematopoiesis. We used the Vav-Cre transgenic allele to trigger recombination, which yielded a dramatic loss of lymphoid cells, hypocellular bone marrow, and mild anemia. Phenotypic and functional analysis suggested that Hdac3 was required for the formation of the earliest lymphoid progenitor cells in the marrow, but that the marrow contained 3–5 times more multipotent progenitor cells. Hdac3–/– stem cells were severely compromised in competitive bone marrow transplantation. In vitro, Hdac3–/– stem and progenitor cells failed to proliferate, and most cells remained undifferentiated. Moreover, one-third of the Hdac3–/– stem and progenitor cells were in S phase 2 hours after BrdU labeling in vivo, suggesting that these cells were impaired in transit through the S phase. DNA fiber-labeling experiments indicated that Hdac3 was required for efficient DNA replication in hematopoietic stem and progenitor cells. Thus, Hdac3 is required for the passage of hematopoietic stem/progenitor cells through the S phase, for stem cell functions, and for lymphopoiesis. PMID:23921131

  5. Progenitor Cell Mobilization by Gamma-tocotrienol: A Promising Radiation Countermeasure

    PubMed Central

    Singh, Vijay K.; Fatanmi, Oluseyi O.; Verma, Amit; Newman, Victoria L.; Wise, Stephen Y.; Romaine, Patricia L.P.; Berg, Allison N.

    2016-01-01

    Abstract This article reviews studies of progenitor mobilization with gamma-tocotrienol (GT3), a tocol under advanced development as a radiation countermeasure for acute radiation syndrome (ARS). GT3 protects mice against high doses of ionizing radiation and induces high levels of granulocyte colony-stimulating factor (G-CSF). GT3‐induced G-CSF in conjunction with AMD3100 (a chemokine receptor antagonist clinically used to improve the yield of mobilized progenitors) mobilizes progenitors; these mobilized progenitors mitigate injury when infused to mice exposed to acute, high-dose ionizing radiation. The administration of a G-CSF antibody to GT3‐injected donor mice abrogated the radiomitigative efficacy of blood or peripheral blood mononuclear cells (PBMC) in irradiated recipient mice. The efficacy of GT3‐injected donor mice blood or PBMC was comparable to a recently published article involving blood or mononuclear cells obtained from mice injected with G-CSF. The injected progenitors were found to localize in various tissues of irradiated hosts. The authors demonstrate the efficacy of a bridging therapy in a preclinical animal model that allows the lymphohematopoietic system of severely immunocompromised mice to recover. This suggests that GT3 is a highly effective agent for radioprotection and mobilizing progenitors with significant therapeutic potential. Therefore, GT3 may be considered for further translational development and ultimately for use in humans. PMID:27356050

  6. Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors

    PubMed Central

    Henry, Curtis J.; Casás-Selves, Matias; Kim, Jihye; Zaberezhnyy, Vadym; Aghili, Leila; Daniel, Ashley E.; Jimenez, Linda; Azam, Tania; McNamee, Eoin N.; Clambey, Eric T.; Klawitter, Jelena; Serkova, Natalie J.; Tan, Aik Choon; Dinarello, Charles A.; DeGregori, James

    2015-01-01

    The incidence of cancer is higher in the elderly; however, many of the underlying mechanisms for this association remain unexplored. Here, we have shown that B cell progenitors in old mice exhibit marked signaling, gene expression, and metabolic defects. Moreover, B cell progenitors that developed from hematopoietic stem cells (HSCs) transferred from young mice into aged animals exhibited similar fitness defects. We further demonstrated that ectopic expression of the oncogenes BCR-ABL, NRASV12, or Myc restored B cell progenitor fitness, leading to selection for oncogenically initiated cells and leukemogenesis specifically in the context of an aged hematopoietic system. Aging was associated with increased inflammation in the BM microenvironment, and induction of inflammation in young mice phenocopied aging-associated B lymphopoiesis. Conversely, a reduction of inflammation in aged mice via transgenic expression of α-1-antitrypsin or IL-37 preserved the function of B cell progenitors and prevented NRASV12-mediated oncogenesis. We conclude that chronic inflammatory microenvironments in old age lead to reductions in the fitness of B cell progenitor populations. This reduced progenitor pool fitness engenders selection for cells harboring oncogenic mutations, in part due to their ability to correct aging-associated functional defects. Thus, modulation of inflammation — a common feature of aging — has the potential to limit aging-associated oncogenesis. PMID:26551682

  7. Stellar Forensics III: A post-explosion view of the progenitors of core-collapse supernovae

    NASA Astrophysics Data System (ADS)

    Maund, Justyn

    2011-10-01

    Recent studies have used high spatial resolution HST observations of supernova {SN} sites to directly identify the progenitors of core-collapse SNe on pre-explosion images. These studies have set constraints about the nature of massive stars and their evolution just prior to their explosion as SNe. Now, at late-times when the SNe have faded sufficiently, it is possible to return to the sites of these core-collapse SNe to search for clues about the nature of their progenitors.We request time to conduct deep, late-time, high-resolution imaging with ACS/WFC of the sites of two core-collapse SNe 2009kr and 2009md. We aim to: 1} Confirm our original identifications, made in pre-explosion images, by confirming that the progenitors are now missing; 2} Apply image subtraction techniques for this late-time imaging with our pre-explosion images to determine accurate photometry of the progenitors to constrain their temperatures and luminosities; and 3} study the stellar populations in the immediate vicinities of these SNe, previously obscured by the progenitor and the SN, to provide a measure of the progenitor's age, as well. HST provides the unique combination of high-resolution optical/IR imaging at very faint magnitudes that will facilitate this study.

  8. The Final Word on the Progenitor of the Type II-Plateau Supernova SN 2006ov

    NASA Astrophysics Data System (ADS)

    Leonard, Douglas

    2011-10-01

    Despite recent rapid progress, the field of supernova {SN} progenitor identification remains in its infancy, with only five supernovae having had unambiguous detection and characterization of their progenitor stars made. The existence of deep pre-SN WFPC2 images of the site of the nearby core-collapse {Type II-Plateau} SN 2006ov has enabled two independent searches for its progenitor star to be carried out. While both studies agree that an object is located at the location of SN 2006ov in the pre-SN images, they disagree on whether the light from this source {or, part of it} is, in fact, coming from the actual progenitor star. The time is ripe to settle the issue: A single-orbit reobservation of the SN site with HST/ACS will permit the definitive determination of whether this object is indeed associated with SN 2006ov. If it is, and its flux is found to have diminished {it was an extended source} or vanished {it was an isolated star}, then this will enable the third conclusive characterization of a Type II-Plateau supernova's progenitor star's properties to be made. If it is not, then a firm upper mass limit on the progenitor star will be confidently declared the final word on the topic.

  9. Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries.

    PubMed

    Wongtrakoongate, Patompon

    2015-01-26

    Recent advances in stem cell biology have shed light on how normal stem and progenitor cells can evolve to acquire malignant characteristics during tumorigenesis. The cancer counterparts of normal stem and progenitor cells might be occurred through alterations of stem cell fates including an increase in self-renewal capability and a decrease in differentiation and/or apoptosis. This oncogenic evolution of cancer stem and progenitor cells, which often associates with aggressive phenotypes of the tumorigenic cells, is controlled in part by dysregulated epigenetic mechanisms including aberrant DNA methylation leading to abnormal epigenetic memory. Epigenetic therapy by targeting DNA methyltransferases (DNMT) 1, DNMT3A and DNMT3B via 5-Azacytidine (Aza) and 5-Aza-2'-deoxycytidine (Aza-dC) has proved to be successful toward treatment of hematologic neoplasms especially for patients with myelodysplastic syndrome. In this review, I summarize the current knowledge of mechanisms underlying the inhibition of DNA methylation by Aza and Aza-dC, and of their apoptotic- and differentiation-inducing effects on cancer stem and progenitor cells in leukemia, medulloblastoma, glioblastoma, neuroblastoma, prostate cancer, pancreatic cancer and testicular germ cell tumors. Since cancer stem and progenitor cells are implicated in cancer aggressiveness such as tumor formation, progression, metastasis and recurrence, I propose that effective therapeutic strategies might be achieved through eradication of cancer stem and progenitor cells by targeting the DNA methylation machineries to interfere their "malignant memory". PMID:25621113

  10. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals

    PubMed Central

    Toda, Tomohisa; Shinmyo, Yohei; Dinh Duong, Tung Anh; Masuda, Kosuke; Kawasaki, Hiroshi

    2016-01-01

    Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID:27403992

  11. In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors.

    PubMed

    Richie Ehrlich, Lauren I; Serwold, Thomas; Weissman, Irving L

    2011-03-01

    The identity of T-cell progenitors that seed the thymus has remained controversial, largely because many studies differ over whether these progenitors retain myeloid potential. Contradictory reports diverge in their use of various in vitro and in vivo assays. To consolidate these discordant findings, we compared the myeloid potential of 2 putative thymus seeding populations, common lymphoid progenitors (CLPs) and multipotent progenitors (MPPs), and the earliest intrathymic progenitor (DN1), using 2 in vitro assays and in vivo readouts. These assays gave contradictory results: CLP and DN1 displayed surprisingly robust myeloid potential on OP9-DL1 in vitro stromal cocultures but displayed little myeloid potential in vivo, as well as in methylcellulose cultures. MPP, on the other hand, displayed robust myeloid potential in all settings. We conclude that stromal cocultures reveal cryptic, but nonphysiologic, myeloid potentials of lymphoid progenitors, providing an explanation for contradictory findings in the field and underscoring the importance of using in vivo assays for the determination of physiologic lineage potentials. PMID:21163922

  12. Collision Tomography: Physical Properties of Possible Progenitors of the Andromeda Stellar Stream

    NASA Astrophysics Data System (ADS)

    Miki, Yohei; Mori, Masao; Rich, R. Michael

    2016-08-01

    To unveil a progenitor of the Andromeda Giant Stellar Stream, we investigate the interaction between an accreting satellite galaxy and the Andromeda Galaxy using an N-body simulation. We perform a comprehensive exploration of the properties of the progenitor dwarf galaxy, using 247 models of varying mass, mass distribution, and size. We show that the binding energy of the progenitor is the crucial parameter in reproducing the Andromeda Giant Stellar Stream and the shell-like structures surrounding the Andromeda Galaxy. As a result of the simulations, the progenitor must satisfy a simple scaling relation between the core radius, the total mass and the tidal radius. Using this relation, we successfully constrain the physical properties of the progenitors to have masses ranging from 5× {10}8{M}ȯ to 5× {10}9{M}ȯ and central surface densities around {10}3 {M}ȯ {{pc}}-2. A detailed comparison between our result and the nearby observed galaxies indicates that possible progenitors of the Andromeda Giant Stellar Stream include a dwarf elliptical galaxy, a dwarf irregular galaxy, and a small spiral galaxy.

  13. Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors.

    PubMed

    Wölfler, Albert; Danen-van Oorschot, Astrid A; Haanstra, Jurgen R; Valkhof, Marijke; Bodner, Claudia; Vroegindeweij, Eric; van Strien, Paulette; Novak, Alexandra; Cupedo, Tom; Touw, Ivo P

    2010-11-18

    Hematopoiesis is tightly controlled by transcription regulatory networks, but how and when specific transcription factors control lineage commitment are still largely unknown. Within the hematopoietic stem cell (Lin(-)Sca-1(+)c-Kit(+)) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. CCAAT/enhancer binding protein α (C/EBPα) represents one of these factors and is involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor cells, which express C/EBPα, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP(+) cells represent a significant subset of multipotent hematopoietic progenitors, which predominantly give rise to myeloid cells in steady-state hematopoiesis. C/EBPα induced a strong myeloid gene expression signature and down-regulated E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP(+) cells compose a fraction of early thymic progenitors with robust myeloid potential. However, Cebpa/EYFP(+) multipotent hematopoietic progenitors and early thymic progenitors retained the ability to develop into erythroid and T-lymphoid lineages, respectively. These findings support an instructive but argue against a lineage-restrictive role of C/EBPα in multipotent hematopoietic and thymic progenitors. PMID:20807890

  14. Dysregulation of Vascular Endothelial Progenitor Cells Lung-Homing in Subjects with COPD

    PubMed Central

    Salter, Brittany M.; Manzoor, Fizza; Beaudin, Suzanne; Kjarsgaard, Melanie; Nair, Parameswaran; Gauvreau, Gail M.; Sehmi, Roma

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow limitation and progressive decline of lung function and punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating mobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular endothelial progenitor cells (VEPCs) are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex-smokers with diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted primitive hemopoietic progenitors (HPCs) and VEPC were enumerated by flow cytometry. Migration and adhesive responses to fibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood, VEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups in either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal cell-derived factor-1alpha (SDF-1α) compared to normal controls. This was associated with greater numbers of CXCR4+ progenitors in sputum from COPD. Increased migrational responsiveness of progenitor cells may promote lung-homing of VEPC in COPD which may disrupt maintenance and repair of the airways and contribute to COPD disease pathogenesis. PMID:27445517

  15. Selection of Phage Display Peptides Targeting Human Pluripotent Stem Cell-Derived Progenitor Cell Lines.

    PubMed

    Bignone, Paola A; Krupa, Rachel A; West, Michael D; Larocca, David

    2016-01-01

    The ability of human pluripotent stem cells (hPS) to both self-renew and differentiate into virtually any cell type makes them a promising source of cells for cell-based regenerative therapies. However, stem cell identity, purity, and scalability remain formidable challenges that need to be overcome for translation of pluripotent stem cell research into clinical applications. Directed differentiation from hPS cells is inefficient and residual contamination with pluripotent cells that have the potential to form tumors remains problematic. The derivation of scalable (self-renewing) embryonic progenitor stem cell lines offers a solution because they are well defined and clonally pure. Clonally pure progenitor stem cell lines also provide a means for identifying cell surface targeting reagents that are useful for identification, tracking, and repeated derivation of the corresponding progenitor stem cell types from additional hPS cell sources. Such stem cell targeting reagents can then be applied to the manufacture of genetically diverse banks of human embryonic progenitor cell lines for drug screening, disease modeling, and cell therapy. Here we present methods to identify human embryonic progenitor stem cell targeting peptides by selection of phage display libraries on clonal embryonic progenitor cell lines and demonstrate their use for targeting quantum dots (Qdots) for stem cell labeling. PMID:25410289

  16. Distribution and Characterization of Progenitor Cells within the Human Filum Terminale

    PubMed Central

    Jaff, Nasren; Ossoinak, Amina; Jansson, Katarina; Hägerstrand, Anders; Johansson, Clas B.; Brundin, Lou; Svensson, Mikael

    2011-01-01

    Background Filum terminale (FT) is a structure that is intimately associated with conus medullaris, the most caudal part of the spinal cord. It is well documented that certain regions of the adult human central nervous system contains undifferentiated, progenitor cells or multipotent precursors. The primary objective of this study was to describe the distribution and progenitor features of this cell population in humans, and to confirm their ability to differentiate within the neuroectodermal lineage. Methodology/Principal Findings We demonstrate that neural stem/progenitor cells are present in FT obtained from patients treated for tethered cord. When human or rat FT-derived cells were cultured in defined medium, they proliferated and formed neurospheres in 13 out of 21 individuals. Cells expressing Sox2 and Musashi-1 were found to outline the central canal, and also to be distributed in islets throughout the whole FT. Following plating, the cells developed antigen profiles characteristic of astrocytes (GFAP) and neurons (β-III-tubulin). Addition of PDGF-BB directed the cells towards a neuronal fate. Moreover, the cells obtained from young donors shows higher capacity for proliferation and are easier to expand than cells derived from older donors. Conclusion/Significance The identification of bona fide neural progenitor cells in FT suggests a possible role for progenitor cells in this extension of conus medullaris and may provide an additional source of such cells for possible therapeutic purposes. Filum terminale, human, progenitor cells, neuron, astrocytes, spinal cord. PMID:22096566

  17. Progenitor Cell Mobilization by Gamma-tocotrienol: A Promising Radiation Countermeasure.

    PubMed

    Singh, Vijay K; Fatanmi, Oluseyi O; Verma, Amit; Newman, Victoria L; Wise, Stephen Y; Romaine, Patricia L P; Berg, Allison N

    2016-08-01

    This article reviews studies of progenitor mobilization with gamma-tocotrienol (GT3), a tocol under advanced development as a radiation countermeasure for acute radiation syndrome (ARS). GT3 protects mice against high doses of ionizing radiation and induces high levels of granulocyte colony-stimulating factor (G-CSF). GT3-induced G-CSF in conjunction with AMD3100 (a chemokine receptor antagonist clinically used to improve the yield of mobilized progenitors) mobilizes progenitors; these mobilized progenitors mitigate injury when infused to mice exposed to acute, high-dose ionizing radiation. The administration of a G-CSF antibody to GT3-injected donor mice abrogated the radiomitigative efficacy of blood or peripheral blood mononuclear cells (PBMC) in irradiated recipient mice. The efficacy of GT3-injected donor mice blood or PBMC was comparable to a recently published article involving blood or mononuclear cells obtained from mice injected with G-CSF. The injected progenitors were found to localize in various tissues of irradiated hosts. The authors demonstrate the efficacy of a bridging therapy in a preclinical animal model that allows the lymphohematopoietic system of severely immunocompromised mice to recover. This suggests that GT3 is a highly effective agent for radioprotection and mobilizing progenitors with significant therapeutic potential. Therefore, GT3 may be considered for further translational development and ultimately for use in humans. PMID:27356050

  18. DISCRIMINATING THE PROGENITOR TYPE OF SUPERNOVA REMNANTS WITH IRON K-SHELL EMISSION

    SciTech Connect

    Yamaguchi, Hiroya; Petre, Robert; Enoto, Teruaki; Badenes, Carles; Nakano, Toshio; Hiraga, Junko S.; Castro, Daniel; Hughes, John P.; Maeda, Yoshitomo; Nobukawa, Masayoshi; Uchida, Hiroyuki; Safi-Harb, Samar; Slane, Patrick O.; Smith, Randall K.

    2014-04-20

    Supernova remnants (SNRs) retain crucial information about both their parent explosion and circumstellar material left behind by their progenitor. However, the complexity of the interaction between supernova ejecta and ambient medium often blurs this information, and it is not uncommon for the basic progenitor type (Ia or core-collapse) of well-studied remnants to remain uncertain. Here we present a powerful new observational diagnostic to discriminate between progenitor types and constrain the ambient medium density of SNRs using solely Fe K-shell X-ray emission. We analyze all extant Suzaku observations of SNRs and detect Fe Kα emission from 23 young or middle-aged remnants, including five first detections (IC 443, G292.0+1.8, G337.2-0.7, N49, and N63A). The Fe Kα centroids clearly separate progenitor types, with the Fe-rich ejecta in Type Ia remnants being significantly less ionized than in core-collapse SNRs. Within each progenitor group, the Fe Kα luminosity and centroid are well correlated, with more luminous objects having more highly ionized Fe. Our results indicate that there is a strong connection between explosion type and ambient medium density, and suggest that Type Ia supernova progenitors do not substantially modify their surroundings at radii of up to several parsecs. We also detect a K-shell radiative recombination continuum of Fe in W49B and IC 443, implying a strong circumstellar interaction in the early evolutionary phases of these core-collapse remnants.

