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Sample records for progenitores siluriformes pimelodidae

  1. Harriscolex nathaliae N. Sp. (Cestoda: Proteocephalidea) from Pseudoplatystoma corruscans (Siluriformes: Pimelodidae) in the Paraná River Basin, Argentina.

    PubMed

    Al Gil de Pertierra, Alicia; de Chambrier, Alain

    2013-06-01

    The proteocephalidean cestode Harriscolex nathaliae n. sp. (Proteocephalidae: Zygobothriinae) is described from the intestine of the spotted sorubim Pseudoplatystoma corruscans (Spix and Agassiz) (Siluriformes: Pimelodidae) from the Paraná River basin in Argentina. This new species differs from the only species of the genus, Harriscolex kaparari (Woodland, 1935), which is a parasite of Pseudoplatystoma tigrinum (Linnaeus) from the Amazon River in Brazil, by its larger scolex (width of 450-750 μm vs. 305-340 μm), the position of the vagina in relation to the cirrus sac (anterior and posterior vs. only anterior), an asymmetrical vaginal sphincter, the arrangement of vitelline follicles (1 narrow longitudinal band on each side of the proglottid vs. 2 pairs of wide longitudinal bands on dorsal and ventral sides), and a higher number of uterine diverticula (22-45 vs. 16-20). Harriscolex nathaliae is covered with 2 types of microtriches, acicular filitriches and gladiate spinitriches.

  2. Complete mitochondrial genome of the Neotropical catfish Pseudoplatystoma magdaleniatum (Siluriformes, Pimelodidae).

    PubMed

    Rangel-Medrano, Jose D; Alzate, Juan F; Márquez, Edna J

    2016-11-01

    The Neotropical freshwater fish Pseudoplatystoma magdaleniatum is a trans-Andean species that belongs to the family of long-whiskered catfishes (family Pimelodidae). In this study, the complete mitochondrial genome of P. magdaleniatum was sequenced using the MiSeq Illumina platform. The complete circular mitogenome is 16,568 bp in length, exhibiting an average GC content of 44.19% and codes for 13 proteins, 2 ribosomal RNA genes and 22 transfer RNA genes. Additionally, it exhibits perfect synteny and similar length with the mitogenome of Pimelodus pictus.

  3. Molecular differentiation of species of the genus Zungaro (Siluriformes, Pimelodidae) from the Amazon and Paraná-Paraguay River basins in Brazil.

    PubMed

    Boni, T A; Padial, A A; Prioli, S M A P; Lucio, L C; Maniglia, T C; Bignotto, T S; Panarari-Antunes, R S; Prioli, R A; Prioli, A J

    2011-11-10

    Fish species of the Zungaro genus (Siluriformes, Pimelodidae) are amongst the largest migratory fish in Latin America and have considerable economic importance for commercial fishing in Brazil. However, natural populations of this large catfish are experiencing a severe decline. There are significant taxonomical inconsistencies for this fish. Two geographically separated species of the fish were initially described, one endemic in the Amazon and another in the Paraná-Paraguay River basins. A taxonomic review had recently proposed that there is only one Zungaro species in Brazil, based on morphological data. We made a molecular study of Zungaro populations in an attempt to solve taxonomical inconsistencies and to analyze genetic diversity in natural populations of this genus. We analyzed two regions of the mitochondrial DNA (the control region and the ATPase 6 gene region) of individuals sampled from the Paraná-Paraguay River and Amazon River basins. Analyses based on p-distances and maximum likelihood phylogenetic models showed a genetic difference between populations corresponding to different species. Genetic differentiation between Zungaro populations was at the same level as that observed between other Siluriformes species, using the same DNA sequences. We conclude that Zungaro species of the Paraná-Paraguay River basin do not belong to the same species found in the Amazon basin. This finding has a significant implication for conservation of this fish, given that populations are disappearing at a high rate in the Paraná-Paraguay River basin, mainly due to impoundments.

  4. Cytogenetic studies in the redtail catfish, Phractocephalus hemioliopterus (Bloch & Schneider, 1801) (Siluriformes, Pimelodidae) a giant fish from Amazon basin.

    PubMed

    Swarça, Ana Claudia; Dias, Ana Lucia; Fenocchio, Alberto Sergio

    2017-01-01

    The objective of this study was to cytogenetically analyze Phractocephalus hemioliopterus comparing the findings with other data to infer relationships among Pimelodidae species. The results revealed a diploid number of 2n = 56 and the karyotype composed of 16 metacentric, 20 submetacentric, 6 subtelocentric and 14 acrocentric chromosomes (FN = 98). The Ag-NORs, 18S rDNA and CMA3 signals were coincident in location occupying the short arm of an acrocentric chromosome pair (23(th)), in a secondary constriction. The 5S rDNA genes were localized near the centromere on the short arms of one submetacentric chromosome pair. C-bands were localized predominantly in the terminal regions of chromosomes, including the AgNORs and a small metacentric pair with a conspicuous positive band on interstitial region. This chromosome pair could be considered a species-specific cytogenetic marker.

  5. 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.

  6. 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.

  7. A phylogenetic analysis of the major groups of catfishes (Teleostei: Siluriformes) using rag1 and rag2 nuclear gene sequences.

    PubMed

    Sullivan, John P; Lundberg, John G; Hardman, Michael

    2006-12-01

    Higher-level relationships among catfishes were investigated by parsimony, maximum likelihood and Bayesian analyses of two nuclear genes across 110 catfish species representing 36 of 37 families and Conorhynchos (family incertae sedis). Analysis of 3660 aligned base pairs from the rag1 and rag2 genes confirms monophyly of Siluriformes, of most siluriform families and of a number of multifamily groups, some recognized, some novel. South American Loricarioidei are recovered as the sistergroup to other catfishes which are divided into Diplomystidae and Siluroidei. This result contrasts with the prevailing hypothesis that Diplomystidae is the sister to all other catfishes. Monophyly of Siluroidei is supported by rag data including a unique three-codon deletion from rag1. Deep within Siluroidei are 12 large, strongly supported groups with poorly resolved interrelationships. Five are single families: Cetopsidae, Plotosidae, Chacidae, Siluridae and Pangasiidae. Four others are monophyletic taxa ranked here as superfamilies: Clarioidea (Clariidae, Heteropneustidae), Arioidea (Ariidae, Anchariidae), Pimelodoidea (Pimelodidae, Pseudopimelodidae, Heptapteridae, Conorhynchos), Ictaluroidea (Ictaluridae, Cranoglanididae). South American Doradoidea (Doradidae, Auchenipteridae) and Aspredinidae are a sistergroup pair. Sisoroidea (without Aspredinidae), Ailia+Laides, Horabagridae, and Bagridae (without Rita) form a large, predominantly Asian clade, "Big Asia." Mochokidae, Malapteruridae, Amphiliidae, Claroteidae, and African schilbids are united as a species-rich African clade, "Big Africa." The three large continental clades, "Big Asia," "Big Africa" and Neotropical Loricarioidei suggest a prevalence of intracontinental diversification of catfishes. South America is the home of the Gymnotiformes, putative sistergroup of catfishes, plus two of the deepest siluriform clades, Loricarioidei and Diplomystidae, thus suggesting an ancient siluriform presence if not origin there. The rag

  8. Complete mitochondrial genome from South American catfish Pseudoplatystoma reticulatum (Eigenmann & Eigenmann) and its impact in Siluriformes phylogenetic tree.

    PubMed

    Villela, Luciana Cristine Vasques; Alves, Anderson Luis; Varela, Eduardo Sousa; Yamagishi, Michel Eduardo Beleza; Giachetto, Poliana Fernanda; da Silva, Naiara Milagres Augusto; Ponzetto, Josi Margarete; Paiva, Samuel Rezende; Caetano, Alexandre Rodrigues

    2017-02-01

    The cachara (Pseudoplatystoma reticulatum) is a Neotropical freshwater catfish from family Pimelodidae (Siluriformes) native to Brazil. The species is of relative economic importance for local aquaculture production and basic biological information is under development to help boost efforts to domesticate and raise the species in commercial systems. The complete cachara mitochondrial genome was obtained by assembling Illumina RNA-seq data from pooled samples. The full mitogenome was found to be 16,576 bp in length, showing the same basic structure, order, and genetic organization observed in other Pimelodidae, with 13 protein-coding genes, 2 rNA genes, 22 trNAs, and a control region. Observed base composition was 24.63% T, 28.47% C, 31.45% A, and 15.44% G. With the exception of NAD6 and eight tRNAs, all of the observed mitochondrial genes were found to be coded on the H strand. A total of 107 SNPs were identified in P. reticulatum mtDNA, 67 of which were located in coding regions. Of these SNPs, 10 result in amino acid changes. Analysis of the obtained sequence with 94 publicly available full Siluriformes mitogenomes resulted in a phylogenetic tree that generally agreed with available phylogenetic proposals for the order. The first report of the complete Pseudoplatystoma reticulatum mitochondrial genome sequence revealed general gene organization, structure, content, and order similar to most vertebrates. Specific sequence and content features were observed and may have functional attributes which are now available for further investigation.

  9. Morphology of the gas bladder in bumblebee catfishes (Siluriformes, Pseudopimelodidae).

    PubMed

    Birindelli, José L O; Shibatta, Oscar A

    2011-07-01

    The gross morphology of the gas bladder is described and compared for representatives of all valid genera of Pseudopimelodidae (Siluriformes). Cephalosilurus albomarginatus and species of Batrochoglanis, and Microglanis have the most basic form: a large, cordiform gas bladder with a simple internal T-shaped septum. Cephalosilurus apurensis, C. fowleri, and C. nigricauda also have a large, cordiform gas bladder, but they have well-developed trabeculae associated with the internal T-shaped septum, and a pair of well-developed constrictor muscles inserted on the external wall; the latter feature is present in most species of Pimelodidae, but absent in all other catfishes. The monotypic Lophiosilurus alexandri also has well-developed constrictor muscles, and its gas bladder is moderately sized. The species of Pseudopimelodus and Cruciglanis have a diminutive gas bladder partially divided into two lateral sacs without internal communication, and lack constrictor muscles. The parapophysis of the fourth vertebra is a wide and long shelf connected to the dorsal surface of the gas bladder in most pseudopimelodid genera. However, in the species of Pseudopimelodus and Cruciglanis the parapophysis of the fourth vertebra is shorter and has its anterior ramus folded back, partially covering the gas bladder anteroventrally; and the tympanic opening is smaller than in species of the other genera. Five phylogenetic characters are proposed based on the morphology of the gas bladder and associated structures in species of Pseudopimelodidae, and the evolution of those characters in the family is discussed. J. Morphol., 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc.

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

    PubMed

    Ohara, Willian Massaharu; Neuhaus, Emanuel Bruno

    2016-07-11

    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).

  11. Tapeworms (Cestoda: Proteocephalidea) of firewood catfish Sorubimichthys planiceps (Siluriformes: Pimelodidae) from the Amazon River.

    PubMed

    de Chambrier, Alain; Scholz, Tomás

    2008-03-01

    A survey of proteocephalidean cestodes found in the firewood catfish Sorubimichthys planiceps (Spix et Agassiz) from the Amazon River is provided. The following taxa parasitic in S. planiceps are redescribed on the basis of their type specimens and material collected recently in the Amazon River, near the type localities in Brazil, and in Iquitos, Peru: Monticellia lenha Woodland, 1933; Nomimoscolex lenha (Woodland, 1933) (syn. Proteocephalus lenha Woodland, 1933); and Monticellia megacephala Woodland, 1934, for which a new genus, Lenhataenia, is proposed, with L. megacephala (Woodland, 1934) comb. n. as its type and only species. The new genus is a member of the Monticelliinae, i.e. has all genital organs in the cortex, and is most similar to Chambriella in possessing biloculate suckers and lacking a metascolex. It differs in the morphology of the cirrus-sac that contains a strongly coiled, thick-walled internal sperm duct (vas deferens) and a muscular cirrus of the appearance typical of most proteocephalideans, whereas that of Chambriella is sigmoid, with voluminous, tightly sinuous thick-walled internal sperm duct. In addition, Lenhataenia possesses a well developed internal musculature, whereas the internal musculature of Chambriella is weakly developed, formed by a low number of muscle fibres. The scolex morphology and distribution of microtriches of Peltidocotyle lenha (Woodland, 1933) (syn. Othinoscolex lenha Woodland, 1933 and Othinoscolex myzofer Woodland, 1933), Chambriella sp. and Choanoscolex sp. are described using scanning electron microscopy. The two latter taxa may be new for science and are reported from S. planiceps for the first time.

  12. 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

  13. 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

    2014-05-09

    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.

  14. Mitochondrial genome of the Trans-Andean shovelnose catfish Sorubim cuspicaudus (Siluriformes, Pimelodidae).

    PubMed

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

    2016-11-01

    The Trans-Andean shovelnose catfish Sorubim cuspicaudus is the largest species within the genus Sorubim. In this work, the pyrosequencing technology was used to obtain the complete mitochondrial genome sequence of S. cuspicaudus. The 16,544 bp molecule contains 13 protein-coding genes, 22 tRNAs, 2 ribosomal RNAs and exhibit perfect synteny with other South-American catfishes.

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

    PubMed

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

    2012-12-01

    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.

  16. 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.

  17. 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

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

    PubMed

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

    2015-05-01

    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 F ST. 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.

  19. 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.

  20. New species of Ameloblastella Kritsky, Mendoza-Franco & Scholz, 2000 and Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986 (Monogenea: Dactylogyridae) infecting the gills of catfishes (Siluriformes) from the Peruvian Amazonia.

    PubMed

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

    2016-11-01

    During a research on gill ectoparasites of siluriform fishes from the Peruvian Amazonia, the following monogeneans were found: Ameloblastella edentensis n. sp. from Hypophthalmus edentatus Spix & Agassiz; Ameloblastella peruensis n. sp. from Hypophthalmus sp.; Ameloblastella formatrium n. sp. from Pimelodidae gen. sp. (type-host) and Duopalatinus cf. peruanus Eigenmann & Allen; Ameloblastella unapioides n. sp. from Sorubim lima (Bloch & Schneider) (type-host) and Pimelodus sp; Cosmetocleithrum tortum n. sp. from Nemadoras hemipeltis (Eigenmann); and Cosmetocleithrum bifurcum n. sp. from Hassar orestis (Steindachner) (both Doradidae). All new species described herein are mainly differentiated from their congeners based on the morphology of the copulatory complex. The pimelodids H. edentatus and S. lima, and the doradids N. hemipeltis and H. orestis represent new hosts species for species of Ameloblastella Kritsky, Mendoza-Franco & Scholz, 2000 and Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986, respectively. The morphological diagnosis of the present species of Ameloblastella and Cosmetocleithrum also supported by a previous molecular analysis of these species is briefly discusssed herein.

  1. 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. © 2015 The Fisheries Society of the British Isles.

  2. Analysis of heterochromatin by combination of C-banding and CMA3 and DAPI staining in two fish species (Pimelodidae, Siluriformes).

    PubMed

    Swarça, Ana C; Fenocchio, Alberto S; Cestari, Marta M; Dias, Ana L

    2003-09-01

    The chromosomes of Steindachneridion sp. (2n = 56) and Rhamdia quelen (2n = 58) were analyzed by C-banding (CB) and Chromomycin A3 (CMA3) and 4,6-diamidino-2-phenylindole (DAPI) staining, separately and consecutively, in order to understand the role of base-specific fluorochrome treatment after CB. Both species' chromosomes shared common staining profiles as follows. CB with Giemsa (CBG) revealed weak heterochromatic blocks in the telomeric regions of some chromosomes and conspicuous bands on the short arms of one chromosome pair, where nucleolar organizer regions (NORs) were evidenced by silver-staining. Without CB pretreatment, the NORs were stained conspicuously with CMA3, but not with DAPI. The latter uniformly stained all chromosomes, but leaving the NORs pale. Combination of CMA3 or DAPI staining with CB showed distinctive fluorescent blocks in the NOR-bearing short arms of the single chromosome pair along with several bright fluorescent signals on other chromosomes, which were not evidenced by single CMA3 or DAPI staining. These results suggest a modification of chromatin structure by CB treatment, which may increase the stainability of CMA3 and DAPI.

  3. Molecular phylogeny and a chronology of diversification for "phractocephaline" catfishes (Siluriformes: Pimelodidae) based on mitochondrial DNA and nuclear recombination activating gene 2 sequences.

    PubMed

    Hardman, Michael; Lundberg, John G

    2006-08-01

    The Maracaibo basin in northwestern Venezuela is home to over 108 species of freshwater fishes, over half of which occur nowhere else. The rise of the Mérida Andes between 8 and 10 million years ago is believed to have divided a preexisting biota and facilitated allopatric speciation. The distinctive "phractocephaline" clade of pimelodid catfishes has a distribution that includes the Maracaibo historically and today is represented by Perrunichthys (Maracaibo endemic), Leiarius, Phractocephalus, and Steindachneridion. A resolved and well-supported phylogeny was obtained from the phylogenetic analysis of over 3.4kb (including cytochrome b, NADH dehydrogenase subunit 1, recombination activating gene subunit 2). Rates of divergence among "phractocephalines" were calibrated with fossil material and the Mérida uplift. These independent calibrators provided different node-age estimates when the rates were applied separately to the gene partitions (mtDNA and rag2). Node-age discrepancies were particularly evident at older nodes. This is due to two factors: (1) multiple substitution of mtDNA underestimates the amount of change and therefore time since cladogenesis, whereas (2) calibration of an ancient node with fossils produces an artificially slow rate (due to the masking of divergence through multiple substitution) that overestimates time when applied to younger nodes. Node-age estimates provided by the more slowly evolving rag2 sequences were more consistent with other sources of historical inference, e.g., paleogeography and the fossil record. Given these points, we provide a synthetic chronology of diversification and discuss the reasons for its preference. The phylogeny and synthetic chronology suggest Perrunichthys perruno (Maracaibo endemic) and Leiarius pictus (Orinoco and Guianas) to be a vicariant species pair that last shared a common ancestor during the period of Mérida uplift.

  4. 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. © 2015 Wiley Periodicals, Inc.

  5. 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.

  6. Molecular phylogeny of Neotropical monogeneans (Platyhelminthes: Monogenea) from catfishes (Siluriformes).

    PubMed

    Mendoza-Palmero, Carlos A; Blasco-Costa, Isabel; Scholz, Tomáš

    2015-03-18

    The phylogenetic relationships of dactylogyrids (Monogenea: Dactylogyridae) parasitising catfishes (Siluriformes) from the Neotropical region were investigated for the first time. Partial sequences of the 28S rRNA gene of 40 specimens representing 25 dactylogyrid species were analysed together with sequences from GenBank using Bayesian inference, Maximum likelihood and Parsimony methods. Monophyly of dactylogyrids infecting catfishes and the Ancyrocephalinae was evaluated using the Approximately Unbiased test. The Ancyrocephalinae is a paraphyletic group of species clustering in three main clades as follows: (i) clade A comprising freshwater dactylogyrids from the Holarctic parasitising perciforms clustering together with species (Ameloblastella, Unibarra and Vancleaveus) parasitising Neotropical catfishes; (ii) clade B including species of Dactylogyrus (Dactylogyrinae) and Pseudodactylogyrus (Pseudodactylogyrinae) along with Ancyrocephalus mogurndae, and marine dactylogyrids with cosmopolitan distribution, parasites of scorpaeniforms and perciforms, along with the freshwater Cichlidogyrus and Scutogyrus (infecting African cichlids [Cichlidae]) and (iii) clade C containing exclusively dactylogyrids of siluriforms, freshwater and marine, with Palaearctic, Ethiopian, Oriental and Neotropical distributions; species of Aphanoblastella and Dactylogyridae gen. sp. 4 from the Neotropical region clustering together with species allocated in the Ancylodiscoidinae, along with species of Cosmetocleithrum, Demidospermus and Dactylogyridae gen. spp. The position of the Ancylodiscoidinae within a larger clade of dactylogyrids (ancyrocephalines) indicates that this subfamily does not represent a natural group. Instead, species allocated to this clade (dactylogyrids of siluriforms along with species of the Ancylodiscoidinae) should be considered as a separate subfamily within the Dactylogyridae. The erection of this taxon requires the search for morphological diagnostic characters

  7. A Time-Calibrated Mitogenome Phylogeny of Catfish (Teleostei: Siluriformes)

    PubMed Central

    Kappas, Ilias; Vittas, Spiros; Pantzartzi, Chrysoula N.; Drosopoulou, Elena; Scouras, Zacharias G.

    2016-01-01

    A very significant part of the world’s freshwater ichthyofauna is represented by ancient, exceptionally diverse and cosmopolitan ray-finned teleosts of the order Siluriformes. Over the years, catfish have been established as an exemplary model for probing historical biogeography at various scales. Yet, several tantalizing gaps still exist in their phylogenetic history, timeline and mode of diversification. Here, we re-examine the phylogeny of catfish by assembling and analyzing almost all publicly available mitogenome data. We constructed an ingroup matrix of 62 full-length mitogenome sequences from 20 catfish families together with four cypriniform outgroups, spanning 15,557 positions in total. Partitioned maximum likelihood analyses and Bayesian relaxed clock dating using fossil age constraints provide some useful and novel insights into the evolutionary history of this group. Loricarioidei are recovered as the first siluriform group to diversify, rendering Neotropics the cradle of the order. The next deepest clade is the South American Diplomystoidei placed as a sister group to all the remaining Siluroidei. The two multifamilial clades of “Big Asia” and “Big Africa” are also recovered, albeit nodal support for the latter is poor. Within “Big Asia”, Bagridae are clearly polyphyletic. Other interfamilial relationships, including Clariidae + Heteropneustidae, Doradidae + Auchenipteridae and Ictaluridae + Cranoglanididae are robustly resolved. Our chronogram shows that siluriforms have a Pangaean origin, at least as far back as the Early Cretaceous. The inferred timeline of the basal splits corroborates the “Out-of-South America” hypothesis and accords well with the fossil record. The divergence of Siluroidei most likely postdated the final separation of Africa and South America. An appealing case of phylogenetic affinity elaborated by biogeographic dispersal is exemplified by the Early Paleogene split between the Southeast Asian Cranoglanididae

  8. Reducing the information gap on Loricarioidei (Siluriformes) mitochondrial genomics.

    PubMed

    Moreira, Daniel Andrade; Buckup, Paulo Andreas; Furtado, Carolina; Val, Adalberto Luis; Schama, Renata; Parente, Thiago Estevam

    2017-05-04

    The genetic diversity of Neotropical fish fauna is underrepresented in public databases. This distortion is evident for the order Siluriformes, in which the suborders Siluroidei and Loricarioidei share equivalent proportion of species, although far less is known about the genetics of the latter clade, endemic to the Neotropical Region. Recently, this information gap was evident in a study about the structural diversity of fish mitochondrial genomes, and hampered a precise chronological resolution of Siluriformes. It has also prevented molecular ecology investigations about these catfishes, their interactions with the environment, responses to anthropogenic changes and potential uses. Using high-throughput sequencing, we provide the nearly complete mitochondrial genomes for 26 Loricariidae and one Callichthyidae species. Structural features were highly conserved. A notable exception was identified in the monophyletic clade comprising species of the Hemiancistrus, Hypostomini and Peckoltia-clades, a ~60 nucleotide-long deletion encompassing the seven nucleotides at the 3' end of the Conserved Sequence Block (CSB) D of the control region. The expression of mitochondrial genes followed the usual punctuation pattern. Heteroplasmic sites were identified in most species. The retrieved phylogeny strongly corroborates the currently accepted tree, although bringing to debate the relationship between Schizolecis guntheri and Pareiorhaphis garbei, and highlighting the low genetic variability within the Peckoltia-clade, an eco-morphologically diverse and taxonomically problematic group. Herein we have launched the use of high-throughput mitochondrial genomics in the studies of the Loricarioidei species. The new genomic resources reduce the information gap on the molecular diversity of Neotropical fish fauna, impacting the capacity to investigate a variety of aspects of the molecular ecology and evolution of these fishes. Additionally, the species showing the partial CSB-D are