  19. The progenitor cell compartment in the feline liver: an (immuno)histochemical investigation.

    PubMed

    Ijzer, J; Kisjes, J R; Penning, L C; Rothuizen, J; van den Ingh, T S G A M

    2009-07-01

    The hepatic progenitor compartment is of vital importance in liver regeneration when hepatocellular replication is impaired, as it occurs in acute fulminant hepatitis or severe liver fibrosis. It consists of resident progenitor cells in the normal liver, and ductular reaction and intermediate hepatobiliary cells in diseased livers. An histologic and immunohistochemical study was conducted to demonstrate putative hepatic progenitor cells in the normal liver (n = 5) and in a range of hepatic diseases (n = 13) in the cat. Formalin-fixed, paraffin-embedded specimens were stained with HE, the van Gieson stain, and the reticulin stain according to Gordon and Sweet, and immunohistochemically stained for cytokeratin-7 (CK7), human hepatocyte marker 1 (Hepar1), and multidrug resistance-binding protein-2/ATP binding cassette C2 (MRP2). The normal feline liver contains a liver progenitor cell morphologically similar to humans and dogs, which resides in the canal of Hering. In acute and chronic feline liver diseases a ductular reaction is present, whether in the parenchyma or in a portal or septal location. The putative progenitor cells could easily be demonstrated by staining for CK7, whereas they were generally negative for Hepar1 and MRP2. In a parenchymal ductular reaction mitotic figures and cells with an intermediate hepatobiliary phenotype could be demonstrated. This is the first account of hepatic progenitor cells in feline liver. PMID:19329493

  20. Position-dependent plasticity of distinct progenitor types in the primitive streak

    PubMed Central

    Wymeersch, Filip J; Huang, Yali; Blin, Guillaume; Cambray, Noemí; Wilkie, Ron; Wong, Frederick CK; Wilson, Valerie

    2016-01-01

    The rostrocaudal (head-to-tail) axis is supplied by populations of progenitors at the caudal end of the embryo. Despite recent advances characterising one of these populations, the neuromesodermal progenitors, their nature and relationship to other populations remains unclear. Here we show that neuromesodermal progenitors are a single Sox2lowTlow entity whose choice of neural or mesodermal fate is dictated by their position in the progenitor region. The choice of mesoderm fate is Wnt/β-catenin dependent. Wnt/β-catenin signalling is also required for a previously unrecognised phase of progenitor expansion during mid-trunk formation. Lateral/ventral mesoderm progenitors represent a distinct committed state that is unable to differentiate to neural fates, even upon overexpression of the neural transcription factor Sox2. They do not require Wnt/β-catenin signalling for mesoderm differentiation. This information aids the correct interpretation of in vivo genetic studies and the development of in vitro protocols for generating physiologically-relevant cell populations of clinical interest. DOI: http://dx.doi.org/10.7554/eLife.10042.001 PMID:26780186

  1. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals.

    PubMed

    Toda, Tomohisa; Shinmyo, Yohei; Dinh Duong, Tung Anh; Masuda, Kosuke; Kawasaki, Hiroshi

    2016-01-01

    Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID:27403992

  2. Position-dependent plasticity of distinct progenitor types in the primitive streak.

    PubMed

    Wymeersch, Filip J; Huang, Yali; Blin, Guillaume; Cambray, Noemí; Wilkie, Ron; Wong, Frederick Ck; Wilson, Valerie

    2016-01-01

    The rostrocaudal (head-to-tail) axis is supplied by populations of progenitors at the caudal end of the embryo. Despite recent advances characterising one of these populations, the neuromesodermal progenitors, their nature and relationship to other populations remains unclear. Here we show that neuromesodermal progenitors are a single Sox2(low)T(low) entity whose choice of neural or mesodermal fate is dictated by their position in the progenitor region. The choice of mesoderm fate is Wnt/β-catenin dependent. Wnt/β-catenin signalling is also required for a previously unrecognised phase of progenitor expansion during mid-trunk formation. Lateral/ventral mesoderm progenitors represent a distinct committed state that is unable to differentiate to neural fates, even upon overexpression of the neural transcription factor Sox2. They do not require Wnt/β-catenin signalling for mesoderm differentiation. This information aids the correct interpretation of in vivo genetic studies and the development of in vitro protocols for generating physiologically-relevant cell populations of clinical interest. PMID:26780186

  3. Anti‐Inflammatory Peptides From Cardiac Progenitors Ameliorate Dysfunction After Myocardial Infarction

    PubMed Central

    Liu, Mei‐Lan; Nagai, Toshio; Tokunaga, Masakuni; Iwanaga, Koji; Matsuura, Katsuhisa; Takahashi, Toshinao; Kanda, Masato; Kondo, Naomichi; Naito, Atsuhiko T.; Komuro, Issei; Kobayashi, Yoshio

    2014-01-01

    Background Cardiac cell therapy has been proposed as one of the new strategies against myocardial infarction. Although several reports showed improvement of the function of ischemic heart, the effects of cell therapy vary among the studies and the mechanisms of the beneficial effects are still unknown. Previously, we reported that clonal stem cell antigen‐1–positive cardiac progenitor cells exerted a therapeutic effect when transplanted into the ischemic heart. Our aims were to identify the cardiac progenitor‐specific paracrine factor and to elucidate the mechanism of its beneficial effect. Methods and Results By using an antibody array, we found that soluble junctional adhesion molecule‐A (JAM‐A) was abundantly secreted from cardiac progenitor cells. Pretreatment of neutrophils with conditioned medium from cultured cardiac progenitor cells or soluble JAM‐A inhibited transendothelial migration and reduced motility of neutrophils. These inhibitory effects were attenuated by anti–JAM‐A neutralizing antibody. Injection of cardiac progenitor cells into infarct heart attenuated neutrophil infiltration and expression of inflammatory cytokines. Injection of soluble JAM‐A–expressing, but not of JAM‐A siRNA–expressing, cardiac progenitor cells into the infarct heart prevented cardiac remodeling and reduced fibrosis area. Conclusions Soluble JAM‐A secreted from cardiac progenitor cells reduces infiltration of neutrophils after myocardial infarction and ameliorates tissue damage through prevention of excess inflammation. Our finding may lead to a new therapy for cardiovascular disease by using the anti‐inflammatory effect of JAM‐A. PMID:25468657

  4. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    SciTech Connect

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas . E-mail: andreas.hecht@mol-med.uni-freiburg.de

    2007-02-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of {beta}-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/{beta}-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity.

  5. Myelination in vitro of rodent dorsal root ganglia by glial progenitor cells.

    PubMed

    Zajicek, J; Compston, A

    1994-12-01

    Oligodendrocytes synthesize myelin in the mammalian central nervous system; they develop from glial progenitors which, at least in vitro, are bipotential and also differentiate into astrocytes. Maturation of these O-2A progenitors is known to be influenced by growth factors and by extracellular matrix molecules. We investigated the effect of neurons on glial development by co-culturing highly purified rodent embryonic dorsal root ganglia with neonatal O-2A progenitors. Neurons produce signals, including platelet-derived growth factor BB and basic fibroblast growth factor, which stimulate progenitor cells to synthesize DNA; axonal contact is associated with down-regulation in the expression of complex ganglioside surface molecules on O-2A progenitors; with maturation, many of these cells develop into oligodendrocytes allowing the normal process of myelination to take place, but neurons also promote the differentiation of type 2 astrocytes. This orchestration of proliferation and differentiation in O-2A progenitor cells favours the development of glial-neuronal interactions needed for saltatory conduction of the nerve impulse. PMID:7820570

  6. Oligodendrocyte progenitor programming and reprogramming: Toward myelin regeneration.

    PubMed

    Lopez Juarez, Alejandro; He, Danyang; Richard Lu, Q

    2016-05-01

    Demyelinating diseases such as multiple sclerosis (MS) are among the most disabling and cost-intensive neurological disorders. The loss of myelin in the central nervous system, produced by oligodendrocytes (OLs), impairs saltatory nerve conduction, leading to motor and cognitive deficits. Immunosuppression therapy has a limited efficacy in MS patients, arguing for a paradigm shift to strategies that target OL lineage cells to achieve myelin repair. The inhibitory microenvironment in MS lesions abrogates the expansion and differentiation of resident OL precursor cells (OPCs) into mature myelin-forming OLs. Recent studies indicate that OPCs display a highly plastic ability to differentiate into alternative cell lineages under certain circumstances. Thus, understanding the mechanisms that maintain and control OPC fate and differentiation into mature OLs in a hostile, non-permissive lesion environment may open new opportunities for regenerative therapies. In this review, we will focus on 1) the plasticity of OPCs in terms of their developmental origins, distribution, and differentiation potentials in the normal and injured brain; 2) recent discoveries of extrinsic and intrinsic factors and small molecule compounds that control OPC specification and differentiation; and 3) therapeutic potential for motivation of neural progenitor cells and reprogramming of differentiated cells into OPCs and their likely impacts on remyelination. OL-based therapies through activating regenerative potentials of OPCs or cell replacement offer exciting opportunities for innovative strategies to promote remyelination and neuroprotection in devastating demyelinating diseases like MS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). PMID:26546966

  7. Connective tissue progenitor cell growth characteristics on textured substrates.

    PubMed

    Mata, Alvaro; Boehm, Cynthia; Fleischman, Aaron J; Muschler, George F; Roy, Shuvo

    2007-01-01

    Growth characteristics of human connective tissue progenitor (CTP) cells were investigated on smooth and textured substrates, which were produced using MEMS (microelectromechanical systems) fabrication technology. Human bone marrow derived cells were cultured for 9 days under conditions promoting osteoblastic differentiation on polydimethylsiloxane (PDMS) substrates comprising smooth (non-patterned) surfaces (SMOOTH), 4 different cylindrical post micro-textures (POSTS) that were 7-10 microm high and 5, 10, 20, and 40 microm diameter, respectively, and channel micro-textures (CHANNELS) with curved cross-sections that were 11 microm high, 45 microm wide, and separated by 5 microm wide ridges. Standard glass-tissue culture surfaces were used as controls. Micro-textures resulted in the modification of CTP morphology, attachment, migration, and proliferation characteristics. Specifically, cells on POSTS exhibited more contoured morphology with closely packed cytoskeletal actin microfilaments compared to the more random orientation in cells grown on SMOOTH. CTP colonies on 10 gm-diameter POSTS exhibited higher cell number than any other POSTS, and a significant increase in cell number (442%) compared to colonies on SMOOTH (71%). On CHANNELS, colonies tended to be denser (229%) than on POSTS (up to 140% on 10 microm POSTS), and significantly more so compared to those on SMOOTH (104%). PMID:18019838

  8. Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage.

    PubMed

    Schminke, Boris; Trautmann, Sandra; Mai, Burkhard; Miosge, Nicolai; Blaschke, Sabine

    2016-02-01

    Mesenchymal stem cells are known to exert immunomodulatory effects in inflammatory diseases. Immuneregulatory cells lead to progressive joint destruction in rheumatoid arthritis (RA). Proinflammatory cytokines, such as tumour necrosis factor α (TNF-α) and interleukins (ILs) are the main players. Here, we studied progenitor cells from RA cartilage (RA-CPCs) that are positive for IL-17 receptors to determinate the effects of inflammation on their chondrogenic potenial. IL-17A/F reduced the chondrogenic potential of these cells via the upregulation of RUNX2 protein and enhanced IL-6 protein and MMP3 mRNA levels. Blocking antibodies against IL-17 positively influenced their repair potential. Furthermore, treating the RA-CPCs with the anti-human IL-17 antibody secukinumab or the anti-TNF-α antibody adalimumab reduced the proinflammatory IL-6 protein level and positively influenced the secretion of anti-inflammatory IL-10 protein. Additionally, adalimumab and secukinumab in particular reduced RUNX2 protein to promote chondrogenesis. The amelioration of inflammation, particularly via IL-17 antagonism, might be a new therapeutic approach for enhancing intrinsic cartilage repair mechanisms in RA patients. PMID:26558442

  9. L-arginine is a radioprotector for hematopoietic progenitor cells.

    PubMed

    Pearce, Linda L; Zheng, Xichen; Martinez-Bosch, Sandra; Kerr, Patrick P; Khlangwiset, Pornsri; Epperly, Michael W; Fink, Mitchell P; Greenberger, Joel S; Peterson, Jim

    2012-06-01

    L-arginine is shown to protect hematopoietic progenitor (32D cl 3) cells from death due to exposure to γ radiation ((137)Cs). Some of the other intermediates in the urea cycle, namely ornithine and citrulline, plus urea itself, were not found to have any significant impact on cell survival after irradiation. Intriguingly, supplementation of irradiated cells with L-arginine results in decreased production of peroxynitrite, suggesting that suppression of superoxide generation by nitric oxide synthase in one or more microenvironments is an important factor in the observed radioprotection. The absence of any radioprotective effect of L-arginine in cells at 3% oxygen also confirms the involvement of one or more oxygen-derived species. Knockdown experiments with nitric oxide synthase (NOS) siRNAs in cells and NOS knockout animals confirm that the observed radioprotection is associated with nNOS (NOS-1). L-arginine also ameliorates the transient inhibition of the electron-transport chain complex I that occurs within 30 min of completing the dose (10 Gy) and that appears to be a functional marker for postirradiation mitochondrial oxidant production. PMID:22175298

  10. On the Afterglow and Progenitor of FRB 150418

    NASA Astrophysics Data System (ADS)

    Zhang, Bing

    2016-05-01

    Keane et al. recently detected a fading radio source following FRB 150418, leading to the identification of a putative host galaxy at z = 0.492 ± 0.008. Assuming that the fading source is the afterglow of FRB 150418, I model the afterglow and constrain the isotropic energy of the explosion to be a few 1050 erg, comparable to that of a short-duration gamma-ray burst (GRB). The outflow may have a jet opening angle of ∼0.22 rad, so that the beaming-corrected energy is below 1049 erg. The results rule out most fast radio burst (FRB) progenitor models for this FRB, but may be consistent with either of the following two scenarios. The first scenario invokes a merger of an NS–NS binary, which produced an undetected short GRB and a supra-massive neutron star, which subsequently collapsed into a black hole, probably hundreds of seconds after the short GRB. The second scenario invokes a merger of a compact star binary (BH–BH, NS–NS, or BH–NS) system whose pre-merger dynamical magnetospheric activities made the FRB, which is followed by an undetected short GRB-like transient. The gravitational-wave (GW) event GW 150914 would be a sister of FRB 150418 in this second scenario. In both cases, one expects an exciting prospect of GW/FRB/GRB associations.

  11. Transdifferentiation of human endothelial progenitors into smooth muscle cells.

    PubMed

    Ji, HaYeun; Atchison, Leigh; Chen, Zaozao; Chakraborty, Syandan; Jung, Youngmee; Truskey, George A; Christoforou, Nicolas; Leong, Kam W

    2016-04-01

    Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYH11, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction. PMID:26874281

  12. Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis

    PubMed Central

    Pitsouli, Chrysoula; Perrimon, Norbert

    2010-01-01

    Adult structures in holometabolous insects such as Drosophila are generated by groups of imaginal cells dedicated to the formation of different organs. Imaginal cells are specified in the embryo and remain quiescent until the larval stages, when they proliferate and differentiate to form organs. The Drosophila tracheal system is extensively remodeled during metamorphosis by a small number of airway progenitors. Among these, the spiracular branch tracheoblasts are responsible for the generation of the pupal and adult abdominal airways. To understand the coordination of proliferation and differentiation during organogenesis of tubular organs, we analyzed the remodeling of Drosophila airways during metamorphosis. We show that the embryonic spiracular branch tracheoblasts are multipotent cells that express the homeobox transcription factor Cut, which is necessary for their survival and normal development. They give rise to three distinct cell populations at the end of larval development, which generate the adult tracheal tubes, the spiracle and the epidermis surrounding the spiracle. Our study establishes the series of events that lead to the formation of an adult tubular structure in Drosophila. PMID:20940225

  13. The binary progenitor of Tycho Brahe's 1572 supernova.

    PubMed

    Ruiz-Lapuente, Pilar; Comeron, Fernando; Méndez, Javier; Canal, Ramon; Smartt, Stephen J; Filippenko, Alexei V; Kurucz, Robert L; Chornock, Ryan; Foley, Ryan J; Stanishev, Vallery; Ibata, Rodrigo

    2004-10-28

    The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova is one of only two type Ia supernovae observed in our Galaxy, and so provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova. PMID:15510140

  14. Therapeutic Roles of Tendon Stem/Progenitor Cells in Tendinopathy

    PubMed Central

    Zhang, Xin; Lin, Yu-cheng; Rui, Yun-feng; Xu, Hong-liang; Chen, Hui; Wang, Chen; Teng, Gao-jun

    2016-01-01

    Tendinopathy is a tendon disorder characterized by activity-related pain, local edema, focal tenderness to palpation, and decreased strength in the affected area. Tendinopathy is prevalent in both athletes and the general population, highlighting the need to elucidate the pathogenesis of this disorder. Current treatments of tendinopathy are both conservative and symptomatic. The discovery of tendon stem/progenitor cells (TSPCs) and erroneous differentiation of TSPCs have provided new insights into the pathogenesis of tendinopathy. In this review, we firstly present the histopathological characteristics of tendinopathy and explore the cellular and molecular cues in the pathogenesis of tendinopathy. Current evidence of the depletion of the stem cell pool and altered TSPCs fate in the pathogenesis of tendinopathy has been presented. The potential regulatory factors for either tenogenic or nontenogenic differentiation of TSPCs are also summarized. The regulation of endogenous TSPCs or supplementation with exogenous TSPCs as therapeutic targets for the treatment of tendinopathy is proposed. Therefore, inhibiting the erroneous differentiation of TSPCs and regulating the differentiation of TSPCs into tendon cells might be important areas of future research and could provide new clinical treatments for tendinopathy. The current evidence suggests that TSPCs are promising therapeutic targets for the management of tendinopathy. PMID:27195010

  15. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors

    PubMed Central

    Gautier, Hélène O. B.; Evans, Kimberley A.; Volbracht, Katrin; James, Rachel; Sitnikov, Sergey; Lundgaard, Iben; James, Fiona; Lao-Peregrin, Cristina; Reynolds, Richard; Franklin, Robin J. M.; Káradóttir, Ragnhildur T

    2015-01-01

    Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ∼6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination. PMID:26439639

  16. A Simple Approach to the Supernova Progenitor-Explosion Connection

    NASA Astrophysics Data System (ADS)

    Müller, Bernhard; Heger, Alexander; Liptai, David; Cameron, Joshua B.