  9. Dactylogyridean monogeneans of the siluriform fishes of the Old World.

    PubMed

    Lim, L H; Timofeeva, T A; Gibson, D I

    2001-11-01

    This is a catalogue and discussion of the known dactylogyridean monogenean genera of siluriform fishes of the Old World. Of a total of 38 nominal genera, only 19 are considered valid. Seventeen of these 19 genera are currently in the Ancyrocephalidae (containing the Ancyrocephalinae and Ancylodiscoidinae), whilst the other two (Neocalceostoma and Neocalceostomoides) are in the Neocalceostomatidae. The 17 genera are Anchylodiscus, Ancylodiscoides, Bagrobdella, Bifurcohaptor, Bychowskyella, Chauhanellus, Cornudiscoides, Hamatopeduncularia, Mizelleus, Paraquadriacanthus, Pseudancylodiscoides, Protoancylodiscoides, Quadriacanthus, Schilbetrema, Schilbetrematoides, Synodontella and Thaparocleidus. Clariotrema Long, 1981 and Neobychowskyella Ma, Wang & Li, 1983 are considered synonyms of Bychowskyella Akhmerov, 1952, Anacornuatus Dubey, Gupta & Agarwal, 1992 is considered a synonym of Quadriacanthus Paperna, 1961, Mizellebychowskia Gupta & Sachdeva, 1990 is considered a synonym of Neocalceostoma Tripathi, 1959 and Hargitrema Tripathi, 1959 is treated as a synonym of Hamatopeduncularia Yamaguti, 1953. It is proposed that the Ancylodiscoidinae be raised to family status within the order Dactylogyridea to accommodate these 17 'ancyrocephalid' genera from siluriforms, together with Malayanodiscoides and Notopterodiscoides from notopterids. A key and the diagnostic characteristics of the 19 recognised dactylogyridean genera from catfishes plus two from notopterids, together with a list of species and synonyms, are included. New combinations made in this work are Thaparocleidus avicularia (Chen, 1987) n. comb., T. calyciflorus (Chen, 1987) n. comb., T. choanovagina (Luo & Lang, 1981) n. comb., T. dissimilis (Chen, 1988) n. comb., T. leiocassis (Reichenbach-Klinke, 1959) n. comb., T. meticulosa (Chen, 1987) n. comb., T. parasoti (Zhao & Ma, 1999) n. comb., T. persculpus (Chen, 1987) n. comb., T. valga (Chen, 1987) n. comb. and T. wulingensis (Yao & Wang, 1997) n. comb. [all

  10. 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.

  11. Resident vascular progenitor cells.

    PubMed

    Torsney, Evelyn; Xu, Qingbo

    2011-02-01

    Homeostasis of the vessel wall is essential for maintaining its function, including blood pressure and patency of the lumen. In physiological conditions, the turnover rate of vascular cells, i.e. endothelial and smooth muscle cells, is low, but markedly increased in diseased situations, e.g. vascular injury after angioplasty. It is believed that mature vascular cells have an ability to proliferate to replace lost cells normally. On the other hand, recent evidence indicates stem/progenitor cells may participate in vascular repair and the formation of neointimal lesions in severely damaged vessels. It was found that all three layers of the vessels, the intima, media and adventitia, contain resident progenitor cells, including endothelial progenitor cells, mesenchymal stromal cells, Sca-1+ and CD34+ cells. Data also demonstrated that these resident progenitor cells could differentiate into a variety of cell types in response to different culture conditions. However, collective data were obtained mostly from in vitro culture assays and phenotypic marker studies. There are many unanswered questions concerning the mechanism of cell differentiation and the functional role of these cells in vascular repair and the pathogenesis of vascular disease. In the present review, we aim to summarize the data showing the presence of the resident progenitor cells, to highlight possible signal pathways orchestrating cell differentiation toward endothelial and smooth muscle cells, and to discuss the data limitations, challenges and controversial issues related to the role of progenitors. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  12. The Crab Nebula's progenitor

    NASA Technical Reports Server (NTRS)

    Nomoto, K.; Sugimoto, D.; Sparks, W. M.; Fesen, R. A.; Gull, T. R.; Miyaji, S.

    1982-01-01

    The initial mass of the Crab Nebula's progenitor star is estimated by comparing the observed nebular chemical abundances with detailed evolutionary calculations for 2.4- and 2.6-solar-mass helium cores of stars with masses of 8 to 10 solar masses. The results indicate that the mass of the Crab's progenitor was between the upper limit of about 8 solar masses for carbon deflagration and the lower limit of about 9.5 solar masses set by the dredge-up of the helium layer before the development of the helium-burning convective region. A scenario is outlined for the evolution of the progenitor star. It is suggested that the Crab Nebula was probably the product of an electron-capture supernova.

  13. 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

  14. 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. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

  15. Orientatractis moraveci n. sp. and Rondonia rondoni Travassos, 1920 (Nematoda: Atractidae), parasites of Pimelodus blochii (Osteichthyes, Pimelodidae) from the Acre and Xapuri Rivers, Western Amazon, Brazil.

    PubMed

    Cavalcante, Pedro H O; Silva, Maralina T; Santos, Everton G N; Chagas-Moutinho, Vanessa A; Santos, Claudia P

    2017-02-01

    The fish fauna in the State of Acre represents 10·7% of all fish species recorded from Brazil, but, despite this, there are few fish parasite studies in this area. The recent expansion of fish farming in Acre prompted a need for helminthological studies of the most commonly consumed fish species in the area, Pimelodus blochii (Pimelodidae). The aim of this study was to analyse the helminth fauna of P. blochii from the Acre and Xapuri Rivers in Northwestern Brazil. Numerous nematodes were collected from the intestine and two species of the family Atractidae were identified: Rondonia rondoni Travassos, 1920 and Orientatractis moraveci n. sp. The new species is distinguished from its congeners mainly by having: 10 pairs of caudal papillae (3 pairs pre-cloacal, 2 pairs ad-cloacal and 5 pairs post-cloacal); unequal spicules of 161-198 and 69-100 µ m long; and a gubernaculum 38-58 µ m long with an antero-lateral process. Morphological and ultrastructural data on O. moraveci n. sp. and R. rondoni are presented, in addition to new genetic data based on partial 18S rDNA and 28S rDNA. The taxonomic status of Labeonema synodontisi (Vassiliadès, 1973) is discussed, suggesting that it should be returned to the genus Raillietnema.

  16. Lung Epithelial Progenitor Cells

    PubMed Central

    Rawlins, Emma L.

    2008-01-01

    The current enthusiasm for stem cell research stems from the hope that damaged or diseased tissues may one day be repaired through the manipulation of endogenous or exogenous stem cells. The postnatal human respiratory system is highly accessible and provides unique opportunities for the application of such techniques. Several putative adult lung epithelial stem cells have been identified in the mouse model system. However, their in vivo capabilities to contribute to different lineages, and their control mechanisms, remain unclear. If stem cell–based therapies are to be successful in the lung, it is vitally important that we understand the normal behavior of adult lung stem cells, and how this is regulated. Lung embryonic progenitor cells are much better defined and characterized than their adult counterparts. Moreover, experiments on a variety of developing tissues are beginning to uncover general mechanisms by which embryonic progenitors influence final organ size and structure. This provides a framework for the study of lung embryonic progenitor cells, facilitating experimental design and interpretation. A similar approach to investigating adult lung stem cells could produce rapid advances in the field. PMID:18684716

  17. 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

  18. 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

  19. 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

  20. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. Circulating Progenitor Cells and Scleroderma

    PubMed Central

    2010-01-01

    Scleroderma (systemic sclerosis) is a disease of unknown origins that involves tissue ischemia and fibrosis in the skin and internal organs such as the lungs. The tissue ischemia is due to a lack of functional blood vessels and an inability to form new blood vessels. Bone marrow–derived circulating endothelial progenitor cells play a key role in blood vessel repair and neovascularization. Scleroderma patients appear to have defects in the number and function of circulating endothelial progenitor cells. Scleroderma patients also develop fibrotic lesions, possibly as the result of tissue ischemia. Fibroblast-like cells called fibrocytes that differentiate from a different pool of bone marrow–derived circulating progenitor cells seem to be involved in this process. Manipulating the production, function, and differentiation of circulating progenitor cells represents an exciting new possibility for treating scleroderma. PMID:18638425

  3. A new genus and two new species of dactylogyrid monogeneans from gills of Neotropical catfishes (Siluriformes: Doradidae and Loricaridae).

    PubMed

    Acosta, Aline Angelina; Scholz, Tomáš; Blasco-Costa, Isabel; Alves, Philippe Vieira; da Silva, Reinaldo José

    2017-09-19

    A new genus of dactylogyrid monogeneans (Ancyrocephalinae), Paracosmetocleithrum n. gen., is erected to accommodate P. trachydorasi n. sp. from Trachydoras paraguayensis (Siluriformes: Doradidae) in the Upper Paraná River basin, Brazil. The new genus differs from Neotropical dactylogyrids in the presence of a well-developed ornamentation in the middle portion of the ventral bar, and a sclerotized patch on the surface of the dorsal bar with an inconspicuous medial process that possesses two submedial projections arising from the tapered ends of this patch. In addition, Demidospermus rhinelepisi n. sp. is described from Rhinelepis aspera (Siluriformes: Loricariidae). The new species, which is the fifth species of the genus described from loricariids, can be differentiated from congeners by the possession of a sclerotized patch attached to the middle portion of the ventral bar, and by morphology of the accessory piece, which presents broad ends, tapering in the centre, rounded proximal end, distal end folding on both sides with folds extending to approximately ¾ of the accessory piece length. Molecular data on both new species are also provided and species composition of Demidospermus, recently revealed as polyphyletic by molecular studies including the present one, is discussed. Copyright © 2017. Published by Elsevier B.V.

  4. Mesenchymal progenitor cells for the osteogenic lineage.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  5. Multilocus analysis of the catfish family Trichomycteridae (Teleostei: Ostariophysi: Siluriformes) supporting a monophyletic Trichomycterinae.

    PubMed

    Ochoa, Luz E; Roxo, Fabio F; DoNascimiento, Carlos; Sabaj, Mark H; Datovo, Aléssio; Alfaro, Michael; Oliveira, Claudio

    2017-10-01

    Trichomycteridae is the second most diverse family of the order Siluriformes, its members are widely distributed through the freshwaters of Central and South America, exhibiting an exceptional ecological and phenotypic disparity. The most diverse subfamily, Trichomycterinae, represented mainly by the genus Trichomycterus, historically has been recognized as non-monophyletic and various characters used to unite or divide its constituents are repeatedly called into question. No comprehensive molecular phylogenetic hypothesis regarding relationships of trichomycterids has been produced, and the present study is the first extensive phylogeny for the family Trichomycteridae, based on a multilocus dataset of three mitochondrial loci and two nuclear markers (3284bp total). Our analysis has the most comprehensive taxon-sampling of the Trichomycteridae published so far, including members of all subfamilies and a vast representation of Trichomycterus diversity. Analysis of these data showed a phylogenetic hypothesis with broad agreement between the Bayesian (BI) and maximum-likelihood (ML) trees. The results provided overwhelming support for the monophyletic status of Copionodontinae, Stegophilinae, Trichomycterinae, and Vandelliinae, but not Sarcoglanidinae and Glanapteryginae. A major feature of our results is the support to the current conceptualization of Trichomycterinae, which includes Ituglanis and Scleronema and excludes the "Trichomycterus" hasemani group. Divergence time analysis based on DNA substitution rates suggested a Lower Cretaceous origin of the family and the divergence events at subfamilial level shaped by Paleogene events in the geohistory of South America. This hypothesis lays a foundation for an array of future studies of evolution and biogeography of the family. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Comparative anatomy of the cheek muscles within the Centromochlinae subfamily (Ostariophysi, Siluriformes, Auchenipteridae).