    2016-05-01

    We present a new approach to understand the landscape of supernova explosion energies, ejected nickel masses, and neutron star birth masses. In contrast to other recent parametric approaches, our model predicts the properties of neutrino-driven explosions based on the pre-collapse stellar structure without the need for hydrodynamic simulations. The model is based on physically motivated scaling laws and simple differential equations describing the shock propagation, the contraction of the neutron star, the neutrino emission, the heating conditions, and the explosion energetics. Using model parameters compatible with multi-D simulations and a fine grid of thousands of supernova progenitors, we obtain a variegated landscape of neutron star and black hole formation similar to other parameterised approaches and find good agreement with semi-empirical measures for the "explodability" of massive stars. Our predicted explosion properties largely conform to observed correlations between the nickel mass and explosion energy. Accounting for the coexistence of outflows and downflows during the explosion phase, we naturally obtain a positive correlation between explosion energy and ejecta mass. These correlations are relatively robust against parameter variations, but our results suggest that there is considerable leeway in parametric models to widen or narrow the mass ranges for black hole and neutron star formation and to scale explosion energies up or down. Our model is currently limited to an all-or-nothing treatment of fallback and there remain some minor discrepancies between model predictions and observational constraints.

  17. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells.

    PubMed

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; MacLellan, W Robb; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  18. Is Ursa Major II the Progenitor of the Orphan Stream?

    SciTech Connect

    Fellhauer, M.; Evans, N.W.; Belokurov, V.; Zucker, D.B.; Yanny, B.; Wilkinson, M.I.; Gilmore, G.; Irwin, M.J.; Bramich, D.M.; Vidrih, S.; Hewett, Paul C.; /Cambridge U., Inst. of Astron. /Michigan State U.

    2006-11-01

    Prominent in the ''Field of Streams''--the Sloan Digital Sky Survey map of substructure in the Galactic halo--is an ''Orphan Stream'' without obvious progenitor. In this numerical study, we show a possible connection between the newly found dwarf satellite Ursa Major II (UMa II) and the Orphan Stream. We provide numerical simulations of the disruption of UMa II that match the observational data on the position, distance and morphology of the Orphan Stream. We predict the radial velocity of UMa II as -100kms{sup -1}, as well as the existence of strong velocity gradients along the Orphan Stream. The velocity dispersion of UMa II is expected to be high, though this can be caused both by a high dark matter content or by the presence of unbound stars in a disrupted remnant. However, the existence of a gradient in the mean radial velocity across UMa II provides a clear-cut distinction between these possibilities. The simulations support the idea that some of the anomalous, young halo globular clusters like Palomar 1 or Arp 2 or Ruprecht 106 may be physically associated with the Orphan Stream.

  19. Tamoxifen promotes differentiation of oligodendrocyte progenitors in vitro.

    PubMed

    Barratt, H E; Budnick, H C; Parra, R; Lolley, R J; Perry, C N; Nesic, O

    2016-04-01

    The most promising therapeutic approach to finding the cure for devastating demyelinating conditions is the identification of clinically safe pharmacological agents that can promote differentiation of endogenous oligodendrocyte precursor cells (OPCs). Here we show that the breast cancer medication tamoxifen (TMX), with well-documented clinical safety and confirmed beneficial effects in various models of demyelinating conditions, stimulates differentiation of rat glial progenitors to mature oligodendrocytes in vitro. Clinically applicable doses of TMX significantly increased both the number of CNPase-positive oligodendrocytes and protein levels of myelin basic protein, measured with Western blots. Furthermore, we also found that OPC differentiation was stimulated, not only by the pro-drug TMX-citrate (TMXC), but also by two main TMX metabolites, 4-hydroxy-TMX and endoxifen. Differentiating effects of TMXC and its metabolites were completely abolished in the presence of estrogen receptor (ER) antagonist, ICI182780. In contrast to TMXC and 4-hydroxy-TMX, endoxifen also induced astrogliogenesis, but independent of the ER activation. In sum, we showed that the TMX prodrug and its two main metabolites (4-hydroxy-TMX and endoxifen) promote ER-dependent oligodendrogenesis in vitro, not reported before. Given that differentiating effects of TMX were achieved with clinically safe doses, TMX is likely one of the most promising FDA-approved drugs for the possible treatment of demyelinating diseases. PMID:26820594

  20. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

    PubMed Central

    Yu, Cai-Guo; Zhang, Ning; Yuan, Sha-Sha; Ma, Yan; Yang, Long-Yan; Feng, Ying-Mei; Zhao, Dong

    2016-01-01

    Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics. PMID:27313624

  1. Eicosanoid Regulation of Hematopoiesis and Hematopoietic Stem and Progenitor Trafficking

    PubMed Central

    Hoggatt, Jonathan; Pelus, Louis M.

    2011-01-01

    Hematopoietic stem cell (HSC) transplantation is a potentially curative treatment for numerous hematologic malignancies. The transplant procedure as performed today takes advantage of HSC trafficking; either egress of HSC from the bone marrow to the peripheral blood, i.e. mobilization, for acquisition of the hematopoietic graft, and/or trafficking of HSC from the peripheral blood to bone marrow niches in the recipient patient, i.e. HSC homing. Numerous studies, many of which are reviewed herein, have defined hematopoietic regulatory mechanisms mediated by the 20-carbon lipid family of eicosanoids, and recent evidence strongly supports a role for eicosanoids in regulation of hematopoietic trafficking, adding a new role whereby eicosanoids regulate hematopoiesis. Short-term exposure of HSC to the eicosanoid prostaglandin E2 (PGE2) increases CXCR4 receptor expression, migration and in vivo homing of HSC. In contrast, cannabinoids reduce hematopoietic progenitor cell (HPC) CXCR4 expression and induce HPC mobilization when administered in vivo. Leukotrienes have been shown to alter CD34+ cell adhesion, migration, and regulate HSC proliferation, suggesting that eicosanoids have both opposing and complimentary roles in the regulation of hematopoiesis. Since numerous FDA approved compounds regulate eicosanoid signaling or biosynthesis, the utility of eicosanoid based therapeutic strategies to improve hematopoietic transplantation can be rapidly evaluated. PMID:20882043

  2. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

    PubMed

    Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

    2015-03-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI. PMID:25750747

  3. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development☆

    PubMed Central

    Abd El Aziz, M.T.; Abd El Nabi, E.A.; Abd El Hamid, M.; Sabry, D.; Atta, H.M.; Rahed, L.A.; Shamaa, A.; Mahfouz, S.; Taha, F.M.; Elrefaay, S.; Gharib, D.M.; Elsetohy, Khaled A.

    2013-01-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI. PMID:25750747

  4. Microenvironment influences vascular differentiation of murine cardiovascular progenitor cells.

    PubMed

    Gluck, Jessica M; Delman, Connor; Chyu, Jennifer; MacLellan, W Robb; Shemin, Richard J; Heydarkhan-Hagvall, Sepideh

    2014-11-01

    We examined the effects of the microenvironment on vascular differentiation of murine cardiovascular progenitor cells (CPCs). We isolated CPCs and seeded them in culture exposed to the various extracellular matrix (ECM) proteins in both two-dimensional (2D) and 3D culture systems. To better understand the contribution of the microenvironment to vascular differentiation, we analyzed endothelial and smooth muscle cell differentiation at both day 7 and day 14. We found that laminin and vitronectin enhanced vascular endothelial cell differentiation while fibronectin enhanced vascular smooth muscle cell differentiation. We also observed that the effects of the 3D electrospun scaffolds were delayed and not noticeable until the later time point (day 14), which may be due to the amount of time necessary for the cells to migrate to the interior of the scaffold. The study characterized the contributions of both ECM proteins and the addition of a 3D culture system to continued vascular differentiation. Additionally, we demonstrated the capability bioengineer a CPC-derived vascular graft. PMID:24687591

  5. SNLS: Constraints on SN Ia progenitors from host galaxies

    NASA Astrophysics Data System (ADS)

    Howell, D. A.; Sullivan, M.; Le Borgne, D.; Hodsman, A.; Astier, P.; Aubourg, E.; Balam, D.; Basa, S.; Carlberg, R. G.; Conley, A.; Fabbro, S.; Fouchez, D.; Guy, J.; Hook, I. M.; Lafoux, H.; Neill, J. D.; Pain, R.; Palanque-Delabrouille, N.; Perrett, K.; Pritchet, C. J.; Regnault, N.; Rich, J.; Taillet, R.; Baumont, S.; Bronder, T. J.; Filliol, M.; Perlmutter, S.; Tao, C.; SNLS Collaboration

    2005-12-01

    We investigate the single degenerate and double degenerate progenitor scenarios for SNe Ia using Pegase galaxy population synthesis models fit to the SN Ia host galaxy ugriz data from the SNLS. For the single degenerate scenario, we present the results of a Monte Carlo sumulation combining limits on the star formation history of the model hosts and analytic contraints on the allowable primary and secondary mass distributions. Under the assuption that all SNe are from the single degenerate channel, we find that SNe in star forming galaxies have a wide range of secondary masses, with a median of about 5 solar masses. Supernovae from the older galaxy population must come from a narrower distribution of secondary masses, with a median less than two solar masses. When combined with the differing stretch distributions for the two populations, this argues that there is a light curve shape-secondary mass correlation if the single degenerate model is the only route to an SN Ia. However, the single degenerate scenario has difficulty producing the observed SN Ia rate in old populations so the double degenerate scenario may be preferred.

  6. l-Arginine is a Radioprotector for Hematopoietic Progenitor Cells

    PubMed Central

    Pearce, Linda L.; Zheng, Xichen; Martinez-Bosch, Sandra; Kerr, Patrick P.; Khlangwiset, Pornsri; Epperly, Michael W.; Fink, Mitchell P.; Greenberger, Joel S.; Peterson, Jim

    2012-01-01

    l-Arginine is shown to protect hematopoietic progenitor (32D cl 3) cells from death due to exposure to γ radiation (137Cs). Some of the other intermediates in the urea cycle, namely ornithine and citrulline, plus urea itself, were not found to have any significant impact on cell survival after irradiation. Intriguingly, supplementation of irradiated cells with l-arginine results in decreased production of peroxynitrite, suggesting that suppression of superoxide generation by nitric oxide synthase in one or more microenvironments is an important factor in the observed radioprotection. The absence of any radioprotective effect of l-arginine in cells at 3% oxygen also confirms the involvement of one or more oxygen-derived species. Knockdown experiments with nitric oxide synthase (NOS) siRNAs in cells and NOS knockout animals confirm that the observed radioprotection is associated with nNOS (NOS-1). l-Arginine also ameliorates the transient inhibition of the electron-transport chain complex I that occurs within 30 min of completing the dose (10 Gy) and that appears to be a functional marker for postirradiation mitochondrial oxidant production. PMID:22175298

  7. Phagocytic activity of neuronal progenitors regulates adult neurogenesis.

    PubMed

    Lu, Zhenjie; Elliott, Michael R; Chen, Yubo; Walsh, James T; Klibanov, Alexander L; Ravichandran, Kodi S; Kipnis, Jonathan

    2011-09-01

    Whereas thousands of new neurons are generated daily during adult life, only a fraction of them survive and become part of neural circuits; the rest die, and their corpses are presumably cleared by resident phagocytes. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. Here, we identify an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo and ex vivo studies demonstrate that DCX(+) cells comprise a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX(+) cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild-type mice) led to reduced uptake by DCX(+) cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. Collectively, these findings indicate a paradigm wherein DCX(+) neuronal precursors also serve as phagocytes, and that their phagocytic activity critically contributes to neurogenesis in the adult brain. PMID:21804544

  8. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

    PubMed Central

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  9. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors.

    PubMed

    Gautier, Hélène O B; Evans, Kimberley A; Volbracht, Katrin; James, Rachel; Sitnikov, Sergey; Lundgaard, Iben; James, Fiona; Lao-Peregrin, Cristina; Reynolds, Richard; Franklin, Robin J M; Káradóttir, Ragnhildur T

    2015-01-01

    Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ∼6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination. PMID:26439639

  10. Myocardial infarction activates CCR2+ hematopoietic stem and progenitor cells

    PubMed Central

    Dutta, Partha; Sager, Hendrik B.; Stengel, Kristy R.; Naxerova, Kamila; Courties, Gabriel; Saez, Borja; Silberstein, Lev; Heidt, Timo; Sebas, Matthew; Sun, Yuan; Wojtkiewicz, Gregory; Feruglio, Paolo Fumene; King, Kevin; Baker, Joshua N.; van der Laan, Anja M.; Borodovsky, Anna; Fitzgerald, Kevin; Hulsmans, Maarten; Hoyer, Friedrich; Iwamoto, Yoshiko; Vinegoni, Claudio; Brown, Dennis; Di Carli, Marcelo; Libby, Peter; Hiebert, Scott; Scadden, David; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

    2015-01-01

    SUMMARY Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlate closely with mortality. The origin of these myeloid cells, and the response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is unclear. Here, we identify a CCR2+CD150+CD48− LSK hematopoietic subset as the most upstream contributor to emergency myelopoiesis after ischemic organ injury. CCR2+ HSPC have fourfold higher proliferation rates than CCR2−CD150+CD48− LSK cells, display a myeloid differentiation bias, and dominate the migratory HSPC population. We further demonstrate the myeloid translocation gene 16 (Mtg16) regulates CCR2+ HSPC emergence. Mtg16−/− mice have decreased levels of systemic monocytes and infarct-associated macrophages and display compromised tissue healing and post-MI heart failure. Together, these data provide insights into regulation of emergency hematopoiesis after ischemic injury, and identify potential therapeutic targets to modulate leukocyte output after MI. PMID:25957903

  11. Circulating Progenitor and Mature Endothelial Cells in Deep Vein Thrombosis

    PubMed Central

    Alessio, Aline M; Beltrame, Miriam P; Nascimento, Mariane C Flores; Vicente, Cristina P; de Godoy, Juliana AP; Silva, Junia CR Santos; Bittar, Luis Fernando; Lorand-Metze, Irene; de Paula, Erich V; Annichino-Bizzacchi, Joyce M

    2013-01-01

    Introduction: Mature circulating endothelial cells (CEC) and circulating endothelial progenitor cells (EPC) have been described in several conditions associated with endothelial injury. Their role in deep vein thrombosis (DVT) has not been previously evaluated. Patients and Methods: In this pilot study we evaluated the time course of CEC and EPC release after vena cava experimental DVT in mice, using the FeCl3 model. We also evaluated their presence in patients with DVT at different phases of the disease (acute and chronic phase). CEC and EPC were evaluated by Flow Cytometry. Results: In mice, both CEC and EPC were increased 24 hours after DVT induction, peaking 48 hours thereafter. After 72 hours, CEC counts decreased sharply, whereas EPC counts decreased less substantially. In DVT patients we observed a significant increase in CEC counts immediately after DVT compared to healthy individuals. Patients with chronic disease also presented a significant elevation of these cell count. In a subgroup of patients for whom serial samples were available, CEC counts decreased significantly after 9-15 months of the acute event. Conclusions: Our results suggest the participation of these cells in the reparative processes that follows DVT, both at immediate and late time-points. The different kinetics of CEC and EPC release in experimental DVT suggests a heterogeneous role for these cells in the reparative events after DVT. PMID:24155660

  12. Structure of merger remnants. II - Progenitors with rotating bulges

    NASA Technical Reports Server (NTRS)

    Hernquist, Lars

    1993-01-01

    Mergers of identical galaxies consisting of self-gravitating disks, bulges, and halos are examined in the context of the suggestion that such events may form elliptical galaxies. Unlike earlier studies, the simulations reported here include effects arising from intrinsic spin of bulges. It is found that the disks and bulges are able to redistribute their angular momentum so that the luminous remnants rotate slowly near their centers. In addition, if the bulges are sufficiently concentrated, the core radii of the remnants are significantly reduced relative to those of end-states formed in mergers between pure stellar disks to the extent that the remnants share structural properties with observed elliptical galaxies. Nevertheless, it does appear that stellar-dynamical mergers between spiral progenitors will represent a viable mechanism for the production of massive elliptical galaxies only if sufficient mass resides already in dense, spheroidal components. These results suggest that any ellipticals formed in this manner having featureless light profiles were victims of a 'disk-bulge conspiracy' analogous to the disk-halo conspiracy thought to give rise to smooth rotation curves in spiral galaxies. Possible observational signatures of mergers are discussed, along with implications of the findings for our understanding of galaxy formation and evolution.

  13. Neural stem/progenitor cells in Alzheimer’s disease

    PubMed Central

    Tincer, Gizem; Mashkaryan, Violeta; Bhattarai, Prabesh; Kizil, Caghan

    2016-01-01

    Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and a worldwide health challenge. Different therapeutic approaches are being developed to reverse or slow the loss of affected neurons. Another plausible therapeutic way that may complement the studies is to increase the survival of existing neurons by mobilizing the existing neural stem/progenitor cells (NSPCs) — i.e. “induce their plasticity” — to regenerate lost neurons despite the existing pathology and unfavorable environment. However, there is controversy about how NSPCs are affected by the unfavorable toxic environment during AD. In this review, we will discuss the use of stem cells in neurodegenerative diseases and in particular how NSPCs affect the AD pathology and how neurodegeneration affects NSPCs. In the end of this review, we will discuss how zebrafish as a useful model organism with extensive regenerative ability in the brain might help to address the molecular programs needed for NSPCs to respond to neurodegeneration by enhanced neurogenesis. PMID:27505014

  14. Requirement for Foxd3 in Maintenance of Neural Crest Progenitors

    PubMed Central

    Teng, Lu; Mundell, Nathan A.; Frist, Audrey Y.; Wang, Qiaohong; Labosky, Patricia A.

    2008-01-01

    Summary Understanding the molecular mechanisms of stem cell maintenance is critical for the ultimate goal of manipulating stem cells for treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3−/− embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue specific deletion of Foxd3 in the neural crest, we show that Foxd3flox/−; Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo. PMID:18367558

  15. Role of liver progenitors in acute liver injury

    PubMed Central

    Best, Jan; Dollé, Laurent; Manka, Paul; Coombes, Jason; van Grunsven, Leo A.; Syn, Wing-Kin

    2013-01-01

    Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte function and frequently exhibits a fulminant course, characterized by high mortality in the absence of immediate state-of-the-art intensive care and/or emergency liver transplantation (ELT). The role of hepatocyte-mediated liver regeneration during acute and chronic liver injury has been extensively investigated, and recent studies suggest that hepatocytes are not exclusively responsible for the regeneration of the injured liver during fulminant liver injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. This review aims to provide an overview of the role of the LPC population during ALF, and the role of putative cytokines, growth factors, mitogens, and hormones in the LPC response. We will highlight the potential interaction among cellular compartments during ALF, and discuss the possible prognostic value of the LPC response on ALF outcomes. PMID:24133449

  16. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

    PubMed

    Yu, Cai-Guo; Zhang, Ning; Yuan, Sha-Sha; Ma, Yan; Yang, Long-Yan; Feng, Ying-Mei; Zhao, Dong

    2016-01-01

    Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on "VEGF uncoupling with nitric oxide" and "competitive angiopoietin 1/angiopoietin 2" mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics. PMID:27313624

  17. A simple approach to the supernova progenitor-explosion connection

    NASA Astrophysics Data System (ADS)

    Müller, Bernhard; Heger, Alexander; Liptai, David; Cameron, Joshua B.