    PubMed

    Sarmento-Soares, Luisa Maria; Porto, Marcovan

    2006-02-01

    Glanidium melanopterum Miranda Ribeiro, a typical representative of the subfamily Centromochlinae (Siluriformes: Auchenipteridae), is herein described myologically and compared to other representative species within the group, Glanidium ribeiroi, G. leopardum, Tatia neivai, T. intermedia, T. creutzbergi, Centromochlus heckelii, and C. existimatus. The structure of seven pairs of striated cephalic muscles was compared anatomically: adductor mandibulae, levator arcus palatini, dilatator operculi, adductor arcus palatini, extensor tentaculi, retractor tentaculi, and levator operculi. We observed broad adductor mandibulae muscles in both Glanidium and Tatia, catfishes with depressed heads and smaller eyes. Similarities between muscles were observed: the presence of a large aponeurotic insertion for the levator arcus palatini muscle; an adductor arcus palatini muscle whose origin spread over the orbitosphenoid, pterosphenoid, and parasphenoid; and the extensor tentaculi muscle broadly attached to the autopalatine. There is no retractor tentaculi muscle in either the Glanidium or Tatia species. On the other hand, in Centromochlus, with forms having large eyes and the tallest head, the adductor mandibulae muscles are slim; there is a thin aponeurotic or muscular insertion for the levator arcus palatini muscle; the adductor arcus palatini muscle originates from a single osseous process, forming a keel on the parasphenoid; the extensor tentaculi muscle is loosely attached to the autopalatine, permitting exclusive rotating and sliding movements between this bone and the maxillary. The retractor tentaculi muscle is connected to the maxilla through a single tendon, so that both extensor and retractor tentaculi muscles contribute to a wide array of movements of the maxillary barbels. A discussion on the differences in autopalatine-maxillary movements among the analyzed groups is given. (c) 2005 Wiley-Liss, Inc.

  7. Genomic organization of repetitive DNAs highlights chromosomal evolution in the genus Clarias (Clariidae, Siluriformes).

    PubMed

    Maneechot, Nuntiya; Yano, Cassia Fernanda; Bertollo, Luiz Antonio Carlos; Getlekha, Nuntaporn; Molina, Wagner Franco; Ditcharoen, Sukhonthip; Tengjaroenkul, Bundit; Supiwong, Weerayuth; Tanomtong, Alongklod; de Bello Cioffi, Marcelo

    2016-01-01

    The genus Clarias (Clariidae, Siluriformes) contains at least 61 species naturally spread over vast regions of Asia, India and Africa. However, Clarias species have also been introduced in many different countries and represent the most widespread catfishes in the world. These fishes are also known as "walking catfishes" due to their ability to move over land. A large degree of chromosomal variation has been previously found in this family, mainly using conventional cytogenetic investigations, with diploid chromosome numbers ranging between 48 and 100. In this study, we analyzed the karyotype structure and distribution of four repetitive DNA sequences (5S and 18S rDNAs and (CA)15 and (GA)15 microsatellites) in three Clarias species (C. batrachus, C. gariepinus, C. macrocephalus), as well as in a probable natural hybrid of the two latter species from different Thailand river basins. Clarias gariepinus and C. macrocephalus had 2n = 56 and 2n = 54, respectively, as well as karyotypes composed mainly by metacentric and submetacentric chromosomes. Their karyotypes differed in the number and location of 5S and 18S rDNA sites and in the degree of microsatellite accumulation. An intermediate chromosomal pattern incorporating those of the parental species was found in the probable hybrid, confirming its interspecific origin. Clarias batrachus had 2n = 104 chromosomes and its karyotype was dominated by mainly acrocentric elements, indicating that unusual multiple centric fissions were involved in its karyotype differentiation. The karyotype of this species presented an unexpected dispersion of ribosomal DNAs, possessing 54 and 12 sites of 5S and 18S rDNAs, respectively, as well as a high accumulation and differential distribution of both microsatellite repeats, representing 'hot spots' for chromosomal rearrangement. Both conventional and molecular cytogenetic markers were useful tools for demonstrating remarkable evolutionary dynamism and highlighting multiple

  8. Distribution and habitat suitability index model for the Andean catfish Astroblepus ubidiai (Pisces: Siluriformes) in Ecuador.

    PubMed

    Vélez-Espino, Luis A

    2006-06-01

    In conservation biology there is a basic need to determine habitat suitability and availability. Astroblepus ubidiai (Siluriforms), the only native fish in the highlands of Imbabura province in the Ecuadorian Andes, was abundant in the past in the Imbakucha watershed and adjacent drainages, but currently it is restricted to a few isolated refuges. Conservation actions are needed if this unique fish is to persist. A Habitat Suitability Index (HSI) for the species has been developed in order to aid management decisions. In this HSI model biomass density (B) was selected as a better indicator of habitat quality than either abundance or density. A population well-being index (PI) was constructed with the combination of B and an indicator of fish health (proportion of fish in the population with parasites and deformities). Based in other models of benthic fish the habitat variables current velocity, flow, depth, width, cover, invertebrate composition, vegetation type, terrestrial vegetation, land use, substrate, temperature, pH, TDS, oxygen, altitude, and slope were included in the analysis. An anthropogenic perturbation index (H) and a fragment isolation index (FII) were developed and included as habitat variables as well. The HSI model was applied to refuges and a sample of 15 aquatic bodies without fish populations within the study region. From the sampled sites without A. ubidiai 26.6% presented low quality, and the remaining 73.3% had medium quality according to the HSI estimated. Good quality habitat for dispersal, escape or translocations is rare in the region. The low HSIs estimated in some of the refuges suggests that current populations are not settled in the most favorable habitat but in the habitat least favorable to the agents of decline.

  9. A new genus and species of proteocephalidean (Cestoda) from Clarias catfishes (Siluriformes: Clariidae) in Africa.

    PubMed

    de Chambrier, Alain; Scholz, Tomás; Beletew, Moges; Mariaux, Jean

    2009-02-01

    A new proteocephalidean cestode is described from 2 catfishes, Clarias gariepinus (type host) and C. cf. anguillaris (Siluriformes: Clariidae), from Ethiopia (type locality), Sudan, Tanzania, and Zimbabwe, and a new genus, Barsonella, is proposed to accommodate it. The genus belongs to the Proteocephalinae because its genital organs (testes, ovary, vitellarium, and uterus) are situated in the medulla. Barsonella lafoni, the type and only species of the new genus, is characterized mainly by the possession of an additional opening of each sucker; circular musculature on the anterior margin of suckers, serving as a sphincter; a small thin-walled glandular apical organ; absence of well-developed osmoregulatory canals in mature, pregravid, and gravid proglottids; and a large strobila, up to 173 mm long and 3.2 mm wide. Species of Marsypocephalus Wedl, 1861 (Marsypocephalinae), other large-sized proteocephalidean tapeworms occurring sympatrically in African catfishes (Clarias and Heterobranchus) and also possessing a sphincter-like, circular musculature on the anterior part of suckers, differ from B. lafoni in the absence of an additional sucker opening and glandular apical organ, the cortical position of the testes, well-developed osmoregulatory canals throughout the strobila, and a large cirrus sac. Proteocephalus glanduligerus (Janicki, 1928), another cestode parasitic in Clarias spp. in Africa, is much smaller than B. lafoni (maximum length 15 mm), has suckers without additional opening and circular musculature on the suckers, a large-sized glandular organ, much larger than suckers, and well-developed osmoregulatory canals. Comparison of partial sequences of the 28S rRNA gene for 7 samples of B. lafoni from 2 different hosts and 4 localities in Ethiopia, Sudan, and Tanzania has shown a very low genetic variability. In a limited phylogenetic analysis, B. lafoni formed a clade with Corallobothrium solidum Fritsch, 1886 (Proteocephalidae: Corallobothriinae), an African

  10. 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.

  11. Comparative morphology of the gas bladder in driftwood catfishes (Siluriformes: Auchenipteridae).

    PubMed

    Birindelli, José L O; Akama, Alberto; Britski, Heraldo A

    2012-06-01

    The gross morphology of the gas bladder is described and illustrated for representatives of most species and all valid genera of the Auchenipteridae (Siluriformes). Although, a simple cordiform gas bladder is present in some species of the family, others are characterized by their distinctive gas-bladder shape and diverticula disposition. An acute posterior end of the gas bladder characterizes Centromochlus heckelii and C. macracanthus, and is variably present in specimens of Auchenipterus. Tocantinsia piresi and Asterophysus batrachus have distinctive gas bladders differing in number of diverticula (two or many). The two species of Trachycorystes are diagnosed based on their gas bladder morphology: T. menezesi has a simple cordiform bladder, whereas T. trachycorystes has a pair of lateral diverticulum and, usually, a well-developed terminal diverticulum. Species of Auchenipterichthys are characterized by having a secondary bladder with simple chamber. Short or elongate and divergent terminal diverticula are exclusive to most cis-andine species of Trachelyopterus. Tetranematichthys and trans-andine species of Trachelyopterus share a well-developed secondary chamber or terminal diverticula ventrally or dorsally connected to the posterior chambers. The small-sized species of Ageneiosus have well-developed gas bladders with a pair of posterior diverticula, whereas large-sized species have a reduced gas bladder with tunica externa varying from non-, partially, or completely ossified. Eight phylogenetic characters are proposed based on the morphology of the gas bladder and associated structures in species of Auchenipteridae, and the evolution of those characters in the family discussed. Copyright © 2011 Wiley Periodicals, Inc.

  12. 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

  13. 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

  14. 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

  15. In vitro culture of stress erythroid progenitors identifies distinct progenitor populations and analogous human progenitors

    PubMed Central

    Xiang, Jie; Wu, Dai-Chen; Chen, Yuanting

    2015-01-01

    Tissue hypoxia induces a systemic response designed to increase oxygen delivery to tissues. One component of this response is increased erythropoiesis. Steady-state erythropoiesis is primarily homeostatic, producing new erythrocytes to replace old erythrocytes removed from circulation by the spleen. In response to anemia, the situation is different. New erythrocytes must be rapidly made to increase hemoglobin levels. At these times, stress erythropoiesis predominates. Stress erythropoiesis is best characterized in the mouse, where it is extramedullary and utilizes progenitors and signals that are distinct from steady-state erythropoiesis. In this report, we use an in vitro culture system that recapitulates the in vivo development of stress erythroid progenitors. We identify cell-surface markers that delineate a series of stress erythroid progenitors with increasing maturity. In addition, we use this in vitro culture system to expand human stress erythroid progenitor cells that express analogous cell-surface markers. Consistent with previous suggestions that human stress erythropoiesis is similar to fetal erythropoiesis, we demonstrate that human stress erythroid progenitors express fetal hemoglobin upon differentiation. These data demonstrate that similar to murine bone marrow, human bone marrow contains cells that can generate BMP4-dependent stress erythroid burst-forming units when cultured under stress erythropoiesis conditions. PMID:25608563

  16. 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.

  17. Gamma-Ray Burst Progenitors

    NASA Astrophysics Data System (ADS)

    Levan, Andrew; Crowther, Paul; de Grijs, Richard; Langer, Norbert; Xu, Dong; Yoon, Sung-Chul

    2016-12-01

    We review our current understanding of the progenitors of both long and short duration gamma-ray bursts (GRBs). Constraints can be derived from multiple directions, and we use three distinct strands; (i) direct observations of GRBs and their host galaxies, (ii) parameters derived from modelling, both via population synthesis and direct numerical simulation and (iii) our understanding of plausible analog progenitor systems observed in the local Universe. From these joint constraints, we describe the likely routes that can drive massive stars to the creation of long GRBs, and our best estimates of the scenarios that can create compact object binaries which will ultimately form short GRBs, as well as the associated rates of both long and short GRBs. We further discuss how different the progenitors may be in the case of black hole engine or millisecond-magnetar models for the production of GRBs, and how central engines may provide a unifying theme between many classes of extremely luminous transient, from luminous and super-luminous supernovae to long and short GRBs.

  18. Modeling Renal Progenitors – Defining the Niche

    PubMed Central

    Tanigawa, Shunsuke; Perantoni, Alan O.

    2016-01-01

    Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for sustaining those progenitors have dramatically enhanced our understanding of their biology and developmental programing, prerequisites for establishing viable approaches to renal regeneration. In this article, we review the evolution of culture techniques and models for the study of metanephric development, describe the signaling mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+ progenitor. PMID:26856661

  19. Morphology and molecular characterization of Demidospermus spirophallus n. sp., D. prolixus n. sp. (Monogenea: Dactylogyridae) and a redescription of D. anus in siluriform catfish from Brazil.

    PubMed

    Franceschini, L; Zago, A C; Müller, M I; Francisco, C J; Takemoto, R M; da Silva, R J

    2017-04-06

    The present study describes Demidospermus spirophallus n. sp. and Demidospermus prolixus n. sp. (Monogenea, Dactylogyridae) from the siluriform catfish Loricaria prolixa Isbrücker & Nijssen, 1978 (Siluriformes, Loricariidae) from the state of São Paulo, Brazil, supported by morphological and molecular data. In addition, notes on the circumscription of the genus with a redescription of Demisdospermus anus are presented. Demidospermus spirophallus n. sp. differed from other congeners mainly because of the morphology of the male copulatory organ (MCO), which exhibited 2½ counterclockwise rings, a tubular accessory piece with one bifurcated end and a weakly sclerotized vagina with sinistral opening. Demidospermus prolixus n. sp. presents a counterclockwise-coiled MCO with 1½ rings, an ovate base, a non-articulated groove-like accessory piece serving as an MCO guide, two different hook shapes, inconspicuous tegumental annulations, a non-sclerotized vagina with sinistral opening and the absence of eyes or accessory eyespots. The present study provides, for the first time, molecular characterization data using the partial ribosomal gene (28S) of two new species of Demidospermus from Brazil (D. spirophallus n. sp. and D. prolixus n. sp.), and Demidospermus anus from Loricariichthys platymetopon Isbrücker & Nijssen, 1979 collected in the Upper Paraná River floodplain, Brazil. Additionally, a revision of the species composition of this genus and others that occur in catfish is proposed to elucidate problems with their circumscription. The Brazilian species of Demidospermus clustered together as sister taxa among Neotropical dactylogyrids from siluriforms. The morphological characterization of D. spirophallus n. sp. and D. prolixus n. sp., and the molecular data of the three species in the present study will extend knowledge about this monogenean genus from the Neotropical region, and provide new information for future phylogeny studies.

  20. Endothelial progenitor cells in atherosclerosis

    PubMed Central

    Du, Fuyong; Zhou, Jun; Gong, Ren; Huang, Xiao; Pansuria, Meghana; Virtue, Anthony; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs’ population and improvement of vascular function. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we provide a comprehensive overview on EPC characteristics, phenotypes, and the signaling pathways underlying EPC impairment in atherosclerosis. PMID:22652782

  1. Comparative morphology of the gonadal structure related to reproductive strategies in six species of neotropical catfishes (Teleostei: Siluriformes).

    PubMed

    Melo, Rafael Magno Costa; Arantes, Fábio Pereira; Sato, Yoshimi; dos Santos, José Enemir; Rizzo, Elizete; Bazzoli, Nilo

    2011-05-01

    We studied the relationship between the morphology of the reproductive system and the reproductive strategies of six neotropical catfishes using macroscopic and microscopic analyses. The reproductive system of the examined Siluriformes showed diversified characteristics, but permitted their being grouped according to three reproductive strategies: pelagic spawning, demersal spawning, and internally fertilizing. The pelagic spawners Pseudoplatystoma corruscans and Conorhynchos conirostris have testes that are characterized by filiform lobes, absence of testicular secretion, full-grown oocytes of small diameter, thin zona radiata, and cuboidal follicular cells. Pimelodus maculatus is morphologically distinct from the other two pelagic spawners catfishes due to the presence of testicular secretion. The demersal spawners Lophiosilurus alexandri and Rhinelepis aspera possess homogeneous testicular secretion, large mature oocytes, and columnar follicular cells. The most specialized reproductive system was observed in the internally fertilizing Trachelyopterus galeatus, which possesses a seminal vesicle accessory to the testes, spermatozoa with elongated nuclei that form spermatozeugmata, and a secretory ovarian lamellar epithelium that is associated with sperm storage. The reproductive system observed in Neotropical catfishes showed a relationship associated with the type of fertilization and the reproductive strategies of the six species studied. Copyright © 2011 Wiley-Liss, Inc.

  2. A new genus and species of proteocephalidean tapeworm (Cestoda) from Pangasius larnaudii (Siluriformes: Pangasiidae) in Southeast Asia.

    PubMed

    Scholz, Tomáš; de Chambrier, Alain

    2012-06-01

    A new proteocephalidean cestode is described from spot pangasius, Pangasius larnaudii (Siluriformes: Pangasiidae), from Tonle Sap Lake in Cambodia and a new genus, Pangasiocestus , is proposed to accommodate it. The genus is placed in the Gangesiinae because its scolex possesses a large rostellum-like apical organ and its genital organs (testes, ovary, vitellarium, and uterus) are situated in the medulla, with some vitelline follicles paramuscular. Pangasiocestus romani n. gen. and n. sp., the type and only species of the new genus, is characterized mainly by its rosette-like scolex composed of 4 lobes bearing a small sucker in their center, and the apical part with a large, discoidal, rostellum-like apical organ devoid of hooks, by weakly developed inner longitudinal musculature formed by very few isolated muscle fibers, uneven size of testes in immature and mature proglottids, with lateral testes smaller and more dense than median ones, by very narrow lateral bands of vitelline follicles, formed usually by single follicles, and by the vagina anterior to the cirrus sac. This is the first proteocephalidean cestode from a pangasiid catfish identified to the species level (proteocephalidean cestodes from 3 Pangasius spp. reported in an unpublished account from Vietnam, misidentified as Proteocephalus osculatus (Goeze, 1782) [ =  Glanitaenia osculata ], are not considered).

  3. Metazoan parasites of Conorhynchos conirostris (Valenciennes, 1840) an endemic siluriform fish of the São Francisco basin, Brazil.

    PubMed

    Brasil-Sato, Marilia de C; Dos Santos, Michelle D

    2005-01-01

    Specimens of Conorhynchos conirostris (Valenciennes, 1840) (Osteichthyes: Siluriformes) were collected from the upper São Francisco River (18 degrees 12'32''S, 45 degrees 15'41''W) in the municipality of Três Marias, Minas Gerais, Brazil, to investigate their parasitofauna. Of the 24 pirá fish collected, 8 were male (33.3%) and 16 were female (66.7%). Of this total, 12 were parasitized (50%). Nine species of parasites were found: Helobdella sp., Creptotrema creptotrema Travassos, Artigas & Pereira, 1928; Palaeocryptogonimus claviformis Szidat, 1954; metacercariae of Clinostomum sp. and of Austrodiplostomum compactum (Lutz 1928); Procamallanus (Spirocamallanus) sp. (young specimen); larvae of Anisakidae and Rhabdochona sp.; and Neoechinorhynchus sp. (young specimen). Helobdella sp. had the highest prevalence, followed by C. creptotrema (most abundant) and P. claviformis. Creptotrema creptotrema was dominant species in the parasite community of C. conirostris. There was no influence of the host size and sex on the prevalence and abundance of parasites, with P. claviformis being found only in male hosts. With the exception of Procamallanus (Spirocamallanus) sp., this was the first record of these parasites in C. conirostris.

  4. Progenitors of Supernovae Type Ia

    NASA Astrophysics Data System (ADS)

    Toonen, S.; Nelemans, G.; Bours, M.; Portegies Zwart, S.; Claeys, J.; Mennekens, N.; Ruiter, A.

    2013-01-01

    Despite the significance of Type Ia supernovae (SNeIa) in many fields in astrophysics, SNeIa lack a theoretical explanation. The standard scenarios involve thermonuclear explosions of carbon/oxygen white dwarfs approaching the Chandrasekhar mass; either by accretion from a companion or by a merger of two white dwarfs. We investigate the contribution from both channels to the SNIa rate with the binary population synthesis (BPS) code SeBa in order to constrain binary processes such as the mass retention efficiency of WD accretion and common envelope evolution. We determine the theoretical rates and delay time distribution of SNIa progenitors and in particular study how assumptions affect the predicted rates.

  5. Red supergiants as supernova progenitors

    NASA Astrophysics Data System (ADS)

    Davies, Ben

    2017-09-01

    It is now well-established from pre-explosion imaging that red supergiants (RSGs) are the direct progenitors of Type-IIP supernovae. These images have been used to infer the physical properties of the exploding stars, yielding some surprising results. In particular, the differences between the observed and predicted mass spectrum has provided a challenge to our view of stellar evolutionary theory. However, turning what is typically a small number of pre-explosion photometric points into the physical quantities of stellar luminosity and mass requires a number of assumptions about the spectral appearance of RSGs, as well as their evolution in the last few years of life. Here I will review what we know about RSGs, with a few recent updates on how they look and how their appearance changes as they approach supernova. This article is part of the themed issue 'Bridging the gap: from massive stars to supernovae'.

  6. The interface between glial progenitors and gliomas

    PubMed Central

    Canoll, Peter

    2009-01-01

    The mammalian brain and spinal cord contain heterogeneous populations of cycling, immature cells. These include cells with stem cell-like properties as well as progenitors in various stages of early glial differentiation. This latter population is distributed widely throughout gray and white matter and numerically represents an extremely large cell pool. In this review, we discuss the possibility that the glial progenitors that populate the adult CNS are one source of gliomas. Indeed, the marker phenotypes, morphologies, and migratory properties of cells in gliomas strongly resemble glial progenitors in many ways. We review briefly some salient features of normal glial development and then examine the similarities and differences between normal progenitors and cells in gliomas, focusing on the phenotypic plasticity of glial progenitors and the responses to growth factors in promoting proliferation and migration of normal and glioma cells, and discussing known mutational changes in gliomas in the context of how these might affect the proliferative and migratory behaviors of progenitors. Finally, we will discuss the “cancer stem cell” hypothesis in light of the possibility that glial progenitors can generate gliomas. PMID:18784926

  7. Prorenin receptor is critical for nephron progenitors

    PubMed Central

    Song, Renfang; Preston, Graeme; Kidd, Laura; Bushnell, Daniel; Sims-Lucas, Sunder; Bates, Carlton M.; Yosypiv, Ihor V.

    2016-01-01

    Deficient nephrogenesis is the major factor contributing to renal hypoplasia defined as abnormally small kidneys. Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H+-ATPase. Global loss of PRR is lethal in mice and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. To circumvent lethality of the ubiquitous PRR mutation in mice and to determine the potential role of the PRR in nephrogenesis, we generated a mouse model with a conditional deletion of the PRR in Six2+ nephron progenitors and their epithelial derivatives (Six2PRR−/−). Targeted ablation of PRR in Six2+ nephron progenitors caused a marked decrease in the number of developing nephrons, small cystic kidneys and podocyte foot process effacement at birth, and early postnatal death. Reduced congenital nephron endowment resulted from premature depletion of nephron progenitor cell population due to impaired progenitor cell proliferation and loss of normal molecular inductive response to canonical Wnt/β-catenin signaling within the metanephric mesenchyme. At 2 months of age, heterozygous Six2PRR+/− mice exhibited focal glomerulosclerosis, decreased kidney function and massive proteinuria. Collectively, these findings demonstrate a cell-autonomous requirement for the PRR within nephron progenitors for progenitor maintenance, progression of nephrogenesis, normal kidney development and function. PMID:26658320

  8. 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.

  9. A genetic analysis of neural progenitor differentiation.

    PubMed

    Geschwind, D H; Ou, J; Easterday, M C; Dougherty, J D; Jackson, R L; Chen, Z; Antoine, H; Terskikh, A; Weissman, I L; Nelson, S F; Kornblum, H I

    2001-02-01

    Genetic mechanisms regulating CNS progenitor function and differentiation are not well understood. We have used microarrays derived from a representational difference analysis (RDA) subtraction in a heterogeneous stem cell culture system to systematically study the gene expression patterns of CNS progenitors. This analysis identified both known and novel genes enriched in progenitor cultures. In situ hybridization in a subset of clones demonstrated that many of these genes were expressed preferentially in germinal zones, some showing distinct ventricular or subventricular zone labeling. Several genes were also enriched in hematopoietic stem cells, suggesting an overlap of gene expression in neural and hematopoietic progenitors. This combination of methods demonstrates the power of using custom microarrays derived from RDA-subtracted libraries for both gene discovery and gene expression analysis in the central nervous system.