    2016-07-01

    We present a new approach to understand the landscape of supernova explosion energies, ejected nickel masses, and neutron star birth masses. In contrast to other recent parametric approaches, our model predicts the properties of neutrino-driven explosions based on the pre-collapse stellar structure without the need for hydrodynamic simulations. The model is based on physically motivated scaling laws and simple differential equations describing the shock propagation, the contraction of the neutron star, the neutrino emission, the heating conditions, and the explosion energetics. Using model parameters compatible with multi-D simulations and a fine grid of thousands of supernova progenitors, we obtain a variegated landscape of neutron star and black hole formation similar to other parametrized approaches and find good agreement with semi-empirical measures for the `explodability' of massive stars. Our predicted explosion properties largely conform to observed correlations between the nickel mass and explosion energy. Accounting for the coexistence of outflows and downflows during the explosion phase, we naturally obtain a positive correlation between explosion energy and ejecta mass. These correlations are relatively robust against parameter variations, but our results suggest that there is considerable leeway in parametric models to widen or narrow the mass ranges for black hole and neutron star formation and to scale explosion energies up or down. Our model is currently limited to an all-or-nothing treatment of fallback and there remain some minor discrepancies between model predictions and observational constraints.

  18. Hyperoxia, Endothelial Progenitor Cell Mobilization, and Diabetic Wound Healing

    PubMed Central

    Liu, Zhao-Jun

    2008-01-01

    Abstract Diabetic foot disease is a major health problem, which affects 15% of the 200 million patients with diabetes worldwide. Diminished peripheral blood flow and decreased local neovascularization are critical factors that contribute to the delayed or nonhealing wounds in these patients. The correction of impaired local angiogenesis may be a key component in developing therapeutic protocols for treating chronic wounds of the lower extremity and diabetic foot ulcers. Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal neovascularization and play a central role in wound healing, but their circulating and wound-level numbers are decreased in diabetes, implicating an abnormality in EPC mobilization and homing mechanisms. The deficiency in EPC mobilization is presumably due to impairment of eNOS-NO cascade in bone marrow (BM). Hyperoxia, induced by a clinically relevant hyperbaric oxygen therapy (HBO) protocol, can significantly enhance the mobilization of EPCs from the BM into peripheral blood. However, increased circulating EPCs failed to reach to wound tissues. This is partly a result of downregulated production of SDF-1α in local wound lesions with diabetes. Administration of exogenous SDF-1α into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, neovascularization, and wound healing. Antioxid. Redox Signal. 10, 1869–1882. PMID:18627349

  19. Perivascular support of human hematopoietic stem/progenitor cells

    PubMed Central

    Corselli, Mirko; Chin, Chee Jia; Parekh, Chintan; Sahaghian, Arineh; Wang, Wenyuan; Ge, Shundi; Evseenko, Denis; Wang, Xiaoyan; Montelatici, Elisa; Lazzari, Lorenza; Crooks, Gay M.

    2013-01-01

    Hematopoietic stem and progenitor cells (HSPCs) emerge and develop adjacent to blood vessel walls in the yolk sac, aorta-gonad-mesonephros region, embryonic liver, and fetal bone marrow. In adult mouse bone marrow, perivascular cells shape a “niche” for HSPCs. Mesenchymal stem/stromal cells (MSCs), which support hematopoiesis in culture, are themselves derived in part from perivascular cells. In order to define their direct role in hematopoiesis, we tested the ability of purified human CD146+ perivascular cells, as compared with unfractionated MSCs and CD146− cells, to sustain human HSPCs in coculture. CD146+ perivascular cells support the long-term persistence, through cell-to-cell contact and at least partly via Notch activation, of human myelolymphoid HSPCs able to engraft primary and secondary immunodeficient mice. Conversely, unfractionated MSCs and CD146− cells induce differentiation and compromise ex vivo maintenance of HSPCs. Moreover, CD146+ perivascular cells express, natively and in culture, molecular markers of the vascular hematopoietic niche. Unexpectedly, this dramatic, previously undocumented ability to support hematopoietic stem cells is present in CD146+ perivascular cells extracted from the nonhematopoietic adipose tissue. PMID:23412095

  20. Pericytes are progenitors for coronary artery smooth muscle.

    PubMed

    Volz, Katharina S; Jacobs, Andrew H; Chen, Heidi I; Poduri, Aruna; McKay, Andrew S; Riordan, Daniel P; Kofler, Natalie; Kitajewski, Jan; Weissman, Irving; Red-Horse, Kristy

    2015-01-01

    Epicardial cells on the heart's surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing to show that caSMCs derive from pericytes, mural cells associated with microvessels, and that these cells are present in adults. During development following the onset of blood flow, pericytes at arterial remodeling sites upregulate Notch3 while endothelial cells express Jagged-1. Deletion of Notch3 disrupts caSMC differentiation. Our data support a model wherein epicardial-derived pericytes populate the entire coronary microvasculature, but differentiate into caSMCs at arterial remodeling zones in response to Notch signaling. Our data are the first demonstration that pericytes are progenitors for smooth muscle, and their presence in adult hearts reveals a new potential cell type for targeting during cardiovascular disease. PMID:26479710

  1. Rotating Type Ia SN progenitors: explosion and light curves

    SciTech Connect

    Dominguez, I.; Piersanti, L.; Gagliardi, S.; Straniero, O.; Tornambe, A.; Bravo, E.

    2005-10-21

    High redshift SNe Ia have been recently used to calibrate the cosmological distance scale and to infer the existence of the dark energy. The reliability of such a method depends on the effective knowledge of the absolute brightness of this class of supernovae. This would require a complete understanding of the physics of SNeIa.Starting from an accreting rotating white dwarf, the only progenitor that we found to be able to grow till the Chandrasekhar mass and undergo a thermonuclear explosion, we simulate the explosion, deriving the nucleosynthesis and the light curve. We explore the final outcome in the framework of a 1D delayed detonation model, where the characteristic density for which the transition from deflagration to detonation takes place is a free parameter.Although preliminary, our results imply that rotating white dwarfs produce a range of explosive conditions, characterized by different ignition densities and total masses. Maximum luminosities of successfully explosive models differ up to 0.11 mag. In a few cases, the formation of a small highly neutronised remnant is found.

  2. The binary progenitor of Tycho Brahe's 1572 supernova

    NASA Astrophysics Data System (ADS)

    Ruiz-Lapuente, Pilar; Comeron, Fernando; Méndez, Javier; Canal, Ramon; Smartt, Stephen J.; Filippenko, Alexei V.; Kurucz, Robert L.; Chornock, Ryan; Foley, Ryan J.; Stanishev, Vallery; Ibata, Rodrigo

    2004-10-01

    The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova is one of only two type Ia supernovae observed in our Galaxy, and so provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.

  3. Tbx16 regulates hox gene activation in mesodermal progenitor cells.

    PubMed

    Payumo, Alexander Y; McQuade, Lindsey E; Walker, Whitney J; Yamazoe, Sayumi; Chen, James K

    2016-09-01

    The transcription factor T-box 16 (Tbx16, or Spadetail) is an essential regulator of paraxial mesoderm development in zebrafish (Danio rerio). Mesodermal progenitor cells (MPCs) fail to differentiate into trunk somites in tbx16 mutants and instead accumulate within the tailbud in an immature state. However, the mechanisms by which Tbx16 controls mesoderm patterning have remained enigmatic. We describe here the use of photoactivatable morpholino oligonucleotides to determine the Tbx16 transcriptome in MPCs. We identified 124 Tbx16-regulated genes that were expressed in zebrafish gastrulae, including several developmental signaling proteins and regulators of gastrulation, myogenesis and somitogenesis. Unexpectedly, we observed that a loss of Tbx16 function precociously activated posterior hox genes in MPCs, and overexpression of a single posterior hox gene was sufficient to disrupt MPC migration. Our studies support a model in which Tbx16 regulates the timing of collinear hox gene activation to coordinate the anterior-posterior fates and positions of paraxial MPCs. PMID:27376691

  4. Endothelial progenitor cell recruitment in a microfluidic vascular model.

    PubMed

    Lewis, Daniel M; Abaci, Hasan E; Xu, Yu; Gerecht, Sharon

    2015-12-01

    During vessel injury, endothelial progenitors cells (EPCs) are recruited from bone marrow and directed to the hypoxic injury site. The hypoxic conditions in the damaged blood vessel promote TNF-α, which upregulates intercellular adhesion molecule-1 (ICAM-1). EPCs attach to endothelial cell lining using ICAM-1. Here we aimed to examine EPC attachment to ECs in an injured-blood vessel conditions. We first determined ICAM-1 expression in stimulated HUVECs. We stimulated HUVECs with 21% oxygen (atmospheric), atmospheric with TNF-α-supplemented media, 1% oxygen (hypoxia), and hypoxia with TNF-α-supplemented media and found the highest ECFC attachment on HUVECs stimulated with TNF-α and hypoxia, correlating with the highest ICAM-1 expression. We next designed, fabricated and tested a three-dimensional microbioreactor (3D MBR) system with precise control and monitoring of dissolve oxygen and media flow rate in the cellular environment. We utilized a step-wise seeding approach, producing monolayer of HUVECs on all four walls. When stimulated with both TNF-α and hypoxia, ECFC retention on HUVECs was significantly increased under low shear stress compared to static controls. Overall, the 3D MBR system mimics the pathological oxygen tension and shear stress in the damaged vasculature, providing a platform to model vascular-related disorders. PMID:26693599

  5. Type 2 Diabetes Dysregulates Glucose Metabolism in Cardiac Progenitor Cells.

    PubMed

    Salabei, Joshua K; Lorkiewicz, Pawel K; Mehra, Parul; Gibb, Andrew A; Haberzettl, Petra; Hong, Kyung U; Wei, Xiaoli; Zhang, Xiang; Li, Qianhong; Wysoczynski, Marcin; Bolli, Roberto; Bhatnagar, Aruni; Hill, Bradford G

    2016-06-24

    Type 2 diabetes is associated with increased mortality and progression to heart failure. Recent studies suggest that diabetes also impairs reparative responses after cell therapy. In this study, we examined potential mechanisms by which diabetes affects cardiac progenitor cells (CPCs). CPCs isolated from the diabetic heart showed diminished proliferation, a propensity for cell death, and a pro-adipogenic phenotype. The diabetic CPCs were insulin-resistant, and they showed higher energetic reliance on glycolysis, which was associated with up-regulation of the pro-glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3). In WT CPCs, expression of a mutant form of PFKFB, which mimics PFKFB3 activity and increases glycolytic rate, was sufficient to phenocopy the mitochondrial and proliferative deficiencies found in diabetic cells. Consistent with activation of phosphofructokinase in diabetic cells, stable isotope carbon tracing in diabetic CPCs showed dysregulation of the pentose phosphate and glycero(phospho)lipid synthesis pathways. We describe diabetes-induced dysregulation of carbon partitioning using stable isotope metabolomics-based coupling quotients, which relate relative flux values between metabolic pathways. These findings suggest that diabetes causes an imbalance in glucose carbon allocation by uncoupling biosynthetic pathway activity, which could diminish the efficacy of CPCs for myocardial repair. PMID:27151219

  6. Role of osteoclasts in regulating hematopoietic stem and progenitor cells

    PubMed Central

    Miyamoto, Takeshi

    2013-01-01

    Bone marrow (BM) cavities are utilized for hematopoiesis and to maintain hematopoietic stem cells (HSCs). HSCs have the ability to self-renew as well as to differentiate into multiple different hematopoietic lineage cells. HSCs produce their daughter cells throughout the lifespan of individuals and thus, maintaining HSCs is crucial for individual life. BM cavities provide a specialized microenvironment termed “niche” to support HSCs. Niches are composed of various types of cells such as osteoblasts, endothelial cells and reticular cells. Osteoclasts are unique cells which resorb bones and are required for BM cavity formation. Loss of osteoclast function or differentiation results in inhibition of BM cavity formation, an osteopetrotic phenotype. Osteoclasts are also reportedly required for hematopoietic stem and progenitor cell (HSPC) mobilization to the periphery from BM cavities. Thus, lack of osteoclasts likely results in inhibition of HSC maintenance and HSPC mobilization. However, we found that osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization by using three independent osteoclast-less animal models. In this review, I will discuss the roles of osteoclasts in hematopoietic stem cell maintenance and mobilization. PMID:24147255

  7. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.

    PubMed

    Rudzitis-Auth, Jeannette; Nenicu, Anca; Nickels, Ruth M; Menger, Michael D; Laschke, Matthias W

    2016-08-01

    The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis. PMID:27315780

  8. Effects of shear stress on endothelial progenitor cells.

    PubMed

    Obi, Syotaro; Yamamoto, Kimiko; Ando, Joji

    2014-10-01

    Endothelial progenitor cells (EPCs) are adult stem cells that play a central role in neovascularization. EPCs are mobilized from bone marrow into peripheral blood, attach to existing endothelial cells, and then transmigrate across the endothelium into tissues, where they proliferate, differentiate, and form new blood vessels. In the process, EPCs are exposed to shear stress, a biomechanical force generated by flowing blood and tissue fluid flow. When cultured EPCs are exposed to controlled levels of shear stress in a flow-loading device, their bioactivities in terms of proliferation, anti-apoptosis, migration, production of bioactive substances, anti-thrombosis, and tube formation increase markedly. Expression of endothelial marker genes and proteins by EPCs also increases in response to shear stress, and they differentiate into mature endothelial cells. Great advances have been made in elucidating the mechanisms by which mature endothelial cells sense and respond to shear stress, but not in EPCs. Further study of EPC responses to shear stress will be necessary to better understand the physiological and pathophysiological roles of EPCs and to apply EPCs to new therapies in the field of regenerative medicine. PMID:25992410

  9. JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny

    PubMed Central

    2012-01-01

    Background It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB). Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression

  10. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Hedgehog-induced medulloblastoma

    PubMed Central

    Schüller, Ulrich; Heine, Vivi M.; Mao, Junhao; Kho, Alvin T.; Dillon, Allison K.; Han, Young-Goo; Huillard, Emmanuelle; Sun, Tao; Ligon, Azra H.; Qian, Ying; Ma, Qiufu; Alvarez-Buylla, Arturo; McMahon, Andrew P.; Rowitch, David H.; Ligon, Keith L.

    2008-01-01

    Origins of the brain tumor, medulloblastoma, from stem cells or restricted progenitor cells are unclear. To investigate this, we activated oncogenic Hedgehog (Hh) signaling in multipotent and lineage-restricted CNS progenitors. We observed that normal unipotent cerebellar granule neuron precursors (CGNP) derive from hGFAP+ and Olig2+ RL progenitors. Hh activation in a spectrum of early and late stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and that they retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hh signaling promotes medulloblastoma from lineage-restricted granule cell progenitors. PMID:18691547

  11. Use of long-term human marrow cultures to demonstrate progenitor cell precursors in marrow treated with 4-hydroperoxycyclophosphamide

    SciTech Connect

    Winton, E.F.; Colenda, K.W.

    1987-07-01

    The continued retrieval of progenitor cells (CFU-GEMM, BFU-E, CFU-E, CFU-GM) from human long-term marrow cultures (LTMC) is not uncommonly used as evidence that proliferation and differentiation are occurring in more primitive hematopoietic stem cells (HSC) in these cultures. Alternatively, the continued presence of progenitors in LTMC could be the result of survival and/or limited self-renewal of progenitor cells present when the culture was initiated, and such progenitors would have little relevance to the parent HSC. The following studies were designed to determine the relative contributions of precursors of progenitor cells to the total progenitor cells present in LTMC using a two-stage regeneration model. The adherent layer in LTMC was established over 3 weeks, irradiated (875 rad) to permanently eliminate resident hematopoietic cells, and recharged with autologous cryo-preserved marrow that was either treated or not treated (control) with 4-hydroperoxycyclophosphamide (4-HC, 100 micrograms/ml for 30 min). The 4-HC-treated marrow contained no progenitor cells, yet based on clinical autologous bone marrow transplant experience, has intact HSC. Within 1-3 weeks, progenitor cells reappeared in the irradiated LTMC recharged with 4-HC-treated marrow, and were preferentially located in the adherent layer. By 2-6 weeks, the number of progenitor cells in the adherent layer of LTMC recharged with 4-HC marrow was equivalent to control LTMC. The progenitors regenerating in the irradiated LTMC recharged with 4-HC-treated marrow appear to originate from precursors of progenitor cells, perhaps HSC. We propose this model may be useful in elucidating cellular and molecular correlates of progenitor cell regeneration from precursors.

  12. Transplanted human bone marrow progenitor subtypes stimulate endogenous islet regeneration and revascularization.

    PubMed

    Bell, Gillian I; Broughton, Heather C; Levac, Krysta D; Allan, David A; Xenocostas, Anargyros; Hess, David A

    2012-01-01

    Transplanted murine bone marrow (BM) progenitor cells recruit to the injured pancreas and induce endogenous beta cell proliferation to improve islet function. To enrich for analogous human progenitor cell types that stimulate islet regeneration, we purified human BM based on high-aldehyde dehydrogenase activity (ALDH(hi)), an enzymatic function conserved in hematopoietic, endothelial, and mesenchymal progenitor lineages. We investigated the contributions of ALDH(hi) mixed progenitor cells or culture-expanded, ALDH-purified multipotent stromal cell (MSC) subsets to activate endogenous programs for islet regeneration after transplantation into streptozotocin-treated NOD/SCID mice. Intravenous injection of uncultured BM ALDH(hi) cells improved systemic hyperglycemia and augmented insulin secretion by increasing islet size and vascularization, without increasing total islet number. Augmented proliferation within regenerated endogenous islets and associated vascular endothelium indicated the induction of islet-specific proliferative and pro-angiogenic programs. Although cultured MSC from independent human BM samples showed variable capacity to improve islet function, and prolonged expansion diminished hyperglycemic recovery, transplantation of ALDH-purified regenerative MSC reduced hyperglycemia and augmented total beta cell mass by stimulating the formation of small beta cell clusters associated with the ductal epithelium, without evidence of increased islet vascularization or Ngn3(+) endocrine precursor activation. Thus, endogenous islet recovery after progenitor cell transplantation can occur via distinct regenerative mechanisms modulated by subtypes of progenitor cells administered. Further, understanding of how these islet regenerative and pro-angiogenic programs are activated by specific progenitor subsets may provide new approaches for combination cellular therapies to combat diabetes. PMID:21417581

  13. Lineage Tracing of Resident Tendon Progenitor Cells during Growth and Natural Healing

    PubMed Central

    Dyment, Nathaniel A.; Hagiwara, Yusuke; Matthews, Brya G.; Li, Yingcui; Kalajzic, Ivo; Rowe, David W.