  10. Circulating Vascular Progenitor Cells in Moyamoya Disease

    PubMed Central

    Kang, Hyun-Seung; Wang, Kyu-Chang

    2015-01-01

    Various approaches have been attempted in translational moyamoya disease research. One promising material for modeling and treating this disease is vascular progenitor cells, which can be acquired and expanded from patient peripheral blood. These cells may provide a novel experimental model and enable us to obtain insights regarding moyamoya disease pathogenesis. We briefly present the recent accomplishments in regard to the studies of vascular progenitor cells in moyamoya disease. PMID:26180610

  11. Prorenin receptor is critical for nephron progenitors.

    PubMed

    Song, Renfang; Preston, Graeme; Kidd, Laura; Bushnell, Daniel; Sims-Lucas, Sunder; Bates, Carlton M; Yosypiv, Ihor V

    2016-01-15

    Deficient nephrogenesis is the major factor contributing to renal hypoplasia defined as abnormally small kidneys. Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H(+)-ATPase. Global loss of PRR is lethal in mice and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. To circumvent lethality of the ubiquitous PRR mutation in mice and to determine the potential role of the PRR in nephrogenesis, we generated a mouse model with a conditional deletion of the PRR in Six2(+) nephron progenitors and their epithelial derivatives (Six2(PRR-/-)). Targeted ablation of PRR in Six2(+) nephron progenitors caused a marked decrease in the number of developing nephrons, small cystic kidneys and podocyte foot process effacement at birth, and early postnatal death. Reduced congenital nephron endowment resulted from premature depletion of nephron progenitor cell population due to impaired progenitor cell proliferation and loss of normal molecular inductive response to canonical Wnt/β-catenin signaling within the metanephric mesenchyme. At 2 months of age, heterozygous Six2(PRR+/-) mice exhibited focal glomerulosclerosis, decreased kidney function and massive proteinuria. Collectively, these findings demonstrate a cell-autonomous requirement for the PRR within nephron progenitors for progenitor maintenance, progression of nephrogenesis, normal kidney development and function. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 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.

  13. The phylogenetic relationships among non-diplomystid catfishes as inferred from mitochondrial cytochrome b sequences; the search for the ictalurid sister taxon (Otophysi: Siluriformes).

    PubMed

    Hardman, Michael

    2005-12-01

    The relationships among families of catfishes are poorly understood and have yet to be the subject of a comprehensive investigation with molecular data. Existing phylogenetic hypotheses are based on morphological data and incompletely resolved. This study analyzed complete sequences of mitochondrial gene cytochrome b for 170 species from 29 of 33 extant families, and focused on the relationships of Ictaluridae to other catfishes. In addition to previous phylogenetic studies, the fossil record, paleogeography, biogeography, and distribution of extant catfish families collectively suggest the location (if extant) of the ictalurid sister taxon to be Northern or Eastern Asia. Of the extant catfishes currently native to this area and included in this analysis, parsimony and Bayesian likelihood analyses recovered Cranoglanis bouderius as the most proximal sister taxon of Ictaluridae. Seemingly, ictalurids and cranoglanidids represent another biogeographic component linking freshwater fishes of North America and eastern Asia, e.g., catostomids and paddlefishes. The results coupled with present-day catfish distributions and inferences from the fossil record collectively suggest the ancestor of Ictaluridae to have invaded freshwaters of North America at the close of the Cretaceous through northeastern Asia and northwestern North America. Other superfamilial nodes supported the results of previous phylogenetic studies of narrower taxonomic scope. Several novel relationships were recovered (including a clade composed of Pimelodidae, Pseudopimelodidae, and Heptapteridae) and these along with sources of systematic error are discussed. A broad sampling of Bagridae permitted an examination of intergeneric relationships within this family and in light of recent morphological and molecular studies.

  14. 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.

  15. Spinitectus aguapeiensis n. sp. (Nematoda: Cystidicolidae) from Pimelodella avanhandavae Eigenmann (Siluriformes: Heptapteridae) in the River Aguapeí, Upper Paraná River Basin, Brazil.

    PubMed

    Acosta, Aline Angelina; González-Solís, David; da Silva, Reinaldo José

    2017-07-01

    Nematodes belonging to Spinitectus Fourment, 1883 (Nematoda: Cystidicolidae) were found in the intestine of Pimelodella avanhandavae Eigenmann (Siluriformes: Heptapteridae) from the Aguapeí River, Brazil. They represent a new species, Spinitectus aguapeiensis n. sp., which differs morphologically from its congeners in the body length, the number of spinose rings, the location of the excretory pore, the number of precloacal papillae and the length of the spicules. The new species is the first South American species within the genus with a remarkably spirally coiled posterior extremity in males and the largest spicules. It is also the second species with the highest number of precloacal papillae and has unique shape of the small spicule. Spinitectus aguapeiensis n. sp. is the first helminth species found in P. avanhandavae, the fourth species of this genus recorded in the River Paraná Basin and the sixth species of Spinitectus in South America.

  16. Endothelial progenitor cells in cardiovascular diseases

    PubMed Central

    Lee, Poay Sian Sabrina; Poh, Kian Keong

    2014-01-01

    Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vasculogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk factors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardiovascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evaluate the challenges facing EPC research and how these may be overcome. PMID:25126384

  17. Transient nuclear Prospero induces neural progenitor quiescence.

    PubMed

    Lai, Sen-Lin; Doe, Chris Q

    2014-10-29

    Stem cells can self-renew, differentiate, or enter quiescence. Understanding how stem cells switch between these states is highly relevant for stem cell-based therapeutics. Drosophila neural progenitors (neuroblasts) have been an excellent model for studying self-renewal and differentiation, but quiescence remains poorly understood. In this study, we show that when neuroblasts enter quiescence, the differentiation factor Prospero is transiently detected in the neuroblast nucleus, followed by the establishment of a unique molecular profile lacking most progenitor and differentiation markers. The pulse of low level nuclear Prospero precedes entry into neuroblast quiescence even when the timing of quiescence is advanced or delayed by changing temporal identity factors. Furthermore, loss of Prospero prevents entry into quiescence, whereas a pulse of low level nuclear Prospero can drive proliferating larval neuroblasts into quiescence. We propose that Prospero levels distinguish three progenitor fates: absent for self-renewal, low for quiescence, and high for differentiation.

  18. Neuropeptides: developmental signals in placode progenitor formation.

    PubMed

    Lleras-Forero, Laura; Tambalo, Monica; Christophorou, Nicolas; Chambers, David; Houart, Corinne; Streit, Andrea

    2013-07-29

    Few families of signaling factors have been implicated in the control of development. Here, we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in both chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors, with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin, and both peptides regulate Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, predating a complex nervous system.

  19. THE AGES OF TYPE Ia SUPERNOVA PROGENITORS

    SciTech Connect

    Brandt, Timothy D.; Aubourg, Eric; Strauss, Michael A.; Tojeiro, Rita; Heavens, Alan; Jimenez, Raul

    2010-09-15

    Using light curves and host galaxy spectra of 101 Type Ia supernovae (SNe Ia) with redshift z {approx}< 0.3 from the Sloan Digital Sky Survey Supernova Survey (SDSS-SN), we derive the SN Ia rate as a function of progenitor age (the delay time distribution, DTD). We use the VESPA stellar population synthesis algorithm to analyze the SDSS spectra of all galaxies in the field searched by SDSS-SN, giving us a reference sample of 77,000 galaxies for our SN Ia hosts. Our method does not assume any a priori shape for the DTD and is therefore minimally parametric. We present the DTD in physical units for high-stretch (luminous, slow declining) and low-stretch (subluminous, fast declining) supernovae in three progenitor age bins. We find strong evidence of two progenitor channels: one that produces high-stretch SNe Ia {approx}<400 Myr after the birth of the progenitor system, and one that produces low-stretch SNe Ia with a delay {approx}>2.4 Gyr. We find that each channel contributes roughly half of the Type Ia rate in our reference sample. We also construct the average spectra of high-stretch and low-stretch SN Ia host galaxies, and find that the difference of these spectra looks like a main-sequence B star with nebular emission lines indicative of star formation. This supports our finding that there are two populations of SNe Ia, and indicates that the progenitors of high-stretch supernovae are at the least associated with very recent star formation in the last few tens of Myr. Our results provide valuable constraints for models of Type Ia progenitors and may help improve the calibration of SNe Ia as standard candles.

  20. Single Degenerate Progenitors of Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Bours, Madelon; Toonen, Silvia; Nelemans, Gijs

    2013-01-01

    There is a general agreement that Type Ia supernovae correspond to the thermonuclear runaway of a white dwarf (WD) in a compact binary. The details of these progenitor systems are still unclear. Using the population synthesis code SeBa and several assumption for the WD retention efficiency, we estimate the delay times and supernova rates for the single degenerate scenario.

  1. Direct Conversion of Fibroblasts to Megakaryocyte Progenitors.

    PubMed

    Pulecio, Julian; Alejo-Valle, Oriol; Capellera-Garcia, Sandra; Vitaloni, Marianna; Rio, Paula; Mejía-Ramírez, Eva; Caserta, Ilaria; Bueren, Juan A; Flygare, Johan; Raya, Angel

    2016-10-11

    Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41(+), display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.

  2. The Progenitors of Type Ia Supernova

    NASA Astrophysics Data System (ADS)

    Tout, C. A.

    2005-08-01

    Type Ia supernovae are identified as exploding degenerate stars. Their luminosity is due to the radioactive decay of about a solar mass of 56Ni through 56Co to 56Fe. As such they are a major source of iron in the inter-stellar medium. Although it is generally accepted that a degenerate carbon/oxygen white dwarf explodes as it accretes material from a binary companion, the progenitors of type Ia supernovae have not been categorically identified. We discuss the various possible progenitors in detail and indicate theoretical and observational difficulties with each possibility. It may well be that the true nature of the progenitors has not yet even been conceived of. We look at why population synthesis fails to help distinguish and consider how the advent of population nucleosynthesis may change this. When used as universal standard candles SNe Ia are calibrated with the Phillips relation between absolute luminosity and light curve shape. This must therefore be valid at all redshifts and so both the absolute luminosity and the light curve decay must only depend on a single major property of the progenitors. We report on the latest understanding of this relation and find little to justify its universality beyond the local empirical evidence. A major effect on the absolute luminosities is the neutron to proton ratio at the time of the explosion because this determines the fraction of iron group elements made up of 56Ni.

  3. Targeting human oligodendrocyte progenitors for myelin repair.

    PubMed

    Dietz, Karen C; Polanco, Jessie J; Pol, Suyog U; Sim, Fraser J

    2016-09-01

    Oligodendrocyte development has been studied for several decades, and has served as a model system for both neurodevelopmental and stem/progenitor cell biology. Until recently, the vast majority of studies have been conducted in lower species, especially those focused on rodent development and remyelination. In humans, the process of myelination requires the generation of vastly more myelinating glia, occurring over a period of years rather than weeks. Furthermore, as evidenced by the presence of chronic demyelination in a variety of human neurologic diseases, it appears likely that the mechanisms that regulate development and become dysfunctional in disease may be, in key ways, divergent across species. Improvements in isolation techniques, applied to primary human neural and oligodendrocyte progenitors from both fetal and adult brain, as well as advancements in the derivation of defined progenitors from human pluripotent stem cells, have begun to reveal the extent of both species-conserved signaling pathways and potential key differences at cellular and molecular levels. In this article, we will review the commonalities and differences in myelin development between rodents and man, describing the approaches used to study human oligodendrocyte differentiation and myelination, as well as heterogeneity within targetable progenitor pools, and discuss the advances made in determining which conserved pathways may be both modeled in rodents and translate into viable therapeutic strategies to promote myelin repair.

  4. 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

  5. Origin of hemopoietic stromal progenitor cells in chimeras

    SciTech Connect

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-12-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice.

  6. Galactic constraints on supernova progenitor models

    NASA Astrophysics Data System (ADS)

    Acharova, I. A.; Gibson, B. K.; Mishurov, Yu. N.; Kovtyukh, V. V.

    2013-09-01

    Aims: To estimate the mean masses of oxygen and iron ejected per each type of supernovae (SNe) event from observations of the elemental abundance patterns in the Galactic disk and constrain the relevant SNe progenitor models. Methods: We undertake a statistical analysis of the radial abundance distributions in the Galactic disk within a theoretical framework for Galactic chemical evolution which incorporates the influence of spiral arms. This framework has been shown to recover the non-linear behaviour in radial gradients, the mean masses of oxygen and iron ejected during SNe explosions to be estimated, and constraints to be placed on SNe progenitor models. Results: (i) The mean mass of oxygen ejected per core-collapse SNe (CC SNe) event (which are concentrated within spiral arms) is ~0.27 M⊙; (ii) the mean mass of iron ejected by tardy Type Ia SNe (SNeIa, whose progenitors are older/longer-lived stars with ages ≳100 Myr and up to several Gyr, which do not concentrate within spiral arms) is ~0.58 M⊙; (iii) the upper mass of iron ejected by prompt SNeIa (SNe whose progenitors are younger/shorter-lived stars with ages ≲100 Myr, which are concentrated within spiral arms) is ≤0.23 M⊙ per event; (iv) the corresponding mean mass of iron produced by CC SNe is ≤0.04 M⊙ per event; (v) short-lived SNe (core-collapse or prompt SNeIa) supply ~85% of the Galactic disk's iron. Conclusions: The inferred low mean mass of oxygen ejected per CC SNe event implies a low upper mass limit for the corresponding progenitors of ~23 M⊙, otherwise the Galactic disk would be overabundant in oxygen. This inference is the consequence of the non-linear dependence between the upper limit of the progenitor initial mass and the mean mass of oxygen ejected per CC SNe explosion. The low mean mass of iron ejected by prompt SNeIa, relative to the mass produced by tardy SNeIa (~2.5 times lower), prejudices the idea that both sub-populations of SNeIa have the same physical nature. We

  7. New therapy targeting differential androgen receptor signaling in prostate cancer stem/progenitor vs. non-stem/progenitor cells

    PubMed Central

    Lee, Soo Ok; Ma, Zhifang; Yeh, Chiuan-Ren; Luo, Jie; Lin, Tzu-Hua; Lai, Kuo-Pao; Yamashita, Shinichi; Liang, Liang; Tian, Jing; Li, Lei; Jiang, Qi; Huang, Chiung-Kuei; Niu, Yuanjie; Yeh, Shuyuan; Chang, Chawnshang

    2013-01-01

    The androgen deprivation therapy (ADT) to systematically suppress/reduce androgens binding to the androgen receptor (AR) has been the standard therapy for prostate cancer (PCa); yet, most of ADT eventually fails leading to the recurrence of castration resistant PCa. Here, we found that the PCa patients who received ADT had increased PCa stem/progenitor cell population. The addition of the anti-androgen, Casodex®, or AR-siRNA in various PCa cells led to increased stem/progenitor cells, whereas, in contrast, the addition of functional AR led to decreased stem/progenitor cell population but increased non-stem/progenitor cell population, suggesting that AR functions differentially in PCa stem/progenitor vs. non-stem/progenitor cells. Therefore, the current ADT might result in an undesired expansion of PCa stem/progenitor cell population, which explains why this therapy fails. Using various human PCa cell lines and three different mouse models, we concluded that targeting PCa non-stem/progenitor cells with AR degradation enhancer ASC-J9® and targeting PCa stem/progenitor cells with 5-azathioprine and γ-tocotrienol resulted in a significant suppression of the tumors at the castration resistant stage. This suggests that a combinational therapy that simultaneously targets both stem/progenitor and non-stem/progenitor cells will lead to better therapeutic efficacy and may become a new therapy to battle the PCa before and after castration resistant stages. PMID:22831834

  8. Sall1 in renal stromal progenitors non-cell autonomously restricts the excessive expansion of nephron progenitors.

    PubMed

    Ohmori, Tomoko; Tanigawa, Shunsuke; Kaku, Yusuke; Fujimura, Sayoko; Nishinakamura, Ryuichi

    2015-10-29

    The mammalian kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud, the former of which contains nephron progenitors. The third lineage, the stroma, fills up the interstitial space and is derived from distinct progenitors that express the transcription factor Foxd1. We showed previously that deletion of the nuclear factor Sall1 in nephron progenitors leads to their depletion in mice. However, Sall1 is expressed not only in nephron progenitors but also in stromal progenitors. Here we report that specific Sall1 deletion in stromal progenitors leads to aberrant expansion of nephron progenitors, which is in sharp contrast with a nephron progenitor-specific deletion. The mutant mice also exhibited cystic kidneys after birth and died before adulthood. We found that Decorin, which inhibits Bmp-mediated nephron differentiation, was upregulated in the mutant stroma. In contrast, the expression of Fat4, which restricts nephron progenitor expansion, was reduced mildly. Furthermore, the Sall1 protein binds to many stroma-related gene loci, including Decorin and Fat4. Thus, the expression of Sall1 in stromal progenitors restricts the excessive expansion of nephron progenitors in a non-cell autonomous manner, and Sall1-mediated regulation of Decorin and Fat4 might at least partially underlie the pathogenesis.

  9. Sall1 in renal stromal progenitors non-cell autonomously restricts the excessive expansion of nephron progenitors

    PubMed Central

    Ohmori, Tomoko; Tanigawa, Shunsuke; Kaku, Yusuke; Fujimura, Sayoko; Nishinakamura, Ryuichi

    2015-01-01

    The mammalian kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud, the former of which contains nephron progenitors. The third lineage, the stroma, fills up the interstitial space and is derived from distinct progenitors that express the transcription factor Foxd1. We showed previously that deletion of the nuclear factor Sall1 in nephron progenitors leads to their depletion in mice. However, Sall1 is expressed not only in nephron progenitors but also in stromal progenitors. Here we report that specific Sall1 deletion in stromal progenitors leads to aberrant expansion of nephron progenitors, which is in sharp contrast with a nephron progenitor-specific deletion. The mutant mice also exhibited cystic kidneys after birth and died before adulthood. We found that Decorin, which inhibits Bmp-mediated nephron differentiation, was upregulated in the mutant stroma. In contrast, the expression of Fat4, which restricts nephron progenitor expansion, was reduced mildly. Furthermore, the Sall1 protein binds to many stroma-related gene loci, including Decorin and Fat4. Thus, the expression of Sall1 in stromal progenitors restricts the excessive expansion of nephron progenitors in a non-cell autonomous manner, and Sall1-mediated regulation of Decorin and Fat4 might at least partially underlie the pathogenesis. PMID:26511275

  10. 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

  11. Resident mesenchymal progenitors of articular cartilage.

    PubMed

    Candela, Maria Elena; Yasuhara, Rika; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2014-10-01

    Articular cartilage has poor capacity of self-renewal and repair. Insufficient number and activity of resident mesenchymal (connective tissue) progenitors is likely one of the underlying reasons. Chondroprogenitors reside not only in the superficial zone of articular cartilage but also in other zones of articular cartilage and in the neighboring tissues, including perichondrium (groove of Ranvier), synovium and fat pad. These cells may respond to injury and contribute to articular cartilage healing. In addition, marrow stromal cells can migrate through subchondral bone when articular cartilage is damaged. We should develop drugs and methods that correctly stimulate resident progenitors for improvement of repair and inhibition of degenerative changes in articular cartilage. Copyright © 2014. Published by Elsevier B.V.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Endothelial progenitor cell biology in ankylosing spondylitis.

    PubMed

    Verma, Inderjeet; Syngle, Ashit; Krishan, Pawan

    2015-03-01

    Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). EPCs were depleted in AS patients as compared to healthy controls (CD34(+) /CD133(+) : 0.027 ± 0.010% vs. 0.044 ± 0.011%, P < 0.001). EPC depletions were significantly associated with disease duration (r = -0.52, P = 0.01), BASDAI (r = -0.45, P = 0.04) and C-reactive protein (r = -0.5, P = 0.01). This is the first study to demonstrate endothelial progenitor cell depletion in AS patients. EPC depletions inversely correlate with disease duration, disease activity and inflammation, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  17. 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.

  18. Endothelial Progenitors: A Consensus Statement on Nomenclature.

    PubMed

    Medina, Reinhold J; Barber, Chad L; Sabatier, Florence; Dignat-George, Francoise; Melero-Martin, Juan M; Khosrotehrani, Kiarash; Ohneda, Osamu; Randi, Anna M; Chan, Jerry K Y; Yamaguchi, Teruhide; Van Hinsbergh, Victor W M; Yoder, Mervin C; Stitt, Alan W

    2017-03-10

    Endothelial progenitor cell (EPC) nomenclature remains ambiguous and there is a general lack of concordance in the stem cell field with many distinct cell subtypes continually grouped under the term "EPC." It would be highly advantageous to agree standards to confirm an endothelial progenitor phenotype and this should include detailed immunophenotyping, potency assays, and clear separation from hematopoietic angiogenic cells which are not endothelial progenitors. In this review, we seek to discourage the indiscriminate use of "EPCs," and instead propose precise terminology based on defining cellular phenotype and function. Endothelial colony forming cells and myeloid angiogenic cells are examples of two distinct and well-defined cell types that have been considered EPCs because they both promote vascular repair, albeit by completely different mechanisms of action. It is acknowledged that scientific nomenclature should be a dynamic process driven by technological and conceptual advances; ergo the ongoing "EPC" nomenclature ought not to be permanent and should become more precise in the light of strong scientific evidence. This is especially important as these cells become recognized for their role in vascular repair in health and disease; and, in some cases, progress toward use in cell therapy. © Stem Cells Translational Medicine 2017.

  19. Transient nuclear Prospero induces neural progenitor quiescence

    PubMed Central

    Lai, Sen-Lin; Doe, Chris Q

    2014-01-01

    Stem cells can self-renew, differentiate, or enter quiescence. Understanding how stem cells switch between these states is highly relevant for stem cell-based therapeutics. Drosophila neural progenitors (neuroblasts) have been an excellent model for studying self-renewal and differentiation, but quiescence remains poorly understood. In this study, we show that when neuroblasts enter quiescence, the differentiation factor Prospero is transiently detected in the neuroblast nucleus, followed by the establishment of a unique molecular profile lacking most progenitor and differentiation markers. The pulse of low level nuclear Prospero precedes entry into neuroblast quiescence even when the timing of quiescence is advanced or delayed by changing temporal identity factors. Furthermore, loss of Prospero prevents entry into quiescence, whereas a pulse of low level nuclear Prospero can drive proliferating larval neuroblasts into quiescence. We propose that Prospero levels distinguish three progenitor fates: absent for self-renewal, low for quiescence, and high for differentiation. DOI: http://dx.doi.org/10.7554/eLife.03363.001 PMID:25354199

  20. Adrenomedullary progenitor cells: Isolation and characterization of a multi-potent progenitor cell population.

    PubMed

    Vukicevic, Vladimir; Rubin de Celis, Maria Fernandez; Pellegata, Natalia S; Bornstein, Stefan R; Androutsellis-Theotokis, Andreas; Ehrhart-Bornstein, Monika

    2015-06-15

    The adrenal is a highly plastic organ with the ability to adjust to physiological needs by adapting hormone production but also by generating and regenerating both adrenocortical and adrenomedullary tissue. It is now apparent that many adult tissues maintain stem and progenitor cells that contribute to their maintenance and adaptation. Research from the last years has proven the existence of stem and progenitor cells also in the adult adrenal medulla throughout life. These cells maintain some neural crest properties and have the potential to differentiate to the endocrine and neural lineages. In this article, we discuss the evidence for the existence of adrenomedullary multi potent progenitor cells, their isolation and characterization, their differentiation potential as well as their clinical potential in transplantation therapies but also in pathophysiology.

  1. Regulation of the nascent brain vascular network by neural progenitors.

    PubMed

    Santhosh, Devi; Huang, Zhen

    2015-11-01

    Neural progenitors are central players in the development of the brain neural circuitry. They not only produce the diverse neuronal and glial cell types in the brain, but also guide their migration in this process. Recent evidence indicates that neural progenitors also play a critical role in the development of the brain vascular network. At an early stage, neural progenitors have been found to facilitate the ingression of blood vessels from outside the neural tube, through VEGF and canonical Wnt signaling. Subsequently, neural progenitors directly communicate with endothelial cells to stabilize nascent brain vessels, in part through down-regulating Wnt pathway activity. Furthermore, neural progenitors promote nascent brain vessel integrity, through integrin αvβ8-dependent TGFβ signaling. In this review, we will discuss the evidence for, as well as questions that remain, regarding these novel roles of neural progenitors and the underlying mechanisms in their regulation of the nascent brain vascular network.

  2. Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation

    PubMed Central

    Kopko, Patricia M.