    2014-01-01

    Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1) an inducible Cre driven by alpha smooth muscle actin (SMACreERT2), that identifies mesenchymal progenitors, 2) a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre), a critical regulator of joint condensation, in combination with 3) an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+) cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies. PMID:24759953

  14. Stellar Forensics: A post-explosion view of the progenitors of core-collapse supernovae

    NASA Astrophysics Data System (ADS)

    Maund, Justyn

    2009-07-01

    Recent studies have used high spatial resolution HST observations of SN sites to identify the progenitors of core-collapse SNe on pre-explosion images. These studies have set constraints about the nature of massive stars and their evolution just prior to their explosion as SNe. Now, at late-times when the SNe have faded sufficiently, it is possible to return to the sites of these core-collapse SNe to search for clues about the nature of their progenitors.We request time to conduct deep, late-time, high-resolution imaging with ACS/HRC of the sites of six core-collapse SNe. In this program we aim to: 1} confirm our identifications, that were made with HST pre-explosion images, of the red supergiant progenitors of four Type IIP SNe {1999ev, 2003gd, 2004A and 2005cs}, by observing if the objects identified as the progenitors are now missing; 2} place precise constraints on the progenitor of the Type Ic SN 2007gr by studying its host cluster; and 3} confirm our identification of an LBV-like outburst of an unstable WR star as belonging to the progenitor of a Type Ib-n core-collapse SN {2006jc}, using broad and narrow-band imaging to search for emission line stars in its locality. The deep imaging will also allow to probe the stellar populations in the immediate vicinities of these SNe, that were previously obscured by the progenitors and the bright SNe. HST provides the unique combination of high-resolution optical imaging at very faint magnitudes that will facilitate this study.

  15. Stellar Forensics II: A post-explosion view of the progenitors of core-collapse supernovae

    NASA Astrophysics Data System (ADS)

    Maund, Justyn

    2010-09-01

    Recent studies have used high spatial resolution HST observations of supernova {SN} sites to directly identify the progenitors of core-collapse SNe on pre-explosion images. These studies have set constraints about the nature of massive stars and their evolution just prior to their explosion as SNe. Now, at late-times when the SNe have faded sufficiently, it is possible to return to the sites of these core-collapse SNe to search for clues about the nature of their progenitors.We request time to conduct deep, late-time, high-resolution imaging with WFC3/UVIS+IR and ACS/WFC of the sites of three core-collapse SNe 2008ax, 2008bk and 2008cn. We aim to: 1} Confirm our original identifications, made in pre-explosion images, by confirming that the progenitors are now missing; 2} Apply image subtraction techniques for this late-time imaging with our pre-explosion images to determine accurate photometry of the progenitors to constrain their temperatures and luminosities; and 3} study the stellar populations in the immediate vicinities of these SNe, previously obscured by the progenitor and the SN, to provide a measure of the progenitor's age, as well. For SN 2008ax we aim to determine the possible presence of a binary companion, as a persistent source at the SN location once the SN has faded and the progenitor has disappeared. HST provides the unique combination of high-resolution optical/IR imaging at very faint magnitudes that will facilitate this study.

  16. Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation

    PubMed Central

    Zhao, Chen; Guo, Hua; Li, Jingjing; Myint, Thomas; Pittman, William; Yang, Le; Zhong, Weimin; Schwartz, Robert J.; Schwarz, John J.; Singer, Harold A.; Tallquist, Michelle D.; Wu, Mingfu

    2014-01-01

    Numb family proteins (NFPs), including Numb and numb-like (Numbl), are cell fate determinants for multiple progenitor cell types. Their functions in cardiac progenitor differentiation and cardiac morphogenesis are unknown. To avoid early embryonic lethality and study NFP function in later cardiac development, Numb and Numbl were deleted specifically in heart to generate myocardial double-knockout (MDKO) mice. MDKOs were embryonic lethal and displayed a variety of defects in cardiac progenitor differentiation, cardiomyocyte proliferation, outflow tract (OFT) and atrioventricular septation, and OFT alignment. By ablating NFPs in different cardiac populations followed by lineage tracing, we determined that NFPs in the second heart field (SHF) are required for OFT and atrioventricular septation and OFT alignment. MDKOs displayed an SHF progenitor cell differentiation defect, as revealed by a variety of methods including mRNA deep sequencing. Numb regulated cardiac progenitor cell differentiation in an endocytosis-dependent manner. Studies including the use of a transgenic Notch reporter line showed that Notch signaling was upregulated in the MDKO. Suppression of Notch1 signaling in MDKOs rescued defects in p57 expression, proliferation and trabecular thickness. Further studies showed that Numb inhibits Notch1 signaling by promoting the degradation of the Notch1 intracellular domain in cardiomyocytes. This study reveals that NFPs regulate trabecular thickness by inhibiting Notch1 signaling, control cardiac morphogenesis in a Notch1-independent manner, and regulate cardiac progenitor cell differentiation in an endocytosis-dependent manner. The function of NFPs in cardiac progenitor differentiation and cardiac morphogenesis suggests that NFPs might be potential therapeutic candidates for cardiac regeneration and congenital heart diseases. PMID:24335256

  17. The Type IIb Supernova 2013df and its Cool Supergiant Progenitor

    NASA Technical Reports Server (NTRS)

    VanDyk, Schuyler D.; Zeng, Weikang; Fox, Ori D.; Cenko, S. Bradley; Clubb, Kelsey I.; Filippenko, Alexei; Foley, Ryan J.; Miller, Adam A.; Smith, Nathan; Kelly, Patrick L.; Lee, William H.; Ben-Ami, Sagi; Gal-Yam, Avishay

    2014-01-01

    We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type II b, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less Ni-56 (is approximately less than 0.06M) was synthesized in the SN 2013df explosion than was the case for the SNe II b 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013dfis estimated to be A(sub V) = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope(HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature T(sub eff) = 4250+/-100 K and a bolometric luminosity L(sub bol) =10(exp 4.94+/-0.06) Solar Luminosity. This leads to an effective radius Reff = 545+/-65 Solar Radius. The star likely had an initial mass in the range of 13-17Solar Mass; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J.

  18. Can pancreatic duct-derived progenitors be a source of islet regeneration?

    SciTech Connect

    Xia, Bing; Zhan, Xiao-Rong; Yi, Ran; Yang, Baofeng

    2009-06-12

    The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing {beta}-cells. The functional mass of {beta}-cells is decreased in type 1 diabetes, so replacing missing {beta}-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the {beta}-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding {beta}-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet {beta}-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as

  19. The type IIb supernova 2013df and its cool supergiant progenitor

    SciTech Connect

    Van Dyk, Schuyler D.; Cenko, S. Bradley; Foley, Ryan J.; Miller, Adam A.; Smith, Nathan; Lee, William H.; Ben-Ami, Sagi; Gal-Yam, Avishay

    2014-02-01

    We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type IIb, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less {sup 56}Ni (≲ 0.06 M {sub ☉}) was synthesized in the SN 2013df explosion than was the case for the SNe IIb 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013df is estimated to be A{sub V} = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope (HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature T {sub eff} = 4250 ± 100 K and a bolometric luminosity L {sub bol} = 10{sup 4.94±0.06} L {sub ☉}. This leads to an effective radius R {sub eff} = 545 ± 65 R {sub ☉}. The star likely had an initial mass in the range of 13-17 M {sub ☉}; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J.

  20. Induced Pluripotent Stem Cell-Derived Cardiac Progenitors Differentiate to Cardiomyocytes and Form Biosynthetic Tissues

    PubMed Central

    Chakraborty, Syandan; Chellapan, Malathi; Bursac, Nenad; Leong, Kam W.

    2013-01-01

    The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS) cells, which once differentiated allow for the enrichment of Nkx2-5(+) cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+) cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors’ ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological screening and

  1. Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats

    PubMed Central

    2013-01-01

    Background Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE). Methods SE was induced with pilocarpine in Sprague–Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining. Results After SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895. Conclusions An increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy. PMID:23339567

  2. Submillimeter galaxies as progenitors of compact quiescent galaxies

    SciTech Connect

    Toft, S.; Zirm, A.; Krogager, J.-K.; Man, A. W. S.; Smolčić, V.; Krpan, J.; Magnelli, B.; Karim, A.; Michalowski, M.; Capak, P.; Sheth, K.; Schawinski, K.; Wuyts, S.; Lutz, D.; Staguhn, J.; Berta, S.; Sanders, D.; Mccracken, H.; Riechers, D.

    2014-02-20

    Three billion years after the big bang (at redshift z = 2), half of the most massive galaxies were already old, quiescent systems with little to no residual star formation and extremely compact with stellar mass densities at least an order of magnitude larger than in low-redshift ellipticals, their descendants. Little is known about how they formed, but their evolved, dense stellar populations suggest formation within intense, compact starbursts 1-2 Gyr earlier (at 3 < z < 6). Simulations show that gas-rich major mergers can give rise to such starbursts, which produce dense remnants. Submillimeter-selected galaxies (SMGs) are prime examples of intense, gas-rich starbursts. With a new, representative spectroscopic sample of compact, quiescent galaxies at z = 2 and a statistically well-understood sample of SMGs, we show that z = 3-6 SMGs are consistent with being the progenitors of z = 2 quiescent galaxies, matching their formation redshifts and their distributions of sizes, stellar masses, and internal velocities. Assuming an evolutionary connection, their space densities also match if the mean duty cycle of SMG starbursts is 42{sub −29}{sup +40} Myr (consistent with independent estimates), which indicates that the bulk of stars in these massive galaxies were formed in a major, early surge of star formation. These results suggest a coherent picture of the formation history of the most massive galaxies in the universe, from their initial burst of violent star formation through their appearance as high stellar-density galaxy cores and to their ultimate fate as giant ellipticals.

  3. Submillimeter Galaxies as Progenitors of Compact Quiescent Galaxies

    NASA Technical Reports Server (NTRS)

    Toft, S.; Smolcic, V.; Magnelli, B.; Karim, A.; Zirm, A.; Michalowski, M.; Capak, P.; Sheth, K.; Schawinski, K.; Krogager, J.-K.; Wuyts, S.; Sanders, D.; Man, A. W. S.; Lutz, D.; Staguhn, J.; Berta, S.; McCracken, H.; Krpan, J.; Riechers, D.

    2014-01-01

    Three billion years after the big bang (at redshift z = 2), half of the most massive galaxies were already old, quiescent systems with little to no residual star formation and extremely compact with stellar mass densities at least an order of magnitude larger than in low-redshift ellipticals, their descendants. Little is known about how they formed, but their evolved, dense stellar populations suggest formation within intense, compact starbursts 1-2 Gyr earlier (at 3 < z < 6). Simulations show that gas-rich major mergers can give rise to such starbursts, which produce dense remnants. Submillimeter-selected galaxies (SMGs) are prime examples of intense, gas-rich starbursts.With a new, representative spectroscopic sample of compact, quiescent galaxies at z = 2 and a statistically well-understood sample of SMGs, we show that z = 3-6 SMGs are consistent with being the progenitors of z = 2 quiescent galaxies, matching their formation redshifts and their distributions of sizes, stellar masses, and internal velocities. Assuming an evolutionary connection, their space densities also match if the mean duty cycle of SMG starbursts is 42(sup+40) -29 Myr (consistent with independent estimates), which indicates that the bulk of stars in these massive galaxies were formed in a major, early surge of star formation. These results suggest a coherent picture of the formation history of the most massive galaxies in the universe, from their initial burst of violent star formation through their appearance as high stellar-density galaxy cores and to their ultimate fate as giant ellipticals.

  4. Ca(2+) Signalling in Endothelial Progenitor Cells: Friend or Foe?

    PubMed

    Moccia, Francesco; Guerra, Germano

    2016-02-01

    Endothelial progenitor cells (EPCs) are mobilized either from the bone marrow and/or the arterial to replace dysfunctional endothelial cells and rescue blood perfusion in ischemic tissues. In addition, they may contribute to the angiogenic switch, thereby sustaining tumour growth and metastatization. Understanding the molecular mechanisms utilized by vascular endothelial growth factor (VEGF) to stimulate EPCs might unveil novel targets to enhance their clinical outcome in regenerative medicine and to adverse tumour vascularisation. VEGF stimulates peripheral blood-derived EPCs to undergo repetitive Ca(2+) oscillations shaped by the interaction between inositol-1,4,5-trisphosphate (InsP3 )-dependent Ca(2+) release and store-operated Ca(2+) entry (SOCE). However, the Ca(2+) machinery underlying VEGF-induced Ca(2+) spikes changes in umbilical cord blood-derived EPCs, which require TRPC3-mediated Ca(2+) entry to trigger the interplay between InsP3 and SOCE. Surprisingly, VEGF fails to elicit pro-angiogenic Ca(2+) signals when EPCs derive from renal cellular carcinoma patients, thus questioning the suitability of VEGFR-2 as a target for anti-angiogenic treatments in these individuals. The lack of response to VEGF is likely due to the dramatic rearrangement of the Ca(2+) toolkit occurring in RCC-derived EPCs. Finally, primary myelofibrosis-derived EPCs display a further pattern of reorganization of the Ca(2+) machinery and proliferate independently of SOCE. Thus, the Ca(2+) machinery in human ECFCs is extremely plastic and may change depending on the physio-pathological background of the donor. As a consequence, the Ca(2+) toolkit could properly be used to enhance the regenerative outcome of cell-based therapy or adverse tumor vascularisation. PMID:26247172

  5. Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites.

    PubMed

    Hung, Huey-Shan; Yang, Yi-Chun; Lin, Yu-Chun; Lin, Shinn-Zong; Kao, Wei-Chien; Hsieh, Hsien-Hsu; Chu, Mei-Yun; Fu, Ru-Huei; Hsu, Shan-hui

    2014-08-01

    The mobilization and homing of endothelial progenitor cells (EPCs) are critical to the development of an antithrombotic cardiovascular prosthesis. Polyurethane (PU) with superior elasticity may provide a mechanical environment resembling that of the natural vascular tissues. The topographical cues of PU were maximized by making nanocomposites with a small amount of gold nanoparticles (AuNPs). The nanocomposites of PU-AuNPs ("PU-Au") with a favorable response of endothelial cells were previously established. In the current study, the effect of PU and PU-Au nanocomposites on the behavior of human peripheral blood EPCs was investigated in vitro and in vivo. It was found that PU-Au promoted EPCs to become differentiated endothelial cells in vitro, confirmed by the increased expressions of CD31 and VEGF-R2 surface markers. The increased maturation of EPCs was significantly more remarkable on PU-Au, probably through the stromal derived factor 1α (SDF-1α)/CXCR4 signaling pathway. In vivo experiments showed that EPCs seeded on PU-Au coated catheters effectively reduced thrombosis by differentiation into endothelial cells. Surface endothelialization with CD31 and CD34 expression as well as intimal formation with α-SMA expression was significantly accelerated in the group receiving EPC-seeded PU-Au catheters. Moreover, the analysis of collagen deposition revealed a reduction of fibrosis in the group receiving EPC-seeded PU-Au catheters as compared to the other groups. These results suggest that EPCs engineered with a proper elastic substrate may provide unique endothelialization and antithrombogenic properties that benefit vascular tissue regeneration. PMID:24836305

  6. Direct Confirmation of Intracluster Stars as SN Ia Progenitors

    NASA Astrophysics Data System (ADS)

    Zaritsky, Dennis

    2012-10-01

    To help resolve the progenitor problem for Type Ia supernovae {SNe Ia} and ensure their dependability as cosmological standard candles, we seek direct confirmation that SNe Ia explode in >2 Gyr old stellar populations. The Multi-Epoch Nearby Cluster Survey {MENeaCS} monitored 60 low redshift, rich galaxy clusters for two years, and spectroscopically confirmed four apparently hostless cluster SNe Ia. The intracluster medium hosts a purer population of old stars than elliptical galaxies, which have been shown to often harbor low levels of star formation. We propose to obtain deep HST images at the locations of these four SNe Ia {now faded}, to confirm that they are truly associated with the population of intracluster stars, and not hosted by a faint cluster galaxy or globular cluster. This proposal will also provide the necessary support for the use of IC SNe - as bright representatives of IC stars - in determining the fraction of IC stellar mass and light, which has low surface brightness and is difficult to measure directly. The required observations are only possible with HST, which has both the necessary resolution to limit contamination from background sources, and the sensitivity to detect or rule out the presence of a faint cluster galaxy or globular cluster at the SNe Ia locations. We have now been authorized to obtain parallel observations with WFC3. We use the same filters and the same exposure times as our ACS images. This data will provide additional cluster faint source number counts for our statistical analysis of any detection at our targeted coordinates, and contribute to our auxiliary science goals.

  7. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

    PubMed Central

    Colangelo, Donato; Gregoletto, Luca; Reano, Simone; Pietronave, Stefano; Merlin, Simone; Talmon, Maria; Novelli, Eugenio; Diena, Marco; Nicoletti, Carmine; Musarò, Antonio; Filigheddu, Nicoletta; Follenzi, Antonia; Prat, Maria

    2015-01-01

    A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol. PMID:26375957

  8. Cardiac Progenitor Cell Cycling Stimulated by Pim-1 Kinase

    PubMed Central

    Cottage, Christopher T.; Bailey, Brandi; Fischer, Kimberlee M.; Avitable, Daniele; Collins, Brett; Tuck, Savilla; Quijada, Pearl; Gude, Natalie; Alvarez, Roberto; Muraski, John; Sussman, Mark A.

    2011-01-01

    Rationale Cardioprotective effects of Pim-1 kinase have been previously reported but the underlying mechanistic basis may involve a combination of cellular and molecular mechanisms that remain unresolved. The elucidation of the mechanistic basis for Pim-1 mediated cardioprotection provides important insights for designing therapeutic interventional strategies to treat heart disease. Objective Effects of cardiac-specific Pim-1 kinase expression on the cardiac progenitor cell (CPC) population were examined to determine whether Pim-1 mediates beneficial effects through augmenting CPC activity. Methods and Results Transgenic mice created with cardiac-specific Pim-1 overexpression (Pim-wt) exhibit enhanced Pim-1 expression in both cardiomyocytes and CPCs, both of which show increased proliferative activity assessed using 5-bromodeoxyuridine (BrdU), Ki-67, and c-Myc relative to nontransgenic controls. However, the total number of CPCs was not increased in the Pim-wt hearts during normal postnatal growth or after infarction challenge. These results suggest that Pim-1 overexpression leads to asymmetric division resulting in maintenance of the CPC population. Localization and quantitation of cell fate determinants Numb and α-adaptin by confocal microscopy were used to assess frequency of asymmetric division in the CPC population. Polarization of Numb in mitotic phospho-histone positive cells demonstrates asymmetric division in 65% of the CPC population in hearts of Pim-wt mice versus 26% in nontransgenic hearts after infarction challenge. Similarly, Pim-wt hearts had fewer cells with uniform α-adaptin staining indicative of symmetrically dividing CPCs, with 36% of the CPCs versus 73% in nontransgenic sections. Conclusions These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase. PMID:20075333

  9. Nucleostemin Rejuvenates Cardiac Progenitor Cells and Antagonizes Myocardial Aging

    PubMed Central

    Hariharan, Nirmala; Quijada, Pearl; Mohsin, Sadia; Joyo, Anya; Samse, Kaitlen; Monsanto, Megan; De La Torre, Andrea; Avitabile, Daniele; Ormachea, Lucia; McGregor, Michael J.; Tsai, Emily J; Sussman, Mark A.

    2015-01-01

    BACKGROUND Functional decline in stem cell-mediated regeneration contributes to aging associated with cellular senescence in c-kit+ cardiac progenitor cells (CPCs). Clinical implementation of CPC-based therapy with elderly patients would benefit tremendously from understanding molecular characteristics of senescence to antagonize aging. Nucleostemin (NS) is a nucleolar protein regulating stem cell proliferation and pluripotency. OBJECTIVES The goal is to demonstrate that NS preserves characteristics associated with “stemness” in CPCs and antagonizes myocardial senescence and aging. METHODS CPCs isolated from human fetal (FhCPC) and adult failing (AhCPC) hearts, as well as young (YCPC) and old mice (OCPC), were studied for senescence characteristics and NS expression. Heterozygous knockout mice with one functional allele of NS (NS+/−) were used to demonstrate that NS preserves myocardial structure and function and slows characteristics of aging. RESULTS NS expression is decreased in AhCPCs relative to FhCPC, correlating with lowered proliferation potential and shortened telomere length. AhCPC characteristics resemble OCPCs, which have a phenotype induced by NS silencing, resulting in cell flattening, senescence, multinucleated cells, decreased S phase progression, diminished expression of stemness markers and up-regulation of p53 and p16. CPC senescence resulting from NS loss is partially p53 dependent and is rescued by concurrent silencing of p53. Mechanistically, NS induction correlates with Pim-1 kinase-mediated stabilization of c-Myc. Engineering OCPCs and AhCPCs to overexpress NS decreases senescent and multinucleated cells, restores morphology, and antagonizes senescence, thereby preserving phenotypic properties of “stemness.” Early cardiac aging with decline in cardiac function, increase in senescence markers p53 and p16, telomere attrition, and accompanied CPC exhaustion is evident in NS+/− mice. CONCLUSIONS Youthful properties and antagonism of

  10. Cardiac Progenitor Cell Commitment is Inhibited by Nuclear Akt Expression

    PubMed Central

    Fischer, Kimberlee M.; Din, Shabana; Gude, Natalie; Konstandin, Mathias H.; Wu, Weitao; Quijada, Pearl; Sussman, Mark A.

    2011-01-01

    Rationale Stem cell therapies to regenerate damaged cardiac tissue represent a novel approach to treat heart disease. However, the majority of adoptively transferred stem cells delivered to damaged myocardium do not survive long enough to impart protective benefits, resulting in modest functional improvements. Strategies to improve survival and proliferation of stem cells show promise for significantly enhancing cardiac function and regeneration. Objective Determine if injected cardiac progenitor cells (CPCs) genetically modified to overexpress nuclear Akt (CPCeA) increase structural and functional benefits to infarcted myocardium relative to control CPCs. Methods and Results CPCeA exhibit significantly increased proliferation and secretion of paracrine factors compared to CPCs. However, CPCeA exhibit impaired capacity for lineage commitment in vitro. Infarcted hearts receiving intramyocardial injection of CPCeA have increased recruitment of endogenous c-kit cells compared to CPCs, but neither population provides long-term functional and structural improvements compared to saline injected controls. Pharmacologic inhibition of Akt alleviated blockade of lineage commitment in CPCeA. Conclusions Although overexpression of nuclear Akt promotes rapid proliferation and secretion of protective paracrine factors, the inability of CPCeA to undergo lineage commitment hinders their capacity to provide functional or structural benefits to infarcted hearts. Despite enhanced recruitment of endogenous CPCs, lack of functional improvement in CPCeA treated hearts demonstrates CPC lineage commitment is essential to the regenerative response. Effective stem cell therapies must promote cellular survival and proliferation without inhibiting lineage commitment. Since CPCeA exhibit remarkable proliferative potential, an inducible system mediating nuclear Akt expression could be useful to augment cell therapy approaches. PMID:21350213

  11. COMPACT BINARY PROGENITORS OF SHORT GAMMA-RAY BURSTS

    SciTech Connect

    Giacomazzo, Bruno; Perna, Rosalba; Rezzolla, Luciano; Troja, Eleonora; Lazzati, Davide

    2013-01-10

    In recent years, detailed observations and accurate numerical simulations have provided support to the idea that mergers of compact binaries containing either two neutron stars (NSs) or an NS and a black hole (BH) may constitute the central engine of short gamma-ray bursts (SGRBs). The merger of such compact binaries is expected to lead to the production of a spinning BH surrounded by an accreting torus. Several mechanisms can extract energy from this system and power the SGRBs. Here we connect observations and numerical simulations of compact binary mergers, and use the current sample of SGRBs with measured energies to constrain the mass of their powering tori. By comparing the masses of the tori with the results of fully general-relativistic simulations, we are able to infer the properties of the binary progenitors that yield SGRBs. By assuming a constant efficiency in converting torus mass into jet energy, {epsilon}{sub jet} = 10%, we find that most of the tori have masses smaller than 0.01 M{sub Sun }, favoring 'high-mass' binary NSs mergers, i.e., binaries with total masses {approx}> 1.5 the maximum mass of an isolated NS. This has important consequences for the gravitational wave signals that may be detected in association with SGRBs, since 'high-mass' systems do not form a long-lived hypermassive NS after the merger. While NS-BH systems cannot be excluded to be the engine of at least some of the SGRBs, the BH would need to have an initial spin of {approx}0.9 or higher.

  12. Transplantation of neural progenitor cells in chronic spinal cord injury.

    PubMed

    Jin, Y; Bouyer, J; Shumsky, J S; Haas, C; Fischer, I

    2016-04-21

    Previous studies demonstrated that neural progenitor cells (NPCs) transplanted into a subacute contusion injury improve motor, sensory, and bladder function. In this study we tested whether transplanted NPCs can also improve functional recovery after chronic spinal cord injury (SCI) alone or in combination with the reduction of glial scar and neurotrophic support. Adult rats received a T10 moderate contusion. Thirteen weeks after the injury they were divided into four groups and received either: 1. Medium (control), 2. NPC transplants, 3. NPC+lentivirus vector expressing chondroitinase, or 4. NPC+lentivirus vectors expressing chondroitinase and neurotrophic factors. During the 8weeks post-transplantation the animals were tested for functional recovery and eventually analyzed by anatomical and immunohistochemical assays. The behavioral tests for motor and sensory function were performed before and after injury, and weekly after transplantation, with some animals also tested for bladder function at the end of the experiment. Transplant survival in the chronic injury model was variable and showed NPCs at the injury site in 60% of the animals in all transplantation groups. The NPC transplants comprised less than 40% of the injury site, without significant anatomical or histological differences among the groups. All groups also showed similar patterns of functional deficits and recovery in the 12weeks after injury and in the 8weeks after transplantation using the Basso, Beattie, and Bresnahan rating score, the grid test, and the Von Frey test for mechanical allodynia. A notable exception was group 4 (NPC together with chondroitinase and neurotrophins), which showed a significant improvement in bladder function. This study underscores the therapeutic challenges facing transplantation strategies in a chronic SCI in which even the inclusion of treatments designed to reduce scarring and increase neurotrophic support produce only modest functional improvements. Further

  13. Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

    PubMed

    Teplan, Vladimír; Mahrová, Andrea; Králová-Lesná, Ivana; Racek, Jaroslav; Valkovský, Ivo; Štollová, Milena

    2015-03-01

    Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 μmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 μmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx. PMID:25576240

  14. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation

    PubMed Central

    Kazemi, Zahra; Bergmayr, Christian; Prchal-Murphy, Michaela; Javaheri, Tahereh; Themanns, Madeleine; Pham, Ha T. T.; Strohmaier, Wolfgang; Sexl, Veronika; Zebedin-Brandl, Eva

    2016-01-01

    Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [3H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the ability of agonist-activated HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The underlying mechanism was explored in cellular migration assays and by blocking C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists tested in combination with forskolin, treprostinil was most efficacious in raising intracellular cAMP levels in murine and human HPSCs. Injection of murine and human HSPCs, which had been pretreated with treprostinil and forskolin, enhanced survival of lethally irradiated recipient mice. Survival was further improved if recipient mice were subcutaneously administered treprostinil (0.15 mg kg−1 8 h−1) for 10 days. This regimen also reduced the number of HSPCs required to rescue lethally irradiated mice. Enhanced survival of recipient mice was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs. Treprostinil stimulates the engraftment of human and murine hematopoietic stem cells without impairing their capacity for self-renewal. The investigated dose range corresponds to the dose approved for human use. Hence, these findings may be readily translated into a clinical application. PMID:26989084

  15. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation.

    PubMed

    Kazemi, Zahra; Bergmayr, Christian; Prchal-Murphy, Michaela; Javaheri, Tahereh; Themanns, Madeleine; Pham, Ha T T; Strohmaier, Wolfgang; Sexl, Veronika; Freissmuth, Michael; Zebedin-Brandl, Eva

    2016-06-01

    Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [(3)H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the ability of agonist-activated HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The underlying mechanism was explored in cellular migration assays and by blocking C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists tested in combination with forskolin, treprostinil was most efficacious in raising intracellular cAMP levels in murine and human HPSCs. Injection of murine and human HSPCs, which had been pretreated with treprostinil and forskolin, enhanced survival of lethally irradiated recipient mice. Survival was further improved if recipient mice were subcutaneously administered treprostinil (0.15 mg kg(-1) 8 h(-1)) for 10 days. This regimen also reduced the number of HSPCs required to rescue lethally irradiated mice. Enhanced survival of recipient mice was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs. Treprostinil stimulates the engraftment of human and murine hematopoietic stem cells without impairing their capacity for self-renewal. The investigated dose range corresponds to the dose approved for human use. Hence, these findings may be readily translated into a clinical application. PMID:26989084

  16. Characterization of Endothelial Progenitor Cell Interactions with Human Tropoelastin

    PubMed Central

    Yu, Young; Wise, Steven G.; Michael, Praveesuda L.; Bax, Daniel V.; Yuen, Gloria S. C.; Hiob, Matti A.; Yeo, Giselle C.; Filipe, Elysse C.; Dunn, Louise L.; Chan, Kim H.; Hajian, Hamid; Celermajer, David S.; Weiss, Anthony S.; Ng, Martin K. C.

    2015-01-01

    The deployment of endovascular implants such as stents in the treatment of cardiovascular disease damages the vascular endothelium, increasing the risk of thrombosis and promoting neointimal hyperplasia. The rapid restoration of a functional endothelium is known to reduce these complications. Circulating endothelial progenitor cells (EPCs) are increasingly recognized as important contributors to device re-endothelialization. Extracellular matrix proteins prominent in the vessel wall may enhance EPC-directed re-endothelialization. We examined attachment, spreading and proliferation on recombinant human tropoelastin (rhTE) and investigated the mechanism and site of interaction. EPCs attached and spread on rhTE in a dose dependent manner, reaching a maximal level of 56±3% and 54±3%, respectively. EPC proliferation on rhTE was comparable to vitronectin, fibronectin and collagen. EDTA, but not heparan sulfate or lactose, reduced EPC attachment by 81±3%, while full attachment was recovered after add-back of manganese, inferring a classical integrin-mediated interaction. Integrin αVβ3 blocking antibodies decreased EPC adhesion and spreading on rhTE by 39±3% and 56±10% respectively, demonstrating a large contribution from this specific integrin. Attachment of EPCs on N-terminal rhTE constructs N25 and N18 accounted for most of this interaction, accompanied by comparable spreading. In contrast, attachment and spreading on N10 was negligible. αVβ3 blocking antibodies reduced EPC spreading on both N25 and N18 by 45±4% and 42±14%, respectively. In conclusion, rhTE supports EPC binding via an integrin mechanism involving αVβ3. N25 and N18, but not N10 constructs of rhTE contribute to EPC binding. The regulation of EPC activity by rhTE may have implications for modulation of the vascular biocompatibility of endovascular implants. PMID:26115013

  17. Characterization of Endothelial Progenitor Cell Interactions with Human Tropoelastin.

    PubMed

    Yu, Young; Wise, Steven G; Michael, Praveesuda L; Bax, Daniel V; Yuen, Gloria S C; Hiob, Matti A; Yeo, Giselle C; Filipe, Elysse C; Dunn, Louise L; Chan, Kim H; Hajian, Hamid; Celermajer, David S; Weiss, Anthony S; Ng, Martin K C

    2015-01-01

    The deployment of endovascular implants such as stents in the treatment of cardiovascular disease damages the vascular endothelium, increasing the risk of thrombosis and promoting neointimal hyperplasia. The rapid restoration of a functional endothelium is known to reduce these complications. Circulating endothelial progenitor cells (EPCs) are increasingly recognized as important contributors to device re-endothelialization. Extracellular matrix proteins prominent in the vessel wall may enhance EPC-directed re-endothelialization. We examined attachment, spreading and proliferation on recombinant human tropoelastin (rhTE) and investigated the mechanism and site of interaction. EPCs attached and spread on rhTE in a dose dependent manner, reaching a maximal level of 56±3% and 54±3%, respectively. EPC proliferation on rhTE was comparable to vitronectin, fibronectin and collagen. EDTA, but not heparan sulfate or lactose, reduced EPC attachment by 81±3%, while full attachment was recovered after add-back of manganese, inferring a classical integrin-mediated interaction. Integrin αVβ3 blocking antibodies decreased EPC adhesion and spreading on rhTE by 39±3% and 56±10% respectively, demonstrating a large contribution from this specific integrin. Attachment of EPCs on N-terminal rhTE constructs N25 and N18 accounted for most of this interaction, accompanied by comparable spreading. In contrast, attachment and spreading on N10 was negligible. αVβ3 blocking antibodies reduced EPC spreading on both N25 and N18 by 45±4% and 42±14%, respectively. In conclusion, rhTE supports EPC binding via an integrin mechanism involving αVβ3. N25 and N18, but not N10 constructs of rhTE contribute to EPC binding. The regulation of EPC activity by rhTE may have implications for modulation of the vascular biocompatibility of endovascular implants. PMID:26115013

  18. The progenitors of extended emission gamma-ray bursts

    NASA Astrophysics Data System (ADS)

    Gompertz, B. P.

    2015-06-01

    Gamma-ray bursts (GRBs) are the most luminous transient events in the Universe, and as such are associated with some of the most extreme processes in nature. They come in two types: long and short, nominally separated either side of a two second divide in gamma-ray emission duration. The short class (those with durations of less than two seconds) are believed to be due to the merger of two compact objects, most likely neutron stars. Within this population, a small subsection exhibit an apparent extra high-energy emission feature, which rises to prominence several seconds after the initial emission event. These are the extended emission (EE) bursts. This thesis investigates the progenitors of the EE sample, including what drives them, and where they fit in the broader context of short GRBs. The science chapters outline a rigorous test of the magnetar model, in which the compact object merger results in a massive, rapidly-rotating neutron star with an extremely strong magnetic field. The motivation for this central engine is the late-time plateaux seen in some short and EE GRBs, which can be interpreted as energy injection from a long-lived central engine, in this case from the magnetar as it loses angular momentum along open field lines. Chapter 2 addresses the energy budget of such a system, including whether the EE component is consistent with the rotational energy reservoir of a millisecond neutron star, and the implications the model has for the physical properties of the underlying magnetar. Chapter 3 proposes a potential mechanism by which EE may arise, and how both classes may be born within the framework of a single central engine. Chapter 4 addresses the broadband signature of both short and EE GRBs, and provides some observational tests that can be used to either support or contradict the model.

  19. Compact Binary Progenitors of Short Gamma-Ray Bursts

    NASA Technical Reports Server (NTRS)

    Giacomazzo, Bruno; Perna, Rosalba; Rezzolla, Luciano; Troja, Eleonora; Lazzati, Davide

    2013-01-01

    In recent years, detailed observations and accurate numerical simulations have provided support to the idea that mergers of compact binaries containing either two neutron stars (NSs) or an NS and a black hole (BH) may constitute the central engine of short gamma-ray bursts (SGRBs). The merger of such compact binaries is expected to lead to the production of a spinning BH surrounded by an accreting torus. Several mechanisms can extract energy from this system and power the SGRBs. Here we connect observations and numerical simulations of compact binary mergers, and use the current sample of SGRBs with measured energies to constrain the mass of their powering tori. By comparing the masses of the tori with the results of fully general-relativistic simulations, we are able to infer the properties of the binary progenitors that yield SGRBs. By assuming a constant efficiency in converting torus mass into jet energy epsilon(sub jet) = 10%, we find that most of the tori have masses smaller than 0.01 Solar M, favoring "high-mass" binary NSs mergers, i.e., binaries with total masses approx >1.5 the maximum mass of an isolated NS. This has important consequences for the gravitational wave signals that may be detected in association with SGRBs, since "high-mass" systems do not form a long-lived hypermassive NS after the merger. While NS-BH systems cannot be excluded to be the engine of at least some of the SGRBs, the BH would need to have an initial spin of approx. 0.9 or higher.

  20. Retinal Endothelial Cell Apoptosis Stimulates Recruitment of Endothelial Progenitor Cells

    PubMed Central

    Bhatwadekar, Ashay D.; Glenn, Josephine V.; Curtis, Tim M.; Grant, Maria B.; Stitt, Alan W.; Gardiner, Tom A.

    2013-01-01

    Purpose Bone marrow–derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair. Methods Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed. Results Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05– 0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-α when compared to control medium; SDF-1 remained unchanged. Conclusions The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment. PMID:19474402

  1. S-phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex.

    PubMed

    Turrero García, Miguel; Chang, YoonJeung; Arai, Yoko; Huttner, Wieland B

    2016-02-15

    The evolutionary expansion of the neocortex primarily reflects increases in abundance and proliferative capacity of cortical progenitors and in the length of the neurogenic period during development. Cell cycle parameters of neocortical progenitors are an important determinant of cortical development. The ferret (Mustela putorius furo), a gyrencephalic mammal, has gained increasing importance as a model for studying corticogenesis. Here, we have studied the abundance, proliferation, and cell cycle parameters of different neural progenitor types, defined by their differential expression of the transcription factors Pax6 and Tbr2, in the various germinal zones of developing ferret neocortex. We focused our analyses on postnatal day 1, a late stage of cortical neurogenesis when upper-layer neurons are produced. Based on cumulative 5-ethynyl-2'-deoxyuridine (EdU) labeling as well as Ki67 and proliferating cell nuclear antigen (PCNA) immunofluorescence, we determined the duration of the various cell cycle phases of the different neocortical progenitor subpopulations. Ferret neocortical progenitors were found to exhibit longer cell cycles than those of rodents and little variation in the duration of G1 among distinct progenitor types, also in contrast to rodents. Remarkably, the main difference in cell cycle parameters among the various progenitor types was the duration of S-phase, which became shorter as progenitors progressively changed transcription factor expression from patterns characteristic of self-renewal to those of neuron production. Hence, S-phase duration emerges as major target of cell cycle regulation in cortical progenitors of this gyrencephalic mammal. PMID:25963823

  2. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    PubMed Central

    2012-01-01

    Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains

  3. THE MASSIVE PROGENITOR OF THE POSSIBLE TYPE II-LINEAR SUPERNOVA 2009hd IN MESSIER 66

    SciTech Connect

    Elias-Rosa, Nancy; Van Dyk, Schuyler D.; Mauerhan, Jon C.; Li, Weidong; Silverman, Jeffrey M.; Ganeshalingam, Mohan; Filippenko, Alexei V.; Smith, Nathan; Foley, Ryan J.; Berger, Edo; Jha, Saurabh; Beckman, John E.; Cuillandre, Jean-Charles

    2011-11-20

    We present early- and late-time photometric and spectroscopic observations of supernova (SN) 2009hd in the nearby spiral galaxy NGC 3627 (M66). This SN is one of the closest to us in recent years and provides an uncommon opportunity to observe and study the nature of SNe. However, the object was heavily obscured by dust, rendering it unusually faint in the optical given its proximity. We find that the observed properties of SN 2009hd support its classification as a possible Type II-Linear SN (SN II-L), a relatively rare subclass of core-collapse SNe. High-precision relative astrometry has been employed to attempt to identify an SN progenitor candidate, based on a pixel-by-pixel comparison between Hubble Space Telescope (HST) F555W and F814W images of the SN site prior to explosion and at late times. A progenitor candidate is identified in the F814W images only; this object is undetected in F555W. Significant uncertainty exists in the astrometry, such that we cannot definitively identify this object as the SN progenitor. Via insertion of artificial stars into the pre-SN HST images, we are able to constrain the progenitor's properties to those of a possible supergiant, with intrinsic absolute magnitude M {sup 0}{sub F555W} {approx}> -7.6 mag and intrinsic color (V - I){sup 0} {approx}> 0.99 mag. The magnitude and color limits are consistent with a luminous red supergiant (RSG); however, they also allow for the possibility that the star could have been more yellow than red. From a comparison with theoretical massive-star evolutionary tracks which include rotation and pulsationally enhanced mass loss, we can place a conservative upper limit on the initial mass for the progenitor of M{sub ini} {approx}< 20 M{sub Sun }. If the actual mass of the progenitor is near the upper range allowed by our derived mass limit, then it would be consistent with that for the identified progenitors of the SN II-L 2009kr and the high-luminosity SN II-Plateau (II-P) 2008cn. The progenitors

  4. Development and specification of cerebellar stem and progenitor cells in zebrafish: from embryo to adult

    PubMed Central

    2013-01-01

    Background Teleost fish display widespread post-embryonic neurogenesis originating from many different proliferative niches that are distributed along the brain axis. During the development of the central nervous system (CNS) different cell types are produced in a strict temporal order from increasingly committed progenitors. However, it is not known whether diverse neural stem and progenitor cell types with restricted potential or stem cells with broad potential are maintained in the teleost fish brain. Results To study the diversity and output of neural stem and progenitor cell populations in the zebrafish brain the cerebellum was used as a model brain region, because of its well-known architecture and development. Transgenic zebrafish lines, in vivo imaging and molecular markers were used to follow and quantify how the proliferative activity and output of cerebellar progenitor populations progress. This analysis revealed that the proliferative activity and progenitor marker expression declines in juvenile zebrafish before they reach sexual maturity. Furthermore, this correlated with the diminished repertoire of cell types produced in the adult. The stem and progenitor cells derived from the upper rhombic lip were maintained into adulthood and they actively produced granule cells. Ventricular zone derived progenitor cells were largely quiescent in the adult cerebellum and produced a very limited number of glia and inhibitory inter-neurons. No Purkinje or Eurydendroid cells were produced in fish older than 3 months. This suggests that cerebellar cell types are produced in a strict temporal order from distinct pools of increasingly committed stem and progenitor cells. Conclusions Our results in the zebrafish cerebellum show that neural stem and progenitor cell types are specified and they produce distinct cell lineages and sub-types of brain cells. We propose that only specific subtypes of brain cells are continuously produced throughout life in the teleost fish

  5. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

    PubMed Central

    Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A.; Montrose, Marshall H.

    2015-01-01

    Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration. PMID:26597788

  6. Analysis of eosinophils and myeloid progenitor responses to modified forms of MPIF-2.

    PubMed

    Grzegorzewski, K J; Yao, X T; Kreider, B; Olsen, H S; Morris, T S; Zhang, L; Sanyal, I; Nardelli, B; Zukauskas, D; Brewer, L; Bong, G W; Kim, Y; Garotta, G; Salcedo, T W

    2001-02-21

    Myeloid progenitor inhibitory factor (MPIF)-2 is a beta-chemokine with select and potent activities on eosinophils and myeloid progenitors. In the beta-chemokine family, biological activity is modulated by differential processing of the amino-terminus. Here, for MPIF-2, we describe the biological activities of NH(2)-terminal deletion mutants and compare regions necessary for eosinophil and myeloid progenitor activities. Five MPIF-2 proteins with deletions at the amino-terminus were produced in Escherichia coli and assayed for calcium mobilization, chemotaxis and receptor binding activities on eosinophils, and for their ability to inhibit colony formation of human myeloid bone marrow progenitors. For eosinophils, deletion of the first two amino acids did not markedly alter activity, while subsequent truncations result in a complete loss of activity. One of the MPIF-2 mutants, MPIF-2 (P30-R99) was converted from an agonist to an antagonist of eotaxin, MPIF-2 and MCP-4 functional responses in eosinophil calcium flux and chemotaxis assays. Surprisingly, while displaying a complete loss of agonist activity toward eosinophils, MPIF-2 (P30-R99) retains ability to inhibit human bone marrow myeloid progenitor cell colony formation. In addition, processing at the amino terminus of MPIF-2 in vivo, may result in a chemokine with altered biological activities. PMID:11237428

  7. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells.

    PubMed

    Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S; Felldin, Ulrika; He, Xiaobing; Nichane, Massimo; Yang, Henry; Bu, Lei; Li, Ronald A; Lim, Bing; Chien, Kenneth R

    2016-01-01

    Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1(+) vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo. PMID:26952167

  8. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.

    PubMed

    Beyaz, Semir; Mana, Miyeko D; Roper, Jatin; Kedrin, Dmitriy; Saadatpour, Assieh; Hong, Sue-Jean; Bauer-Rowe, Khristian E; Xifaras, Michael E; Akkad, Adam; Arias, Erika; Pinello, Luca; Katz, Yarden; Shinagare, Shweta; Abu-Remaileh, Monther; Mihaylova, Maria M; Lamming, Dudley W; Dogum, Rizkullah; Guo, Guoji; Bell, George W; Selig, Martin; Nielsen, G Petur; Gupta, Nitin; Ferrone, Cristina R; Deshpande, Vikram; Yuan, Guo-Cheng; Orkin, Stuart H; Sabatini, David M; Yilmaz, Ömer H

    2016-03-01

    Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-δ) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-δ recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-δ-dependent manner. Notably, HFD- and agonist-activated PPAR-δ signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-δ signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-δ activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours. PMID:26935695

  9. Calorie Restriction Alleviates Age-Related Decrease in Neural Progenitor Cell Division in the Aging Brain

    PubMed Central

    Park, June-Hee; Glass, Zachary; Sayed, Kasim; Michurina, Tatyana V.; Lazutkin, Alexander; Mineyeva, Olga; Velmeshev, Dmitry; Ward, Walter F.; Richardson, Arlan; Enikolopov, Grigori

    2013-01-01

    Production of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age-related cognitive deficits. Restriction of calorie intake and prolonged treatment with rapamycin have been shown to extend the lifespan of animals and delay the onset of age-related decline in tissue and organ function. Using a reporter line in which neural stem and progenitor cells are marked by the expression of GFP, we examined the effect of prolonged exposure to calorie restriction (CR) or rapamycin on hippocampal neural stem and progenitor cell proliferation in aging mice. We show that CR increases the number of dividing cells in the dentate gyrus (DG) of female mice. The majority of these cells corresponded to Nestin-GFP-expressing neural stem or progenitor cells; however, this increased proliferative activity of stem and progenitor cells did not result in a significant increase in the number of doublecortin-positive newborn neurons. Our results suggest that restricted calorie intake may increase the number of divisions that neural stem and progenitor cells undergo in the aging brain of females. PMID:23773068

  10. Stellar Forensics IV: A post-explosion view of the progenitors of core-collapse supernovae

    NASA Astrophysics Data System (ADS)

    Maund, Justyn

    2012-10-01

    Recent studies have used high spatial resolution HST observations of supernova {SN} sites to directly identify the progenitors of core-collapse SNe on pre-explosion images. These studies have set constraints about the nature of massive stars and their evolution just prior to their explosion as SNe. Now, at late-times when the SNe have faded sufficiently, it is possible to return to the sites of these core-collapse supernovae to search for clues about the nature of their progenitors.We request time to conduct deep, late-time, high-resolution imaging with WFC3 UVIS of the site of the core-collapse SN 2009hd. We aim to: 1} Confirm our original identification, made in pre-explosion images, by confirming that the progenitor is now missing; 2} Apply image subtraction techniques for the pre-explosion images with this late-time imaging to determine accurate photometry of the progenitor to constrain its temperature and luminosity; and 3} use the stellar population in the immediate vicinity of the SN to determine the reddening and extinction that affected the progenitor. HST provides the unique combination of high-resolution optical/IR imaging at very faint magnitudes that will facilitate this study.

  11. Identification of proliferative progenitors associated with prominent postnatal growth of the pons

    PubMed Central

    Lindquist, Robert A.; Guinto, Cristina D.; Rodas-Rodriguez, Jose L.; Fuentealba, Luis C.; Tate, Matthew C.; Rowitch, David H.; Alvarez-Buylla, Arturo

    2016-01-01

    The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0–4 (P0–P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2+Olig2+, but by P8 a Sox2− subpopulation emerges, suggesting a lineage progression from Sox2+ ‘early' to Sox2− ‘late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2–P3 Sox2+ progenitors. These results demonstrate the importance of postnatal Sox2+Olig2+ progenitors in pontine growth and oligodendrogenesis. PMID:27188978

  12. Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors

    PubMed Central

    Sidney, Laura E; Branch, Matthew J; Dunphy, Siobhán E; Dua, Harminder S; Hopkinson, Andrew

    2014-01-01

    CD34 is a transmembrane phosphoglycoprotein, first identified on hematopoietic stem and progenitor cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells, and it is a common misconception that CD34-positive (CD34+) cells in nonhematopoietic samples represent hematopoietic contamination. The prevailing school of thought states that multipotent mesenchymal stromal cells (MSC) do not express CD34. However, strong evidence demonstrates CD34 is expressed not only by MSC but by a multitude of other nonhematopoietic cell types including muscle satellite cells, corneal keratocytes, interstitial cells, epithelial progenitors, and vascular endothelial progenitors. In many cases, the CD34+ cells represent a small proportion of the total cell population and also indicate a distinct subset of cells with enhanced progenitor activity. Herein, we explore common traits between cells that express CD34, including associated markers, morphology and differentiation potential. We endeavor to highlight key similarities between CD34+ cells, with a focus on progenitor activity. A common function of CD34 has yet to be elucidated, but by analyzing and understanding links between CD34+ cells, we hope to be able to offer an insight into the overlapping properties of cells that express CD34. Stem Cells 2014;32:1380–1389 PMID:24497003

  13. c-Myc–mediated control of cell fate in megakaryocyte-erythrocyte progenitors

    PubMed Central

    Guo, Yinshi; Niu, Chao; Breslin, Peter; Tang, Minghui; Zhang, Shubin; Wei, Wei; Kini, Ameet R.; Paner, Gladell P.; Alkan, Serhan; Morris, Stephan W.; Diaz, Manuel; Stiff, Patrick J.

    2009-01-01

    It has been found that c-Myc protein plays a critical role in controlling self-renewal versus differentiation in hematopoietic stem cells. We report that c-Myc also controls the fate of megakaryocyte-erythrocyte progenitors through regulating the differentiation of erythroid and megakaryocytic progenitors. In addition to the significant reduction of granulocytes/macrophages and B and T lymphocytes because of the reduction of their corresponding progenitors, we found significantly increased numbers of megakaryocytic progenitors and mature megakaryocytes in bone marrow and spleens of c-Myc-knockout (c-Myc−/−) mice. Differentiation of erythrocytes was blocked at the erythroid progenitor stage. This increased megakaryocytopoiesis is a cell-intrinsic defect of c-Myc-mutant hematopoietic stem cells, as shown by transplantation studies. Furthermore, we found that c-Myc is required for polyploidy formation but not for cytoplasmic maturation of megakaryocytes. Megakaryocytes from c-Myc−/− mice are significantly smaller in size and lower in ploidy than those of control mice; however, because of the dramatic increase in megakaryocyte number, although fewer platelets are produced by each megakaryocyte, a greater than 3-fold increase in platelet number was consistently observed in c-Myc−/− mice. Thus, c-Myc−/− mice develop a syndrome of severe thrombocytosis-anemia-leukopenia because of significant increases in megakaryocytopoiesis and concomitant blockage of erythrocyte differentiation and reductions in myelolymphopoiesis. PMID:19372257

  14. Metallicity dependence of Type Ib/c and IIb supernova progenitors in binary systems

    NASA Astrophysics Data System (ADS)

    Yoon, Sung-CHul

    2015-08-01

    Type Ib/c supernovae (SNe Ib/c) are characterized by the lack of prominent hydrogen lines in the spectra, implying that their progenitors have lost most of their hydrogen envelopes by the time of the iron core collapse. Binary interactions provide an important evolutionary chanel for SNe Ib/c, and recent observations indicate that the inferred ejecta masses of SNe Ibc are more consistent with the prediction of the binary scenario than that of the single star scenario that invokes mass loss as the key evolutionary factor for SNe Ib/c progenitors. So far, theoretical predictions on the detailed properties of SNe Ib/c progenitors in binary systems have been made mostly with models using solar metallicity. However, unlike the single star scenario, where SNe Ib/c are expected only for sufficiently high metallicity, hydrogen-deficent SN progenitors can be produced via binary interactions at any metallicity. In this talk, I will discuss theoretical predictions on the metallicity dependence of the SNe Ib/c progenitor structure, based on evolutionary models of massive binary stars. Sepefically, I will address how the ejecta masses of SNe Ib and Ic and the ratio of SN Ib/c to SN IIb as well as SN Ib to SN Ic would systematically change as a function of metallicity, and which new types of SNe are expected in binary systems at low metallicity.

  15. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

    PubMed

    Gargett, C E; Schwab, K E; Brosens, J J; Puttemans, P; Benagiano, G; Brosens, I

    2014-07-01

    The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition. PMID:24674992

  16. Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development.

    PubMed

    Hu, Yan; Li, Minghong; Göthert, Joachim R; Gomez, R Ariel; Sequeira-Lopez, Maria Luisa S

    2016-07-01

    The close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1(+) progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein-coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1(+) progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development. PMID:26534925

  17. Stellar Forensics V: A post-explosion view of the progenitor of SN 2011dh

    NASA Astrophysics Data System (ADS)

    Maund, Justyn

    2013-10-01

    Recent studies have used high spatial resolution HST observations of supernova (SN) sites to directly identify the progenitors of core-collapse SNe on pre-explosion images. These studies have set constraints about the nature of massive stars and their evolution just prior to their explosion as SNe. Now, at late-times when the SNe have faded sufficiently, it is possible to return to the sites of these core-collapse supernovae to search for clues about the nature of their progenitors.We request time to conduct deep, late-time, high-resolution imaging with WFC3 UVIS and ACS WFC of the site of the Type IIb supernova 2011dh. The nature of the observed yellow supergiant progenitor conflicts with the predictions of stellar evolution models and our understanding of the optical and radio light curves of the subsequent supernova.We aim to: 1) Confirm our original identification, made in pre-explosion images, by confirming that the yellow supergiant is now missing; 2) Apply image subtraction techniques for the pre-explosion images with this late-time imaging to determine accurate photometry of the progenitor to constrain its temperature and luminosity; 3) conduct a deep search for the hypothesised hot binary companion; and 4) use the stellar population in the immediate vicinity of the SN to determine the reddening and extinction that affected the progenitor. HST provides the unique combination of high-resolution UV/optical imaging at very faint magnitudes that will facilitate this study.

  18. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells

    PubMed Central

    Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C.; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S.; Felldin, Ulrika; He, Xiaobing; Nichane, Massimo; Yang, Henry; Bu, Lei; Li, Ronald A.; Lim, Bing; Chien, Kenneth R.

    2016-01-01

    Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human–mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1+ vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo. PMID:26952167

  19. Disappearance of the Progenitor of Supernova iPTF13bvn

    NASA Astrophysics Data System (ADS)

    Folatelli, Gastón; Van Dyk, Schuyler D.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Bersten, Melina C.; Nomoto, Ken’ichi; Pignata, Giuliano; Hamuy, Mario; Quimby, Robert M.; Zheng, WeiKang; Filippenko, Alexei V.; Clubb, Kelsey I.; Smith, Nathan; Elias-Rosa, Nancy; Foley, Ryan J.; Miller, Adam A.

    2016-07-01

    Supernova (SN) iPTF13bvn in NGC 5806 was the first Type Ib SN to have been tentatively associated with a progenitor in pre-explosion images. We performed deep ultraviolet (UV) and optical Hubble Space Telescope observations of the SN site ˜740 days after explosion. We detect an object in the optical bands that is fainter than the pre-explosion object. This dimming is likely not produced by dust absorption in the ejecta; thus, our finding confirms the connection of the progenitor candidate with the SN. The object in our data is likely dominated by the fading SN, implying that the pre-SN flux is mostly due to the progenitor. We compare our revised pre-SN photometry with previously proposed models. Although binary progenitors are favored, models need to be refined. In particular, to comply with our deep UV detection limit, any companion star must be less luminous than a late-O star or substantially obscured by newly formed dust. A definitive progenitor characterization will require further observations to disentangle the contribution of a much fainter SN and its environment.

  20. The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche

    PubMed Central

    Benmimoun, Billel; Polesello, Cédric; Haenlin, Marc; Waltzer, Lucas

    2015-01-01

    The maintenance of stem or progenitor cell fate relies on intrinsic factors as well as local cues from the cellular microenvironment and systemic signaling. In the lymph gland, an hematopoietic organ in Drosophila larva, a group of cells called the Posterior Signaling Centre (PSC), whose specification depends on the EBF transcription factor Collier (Col) and the HOX factor Antennapedia (Antp), has been proposed to form a niche required to maintain the pool of hematopoietic progenitors (prohemocytes). In contrast with this model, we show here that genetic ablation of the PSC does not cause an increase in blood cell differentiation or a loss of blood cell progenitors. Furthermore, although both col and Antp mutant larvae are devoid of PSC, the massive prohemocyte differentiation observed in col mutant is not phenocopied in Antp mutant. Interestingly, beside its expression in the PSC, Col is also expressed at low levels in prohemocytes and we show that this expression persists in PSC-ablated and Antp mutant larvae. Moreover, targeted knockdown and rescue experiments indicate that Col expression is required in the prohemocytes to prevent their differentiation. Together, our findings show that the PSC is dispensable for blood cell progenitor maintenance and reveal the key role of the conserved transcription factor Col as an intrinsic regulator of hematopoietic progenitor fate. PMID:26150488

  1. Heterogeneity and Bipotency of Astroglial-Like Cerebellar Progenitors along the Interneuron and Glial Lineages.

    PubMed

    Parmigiani, Elena; Leto, Ketty; Rolando, Chiara; Figueres-Oñate, María; López-Mascaraque, Laura; Buffo, Annalisa; Rossi, Ferdinando

    2015-05-13

    Cerebellar GABAergic interneurons in mouse comprise multiple subsets of morphologically and neurochemically distinct phenotypes located at strategic nodes of cerebellar local circuits. These cells are produced by common progenitors deriving from the ventricular epithelium during embryogenesis and from the prospective white matter (PWM) during postnatal development. However, it is not clear whether these progenitors are also shared by other cerebellar lineages and whether germinative sites different from the PWM originate inhibitory interneurons. Indeed, the postnatal cerebellum hosts another germinal site along the Purkinje cell layer (PCL), in which Bergmann glia are generated up to first the postnatal weeks, which was proposed to be neurogenic. Both PCL and PWM comprise precursors displaying traits of juvenile astroglia and neural stem cell markers. First, we examine the proliferative and fate potential of these niches, showing that different proliferative dynamics regulate progenitor amplification at these sites. In addition, PCL and PWM differ in the generated progeny. GABAergic interneurons are produced exclusively by PWM astroglial-like progenitors, whereas PCL precursors produce only astrocytes. Finally, through in vitro, ex vivo, and in vivo clonal analyses we provide evidence that the postnatal PWM hosts a bipotent progenitor that gives rise to both interneurons and white matter astrocytes. PMID:25972168

  2. In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Pancreatic Progenitors

    PubMed Central

    Chmielowiec, Jolanta; Borowiak, Malgorzata

    2014-01-01

    Recent progress in understanding stem cell biology has been remarkable, especially in deciphering signals that support differentiation towards tissue-specific lineages. This achievement positions us firmly at the beginning of an era of patient-specific regenerative medicine and human disease modeling. It will be necessary to equip the progress in this era with a reliable source of self-renewing progenitor cells that differentiate into functional target cells. The generation of pancreatic progenitors that mature in vivo into functional beta-cells has raised the hope for new therapeutic options in diabetes, but key challenges still remain including the production of sufficient numbers of cells for research and transplantation. Recent approaches to this problem have shown that the presence of organ- and stage-specific mesenchyme improves the generation of progenitors, from endoderm to endocrine cells. Alternatively, utilization of three-dimensional culture may improve the efficiency and yield of directed differentiation. Here, we review the current knowledge of pancreatic directed differentiation and ex vivo expansion of pancreatic progenitors, including recent advances in differentiation strategies for the generation of pancreatic progenitors, and we discuss persistent challenges which will need to be overcome before personalized cell-based therapy becomes a practical strategy. PMID:25148365

  3. Spatiotemporal analyses of neural lineages after embryonic and postnatal progenitor targeting combining different reporters

    PubMed Central

    Figueres-Oñate, Maria; García-Marqués, Jorge; Pedraza, Maria; De Carlos, Juan Andrés; López-Mascaraque, Laura

    2015-01-01

    Genetic lineage tracing with electroporation is one of the most powerful techniques to target neural progenitor cells and their progeny. However, the spatiotemporal relationship between neural progenitors and their final phenotype remain poorly understood. One critical factor to analyze the cell fate of progeny is reporter integration into the genome of transfected cells. To address this issue, we performed postnatal and in utero co-electroporations of different fluorescent reporters to label, in both cerebral cortex and olfactory bulb, the progeny of subventricular zone neural progenitors. By comparing fluorescent reporter expression in the adult cell progeny, we show a differential expression pattern within the same cell lineage, depending on electroporation stage and cell identity. Further, while neuronal lineages arise from many progenitors in proliferative zones after few divisions, glial lineages come from fewer progenitors that accomplish many cell divisions. Together, these data provide a useful guide to select a strategy to track the cell fate of a specific cell population and to address whether a different proliferative origin might be correlated with functional heterogeneity. PMID:25852461

  4. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    PubMed

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. PMID:24345734

  5. Hypothyroidism Impairs Human Stem Cell-Derived Pancreatic Progenitor Cell Maturation in Mice.

    PubMed

    Bruin, Jennifer E; Saber, Nelly; O'Dwyer, Shannon; Fox, Jessica K; Mojibian, Majid; Arora, Payal; Rezania, Alireza; Kieffer, Timothy J

    2016-05-01

    Pancreatic progenitors derived from human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating diabetes and are currently being tested in clinical trials. Yet, how the milieu of pancreatic progenitor cells, including exposure to different factors after transplant, may influence their maturation remains unclear. Here, we examined the effect of thyroid dysregulation on the development of hESC-derived progenitor cells in vivo. Hypothyroidism was generated in SCID-beige mice using an iodine-deficient diet containing 0.15% propyl-2-thiouracil, and hyperthyroidism was generated by addition of L-thyroxine (T4) to drinking water. All mice received macroencapsulated hESC-derived progenitor cells, and thyroid dysfunction was maintained for the duration of the study ("chronic") or for 4 weeks posttransplant ("acute"). Acute hyperthyroidism did not affect graft function, but acute hypothyroidism transiently impaired human C-peptide secretion at 16 weeks posttransplant. Chronic hypothyroidism resulted in severely blunted basal human C-peptide secretion, impaired glucose-stimulated insulin secretion, and elevated plasma glucagon levels. Grafts from chronic hypothyroid mice contained fewer β-cells, heterogenous MAFA expression, and increased glucagon(+) and ghrelin(+) cells compared to grafts from euthyroid mice. Taken together, these data suggest that long-term thyroid hormone deficiency may drive the differentiation of human pancreatic progenitor cells toward α- and ε-cell lineages at the expense of β-cell formation. PMID:26740603

  6. Nucleic Acid Encoding A Lectin-Derived Progenitor Cell Preservation Factor

    DOEpatents

    Colucci, M. Gabriella; Chrispeels, Maarten J.; Moore, Jeffrey G.

    2001-10-30

    The invention relates to an isolated nucleic acid molecule that encodes a protein that is effective to preserve progenitor cells, such as hematopoietic progenitor cells. The nucleic acid comprises a sequence defined by SEQ ID NO:1, a homolog thereof, or a fragment thereof. The encoded protein has an amino acid sequence that comprises a sequence defined by SEQ ID NO:2, a homolog thereof, or a fragment thereof that contains an amino acid sequence TNNVLQVT. Methods of using the encoded protein for preserving progenitor cells in vitro, ex vivo, and in vivo are also described. The invention, therefore, include methods such as myeloablation therapies for cancer treatment wherein myeloid reconstitution is facilitated by means of the specified protein. Other therapeutic utilities are also enabled through the invention, for example, expanding progenitor cell populations ex vivo to increase chances of engraftation, improving conditions for transporting and storing progenitor cells, and facilitating gene therapy to treat and cure a broad range of life-threatening hematologic diseases.

  7. Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors

    PubMed Central

    Hedlund, Eva; Belnoue, Laure; Theofilopoulos, Spyridon; Salto, Carmen; Bye, Chris; Parish, Clare; Deng, Qiaolin; Kadkhodaei, Banafsheh; Ericson, Johan; Arenas, Ernest; Perlmann, Thomas; Simon, András

    2016-01-01

    Degeneration of dopamine neurons in the midbrain causes symptoms of the movement disorder, Parkinson disease. Dopamine neurons are generated from proliferating progenitor cells localized in the embryonic ventral midbrain. However, it remains unclear for how long cells with dopamine progenitor character are retained and if there is any potential for reactivation of such cells after cessation of normal dopamine neurogenesis. We show here that cells expressing Lmx1a and other progenitor markers remain in the midbrain aqueductal zone beyond the major dopamine neurogenic period. These cells express dopamine receptors, are located in regions heavily innervated by midbrain dopamine fibres and their proliferation can be stimulated by antagonizing dopamine receptors, ultimately leading to increased neurogenesis in vivo. Furthermore, treatment with dopamine receptor antagonists enhances neurogenesis in vitro, both from embryonic midbrain progenitors as well as from embryonic stem cells. Altogether our results indicate a potential for reactivation of resident midbrain cells with dopamine progenitor potential beyond the normal period of dopamine neurogenesis. PMID:27246266

  8. Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly

    PubMed Central

    Shimada, Mikio; Matsuzaki, Fumio; Kato, Akihiro; Kobayashi, Junya; Matsumoto, Tomohiro; Komatsu, Kenshi

    2016-01-01

    The embryonic brain is one of the tissues most vulnerable to ionizing radiation. In this study, we showed that ionizing radiation induces apoptosis in the neural progenitors of the mouse cerebral cortex, and that the surviving progenitor cells subsequently develop a considerable amount of supernumerary centrosomes. When mouse embryos at Day 13.5 were exposed to γ-rays, brains sizes were reduced markedly in a dose-dependent manner, and these size reductions persisted until birth. Immunostaining with caspase-3 antibodies showed that apoptosis occurred in 35% and 40% of neural progenitor cells at 4 h after exposure to 1 and 2 Gy, respectively, and this was accompanied by a disruption of the apical layer in which mitotic spindles were positioned in unirradiated mice. At 24 h after 1 Gy irradiation, the apoptotic cells were completely eliminated and proliferation was restored to a level similar to that of unirradiated cells, but numerous spindles were localized outside the apical layer. Similarly, abnormal cytokinesis, which included multipolar division and centrosome clustering, was observed in 19% and 24% of the surviving neural progenitor cells at 48 h after irradiation with 1 and 2 Gy, respectively. Because these cytokinesis aberrations derived from excess centrosomes result in growth delay and mitotic catastrophe-mediated cell elimination, our findings suggest that, in addition to apoptosis at an early stage of radiation exposure, radiation-induced centrosome overduplication could contribute to the depletion of neural progenitors and thereby lead to microcephaly. PMID:27367050

  9. A massive hypergiant star as the progenitor of the supernova SN 2005gl.

    PubMed

    Gal-Yam, A; Leonard, D C

    2009-04-16

    Our understanding of the evolution of massive stars before their final explosions as supernovae is incomplete, from both an observational and a theoretical standpoint. A key missing piece in the supernova puzzle is the difficulty of identifying and studying progenitor stars. In only a single case-that of supernova SN 1987A in the Large Magellanic Cloud-has a star been detected at the supernova location before the explosion, and been subsequently shown to have vanished after the supernova event. The progenitor of SN 1987A was a blue supergiant, which required a rethink of stellar evolution models. The progenitor of supernova SN 2005gl was proposed to be an extremely luminous object, but the association was not robustly established (it was not even clear that the putative progenitor was a single luminous star). Here we report that the previously proposed object was indeed the progenitor star of SN 2005gl. This very massive star was likely a luminous blue variable that standard stellar evolution predicts should not have exploded in that state. PMID:19305392

  10. Effect of matrix composition on differentiation of nestin-positive neural progenitors from circulation into neurons

    NASA Astrophysics Data System (ADS)

    Jose, Anumol; Krishnan, Lissy K.

    2010-06-01

    The human peripheral blood mononuclear cell has a mixture of progenitor cells with potential to differentiate into a wide range of lineages. The ability of hematopoietic tissue-derived adult stem cells to differentiate into neural progenitor cells offers an alternative to embryonic stem cells as a viable source for cell transplantation therapies to cure neurodegenerative diseases. This approach could lead to the use of autologous progenitors from blood circulation; however, due to the limited numbers available, in vitro cell expansion may be indispensable. In addition, for successful transplantation there is the requirement of a delivery matrix on which cells can survive and differentiate. In this context we carried out this study to identify a suitable biodegradable matrix on which progenitor cells can home, multiply and differentiate. We designed different compositions of the biomimetic matrix containing fibrin, fibronectin, gelatin, growth factors, laminin and hyaluronic acid. The attached cells expressed proliferation markers in initial periods of culture and between days 6 and 9 in culture they differentiated into neurons and/or astrocytes. The differentiation of progenitors into neurons and asterocyte on the composed matrix was established by morphological and immunochemical analysis. Flow cytometric analysis of cells in culture was employed to track development of neurons which expressed an early marker β-tubulin3 and a terminal marker microtubule-associated protein-2 at a later culture period. In vitro experiments indicate that a highly specific niche consisting of various components of the extracellular matrix, including hyaluronic acid, promote cell homing, survival and differentiation.

  11. Identification of proliferative progenitors associated with prominent postnatal growth of the pons.

    PubMed

    Lindquist, Robert A; Guinto, Cristina D; Rodas-Rodriguez, Jose L; Fuentealba, Luis C; Tate, Matthew C; Rowitch, David H; Alvarez-Buylla, Arturo

    2016-01-01

    The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0-4 (P0-P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2(+)Olig2(+), but by P8 a Sox2(-) subpopulation emerges, suggesting a lineage progression from Sox2(+) 'early' to Sox2(-) 'late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2-P3 Sox2(+) progenitors. These results demonstrate the importance of postnatal Sox2(+)Olig2(+) progenitors in pontine growth and oligodendrogenesis. PMID:27188978

  12. EMT Involved in Migration of Stem/Progenitor Cells for Pituitary Development and Regeneration

    PubMed Central

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    Epithelial–mesenchymal transition (EMT) and cell migration are important processes in embryonic development of many tissues as well as oncogenesis. The pituitary gland is a master endocrine tissue and recent studies indicate that Sox2-expressing stem/progenitor cells actively migrate and develop this tissue during embryogenesis. Notably, although migration activity of stem/progenitor cells in the postnatal period seems to be reduced compared to that in the embryonic period, it is hypothesized that stem/progenitor cells in the adult pituitary re-migrate from their microenvironment niche to contribute to the regeneration system. Therefore, elucidation of EMT in the pituitary stem/progenitor cells will promote understanding of pituitary development and regeneration, as well as diseases such as pituitary adenoma. In this review, so as to gain more insights into the mechanisms of pituitary development and regeneration, we summarize the EMT in the pituitary by focusing on the migration of pituitary stem/progenitor cells during both embryonic and postnatal organogenesis. PMID:27058562

  13. Ex Vivo and In Vivo Lentivirus-Mediated Transduction of Airway Epithelial Progenitor Cells.

    PubMed

    Leoni, Giulia; Wasowicz, Marguerite Y; Chan, Mario; Meng, Cuixiang; Farley, Raymond; Brody, Steven L; Inoue, Makoto; Hasegawa, Mamoru; Alton, Eric W F W; Griesenbach, Uta

    2015-01-01

    A key challenge in pulmonary gene therapy for cystic fibrosis is to provide long-term correction of the genetic defect. This may be achievable by targeting airway epithelial stem/progenitor cells with an integrating vector. Here, we evaluated the ability of a lentiviral vector, derived from the simian immunodeficiency virus and pseudotyped with F and HN envelope proteins from Sendai virus, to transduce progenitor basal cells of the mouse nasal airways. We first transduced basal cell-enriched cultures ex vivo and confirmed efficient transduction of cytokeratin-5 positive cells. We next asked whether progenitor cells could be transduced in vivo. We evaluated the transduction efficiency in mice pretreated by intranasal administration of polidocanol to expose the progenitor cell layer. Compared to control mice, polidocanol treated mice demonstrated a significant increase in the number of transduced basal cells at 3 and 14 days post vector administration. At 14 days, the epithelium of treated mice contained clusters (4 to 8 adjacent cells) of well differentiated ciliated, as well as basal cells suggesting a clonal expansion. These results indicate that our lentiviral vector can transduce progenitor basal cells in vivo, although transduction required denudation of the surface epithelium prior to vector administration. PMID:26471068

  14. Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors.

    PubMed

    Hedlund, Eva; Belnoue, Laure; Theofilopoulos, Spyridon; Salto, Carmen; Bye, Chris; Parish, Clare; Deng, Qiaolin; Kadkhodaei, Banafsheh; Ericson, Johan; Arenas, Ernest; Perlmann, Thomas; Simon, András

    2016-01-01

    Degeneration of dopamine neurons in the midbrain causes symptoms of the movement disorder, Parkinson disease. Dopamine neurons are generated from proliferating progenitor cells localized in the embryonic ventral midbrain. However, it remains unclear for how long cells with dopamine progenitor character are retained and if there is any potential for reactivation of such cells after cessation of normal dopamine neurogenesis. We show here that cells expressing Lmx1a and other progenitor markers remain in the midbrain aqueductal zone beyond the major dopamine neurogenic period. These cells express dopamine receptors, are located in regions heavily innervated by midbrain dopamine fibres and their proliferation can be stimulated by antagonizing dopamine receptors, ultimately leading to increased neurogenesis in vivo. Furthermore, treatment with dopamine receptor antagonists enhances neurogenesis in vitro, both from embryonic midbrain progenitors as well as from embryonic stem cells. Altogether our results indicate a potential for reactivation of resident midbrain cells with dopamine progenitor potential beyond the normal period of dopamine neurogenesis. PMID:27246266

  15. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors.

    PubMed

    Islas, Jose Francisco; Liu, Yu; Weng, Kuo-Chan; Robertson, Matthew J; Zhang, Shuxing; Prejusa, Allan; Harger, John; Tikhomirova, Dariya; Chopra, Mani; Iyer, Dinakar; Mercola, Mark; Oshima, Robert G; Willerson, James T; Potaman, Vladimir N; Schwartz, Robert J

    2012-08-01

    Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR(+). However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca(2+) transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis. PMID:22826236

  16. Cortical and Clonal Contribution of Tbr2 Expressing Progenitors in the Developing Mouse Brain.

    PubMed

    Vasistha, Navneet A; García-Moreno, Fernando; Arora, Siddharth; Cheung, Amanda F P; Arnold, Sebastian J; Robertson, Elizabeth J; Molnár, Zoltán

    2015-10-01

    The individual contribution of different progenitor subtypes towards the mature rodent cerebral cortex is not fully understood. Intermediate progenitor cells (IPCs) are key to understanding the regulation of neuronal number during cortical development and evolution, yet their exact contribution is much debated. Intermediate progenitors in the cortical subventricular zone are defined by expression of T-box brain-2 (Tbr2). In this study we demonstrate by using the Tbr2(Cre) mouse line and state-of-the-art cell lineage labeling techniques, that IPC derived cells contribute substantial proportions 67.5% of glutamatergic but not GABAergic or astrocytic cells to all cortical layers including the earliest generated subplate zone. We also describe the laminar dispersion of clonally derived cells from IPCs using a recently described clonal analysis tool (CLoNe) and show that pair-generated cells in different layers cluster closer (142.1 ± 76.8 μm) than unrelated cells (294.9 ± 105.4 μm). The clonal dispersion from individual Tbr2 positive intermediate progenitors contributes to increasing the cortical surface. Our study also describes extracortical contributions from Tbr2+ progenitors to the lateral olfactory tract and ventromedial hypothalamic nucleus. PMID:24927931

  17. Cortical and Clonal Contribution of Tbr2 Expressing Progenitors in the Developing Mouse Brain

    PubMed Central

    Vasistha, Navneet A.; García-Moreno, Fernando; Arora, Siddharth; Cheung, Amanda F.P.; Arnold, Sebastian J.; Robertson, Elizabeth J.; Molnár, Zoltán

    2015-01-01

    The individual contribution of different progenitor subtypes towards the mature rodent cerebral cortex is not fully understood. Intermediate progenitor cells (IPCs) are key to understanding the regulation of neuronal number during cortical development and evolution, yet their exact contribution is much debated. Intermediate progenitors in the cortical subventricular zone are defined by expression of T-box brain-2 (Tbr2). In this study we demonstrate by using the Tbr2Cre mouse line and state-of-the-art cell line