    2016-01-01

    Summary ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell transplants. Major, minor and bidirectional ABO-incompatible transplants each have unique complications that can occur, including hemolysis at the time of progenitor cell infusion, hemolysis during donor engraftment, passenger lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell aplasia. Appropriate transfusion support during the different phases of the allogeneic progenitor cell transplant process is an important part of ABO-incompatible transplantation. PMID:27022318

  3. 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

  4. CD133+ Renal Progenitor Cells Contribute to Tumor Angiogenesis

    PubMed Central

    Bruno, Stefania; Bussolati, Benedetta; Grange, Cristina; Collino, Federica; Efrem Graziano, Manuela; Ferrando, Ugo; Camussi, Giovanni

    2006-01-01

    In the present study, we tested the hypothesis that resident progenitor cells may contribute to tumor vascularization and growth. CD133+ cells were isolated from 30 human renal carcinomas and characterized as renal resident progenitor cells on the basis of the expression of renal embryonic and mesenchymal stem cell markers. CD133+ progenitors differentiated into endothelial and epithelial cells as the normal CD133+ counterpart present in renal tissue. In the presence of tumor-derived growth factors, these cells were committed to differentiate into endothelial cells able to form vessels in vivo in SCID mice. Undifferentiated CD133+ progenitors were unable to form tumors when transplanted alone in SCID mice. When co-transplanted with renal carcinoma cells, CD133+ progenitors significantly enhanced tumor development and growth. This effect was not attributable to the tumorigenic nature of CD133+ progenitor cells because the same results were obtained with CD133+ cells from normal kidney. CD133+ progenitors contributed to tumor vascularization as the majority of neoformed vessels present within the transplanted tumors were of human origin and derived from the co-transplanted CD133+ progenitors. In conclusion, these results indicate the presence of a renal progenitor cell population in renal carcinomas that may differentiate in endothelial cells and favor vascularization and tumor growth. PMID:17148683

  5. 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

  6. Progenitor Cells in Proximal Airway Epithelial Development and Regeneration

    PubMed Central

    Lynch, Thomas J.; Engelhardt, John F.

    2015-01-01

    Multiple distinct epithelial domains are found throughout the airway that are distinguishable by location, structure, function, and cell-type composition. Several progenitor cell populations in the proximal airway have been identified to reside in confined microenvironmental niches including the submucosal glands (SMGs), which are embedded in the tracheal connective tissue between the surface epithelium and cartilage, and basal cells that reside within the surface airway epithelium (SAE). Current research suggests that regulatory pathways that coordinate development of the proximal airway and establishment of progenitor cell niches may overlap with pathways that control progenitor cell responses during airway regeneration following injury. SMGs have been shown to harbor epithelial progenitor cells, and this niche is dysregulated in diseases such as cystic fibrosis. However, mechanisms that regulate progenitor cell proliferation and maintenance within this glandular niche are not completely understood. Here we discuss glandular progenitor cells during development and regeneration of the proximal airway and compare properties of glandular progenitors to those of basal cell progenitors in the SAE. Further investigation into glandular progenitor cell control will provide a direction for interrogating therapeutic interventions to correct aberrant conditions affecting the SMGs in diseases such as cystic fibrosis, chronic bronchitis, and asthma. PMID:24818588

  7. The Laterosensory Canal System in Epigean and Subterranean Ituglanis (Siluriformes: Trichomycteridae), With Comments About Troglomorphism and the Phylogeny of the Genus.

    PubMed

    Rizzato, Pedro Pereira; Bichuette, Maria Elina

    2017-01-01

    The laterosensory system is a mechanosensory modality involved in many aspects of fish biology and behavior. Laterosensory perception may be crucial for individual survival, especially in habitats where other sensory modalities are generally useless, such as the permanently aphotic subterranean environment. In the present study, we describe the laterosensory canal system of epigean and subterranean species of the genus Ituglanis (Siluriformes: Trichomycteridae). With seven independent colonizations of the subterranean environment in a limited geographical range coupled with a high diversity of epigean forms, the genus is an excellent model for the study of morphological specialization to hypogean life. The comparison between epigean and subterranean species reveals a trend toward reduction of the laterosensory canal system in the subterranean species, coupled with higher intraspecific variability and asymmetry. This trend is mirrored in other subterranean fishes and in species living in different confined spaces, like the interstitial environment. Therefore, we propose that the reduction of the laterosensory canal system should be regarded as a troglomorphic (= cave-related) character for subterranean fishes. We also comment about the patterns of the laterosensory canal system in trichomycterids and use the diversity of this system among species of Ituglanis to infer phylogenetic relationships within the genus. J. Morphol. 278:4-28, 2017. ©© 2016 Wiley Periodicals,Inc.

  8. Population Dynamics and Diet of the Madamango Sea Catfish Cathorops spixii (Agassiz, 1829) (Siluriformes: Ariidae) in a Tropical Bight in Southeastern Brazil

    PubMed Central

    Denadai, Márcia; Pombo, Maíra; Santos, Flávia Borges; Bessa, Eduardo; Ferreira, Adriana; Turra, Alexander

    2013-01-01

    The madamango sea catfish, Cathorops spixii (Siluriformes: Ariidae), is often among the most abundant fishes on the South American Atlantic coast. In the present study, conducted in shallow, non-estuarine coastal areas of Caraguatatuba Bight in southeastern Brazil, collections of this species, the most abundant member of the ichthyofauna, included primarily medium-sized individuals, indicating that the area may play a specific role in their development. Although studies of the local ichthyofauna have been much neglected, the area is economically important and its ecological significance is undervalued. This study primarily treats habitat use by C. spixii, assessing certain population parameters and the dietary composition. Monthly samples were taken from August 2003 through October 2004, with three trawls in two areas, corresponding to depths of about 1 to 4 m. The catfish showed two main peaks of abundance in the area, in April/May and July 2004. A mode around 9 cm SL persisted through time, and the entrance of younger recruits peaked from January to April. The low estimate for body-growth parameters (K = 0.16) corroborates some K-strategist characteristics of the species. The asymptotic length was 27.3 cm SL and total mortality (Z) was 1.01 yr−1. Cathorops spixii showed an omnivorous feeding habit, preying mainly upon polychaetes, copepods and bivalves, with considerable seasonality in its diet. PMID:24282575

  9. 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.

  10. Blood flukes (Digenea: Aporocotylidae) of walking catfishes (Siluriformes: Clariidae): new genus and species from the Mekong River (Vietnam) with comments on related catfish aporocotylids.

    PubMed

    Truong, Triet Nhat; Bullard, Stephen A

    2013-07-01

    Nomasanguinicola canthoensis gen. et sp. n. infects the branchial vessels of bighead catfish, Clarias macrocephalus Günther (Siluriformes: Clariidae), in the Mekong River near Can Tho, southern Vietnam. Nomasanguinicola differs from all other genera of fish blood flukes (Digenea: Aporocotylidae) by the combination of lacking body spines and by having an anterior sucker with two flanking columns of large denticles, an intestine comprising several short papilla-like caeca, an inverse U-shaped uterus, and an ootype located near the separate genital pores. The new species has an ootype that is posterior to the level of the female genital pore. That feature most easily differentiates it from the only other putative aporocotylid species having an anterior sucker with two flanking columns of large denticles, Plehniella dentata Paperna, 1964 and Sanguinicola clarias Imam, Marzouk, Hassan et Itman, 1984, which have an ootype that is lateral (P. dentata) or anterior (S. clarias) to the level of the female genital pore. These two species apparently lack extant type materials, infect North African catfish, Clarias gariepinus (Burchell), and herein are considered incertae sedis, but likely comprise species of Nomasanguinicola. An updated list of hosts, sites of infection and geographic localities for the six species and three genera of blood flukes that mature in catfishes is provided. The new species is the first fish blood fluke recorded from Vietnam and only the third reported from a walking catfish (Clariidae).

  11. A large-scale phylogeny of Synodontis (Mochokidae, Siluriformes) reveals the influence of geological events on continental diversity during the Cenozoic.

    PubMed

    Pinton, Aurélie; Agnèse, Jean-François; Paugy, Didier; Otero, Olga

    2013-03-01

    To explain the spatial variability of fish taxa at a large scale, two alternative proposals are usually evoked. In recent years, the debate has centred on the relative roles of present and historical processes in shaping biodiversity patterns. In Africa, attempts to understand the processes that determine the large scale distribution of fishes and exploration of historical contingencies have been under-investigated given that most of the phylogenetic studies focus on the history of the Great Lakes. Here, we explore phylogeographic events in the evolutionary history of Synodontis (Mohokidae, Siluriformes) over Africa during the Cenozoic focusing on the putative role of historical processes. We discuss how known geological events together with hydrographical changes contributed to shape Synodontis biogeographical history. Synodontis was chosen on the basis of its high diversity and distribution in Africa: it consists of approximately 120 species that are widely distributed in all hydrographic basins except the Maghreb and South Africa. We propose the most comprehensive phylogeny of this catfish genus. Our results provide support for the 'hydrogeological' hypothesis, which proposes that palaeohydrological changes linked with the geological context may have been the cause of diversification of freshwater fish deep in the Tertiary. More precisely, the two main geological structures that participated to shape the hydrographical network in Africa, namely the Central African Shear zone and the East African rift system, appear as strong drivers of Synodontis diversification and evolution. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 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.

  13. Ethanol induces cytostasis of cortical basal progenitors.

    PubMed

    Riar, Amanjot Kaur; Narasimhan, Madhusudhanan; Rathinam, Mary Latha; Henderson, George I; Mahimainathan, Lenin

    2016-01-19

    Developing brain is a major target for alcohol's actions and neurological/functional abnormalities include microencephaly, reduced frontal cortex, mental retardation and attention-deficits. Previous studies have shown that ethanol altered the lateral ventricular neuroepithelial cell proliferation. However, the effect of ethanol on subventricular basal progenitors which generate majority of the cortical layers is not known. We utilized spontaneously immortalized rat brain neuroblasts obtained from cultures of 18-day-old fetal rat cerebral cortices using in vitro ethanol exposures and an in utero binge model. In the in vitro acute model, cells were exposed to 86 mM ethanol for 8, 12 and 24 h. The second in vitro model comprised of chronic intermittent ethanol (CIE) exposure which consisted of 14 h of ethanol treatment followed by 10 h of withdrawal with three repetitions. E18 neuroblasts expressing Tbr2 representing immature basal progenitors displayed significant reduction of proliferation in response to ethanol in both the models. The decreased proliferation was accompanied by absence of apoptosis or autophagy as illustrated by FACS analysis and expression of apoptotic and autophagic markers. The BrdU incorporation assay indicated that ethanol enhanced the accumulation of cells at G1 with reduced cell number in S phase. In addition, the ethanol-inhibited basal neuroblasts proliferation was connected to decrease in cyclin D1 and Rb phosphorylation indicating cell cycle arrest. Further, in utero ethanol exposure in pregnant rats during E15-E18 significantly decreased Tbr2 and cyclin D1 positive cell number in cerebral cortex of embryos as assessed by cell sorting analysis by flow cytometry. Altogether, the current findings demonstrate that ethanol impacts the expansion of basal progenitors by inducing cytostasis that might explain the anomalies of cortico-cerebral development associated with fetal alcohol syndrome.

  14. 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

  15. 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.

  16. 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.

  17. Defining and redefining the nephron progenitor population.

    PubMed

    Hendry, Caroline; Rumballe, Bree; Moritz, Karen; Little, Melissa H

    2011-09-01

    It has long been appreciated that the mammalian kidney arises via reciprocal interactions between an epithelial ureteric epithelium and the surrounding metanephric mesenchyme. More recently, lineage tracing has confirmed that the portion of the metanephric mesenchyme closest to the advancing ureteric tips, the cap mesenchyme, represents the progenitor population for the nephron epithelia. This Six2(+)Cited1(+) population undergoes self-renewal throughout nephrogenesis while retaining the potential to epithelialize. In contrast, the Foxd1(+) portion of the metanephric mesenchyme shows no epithelial potential, developing instead into the interstitial, perivascular, and possibly endothelial elements of the kidney. The cap mesenchyme rests within a nephrogenic niche, surrounded by the stroma and the ureteric tip. While the role of Wnt signaling in nephron induction is known, there remains a lack of clarity over the intrinsic and extrinsic regulation of cap mesenchyme specification, self-renewal, and nephron potential. It is also not known what regulates cessation of nephrogenesis, but there is no nephron generation in response to injury during the postnatal period. In this review, we will examine what is and is not known about this nephron progenitor population and discuss how an increased understanding of the regulation of this population may better explain the observed variation in final nephron number and potentially facilitate the reinitiation or prolongation of nephron formation.

  18. ENDOTHELIAL PROGENITOR CELLS: FROM SENESCENCE TO REJUVENATION

    PubMed Central

    Goligorsky, Michael S

    2014-01-01

    Discovered more than 15 years ago, endothelial progenitor cells attract both basic and translational researchers. It has become clear that they represent a heterogeneous population of endothelial colony forming cells, early or late outgrowth endothelial cells, or blood outgrowth endothelial cells, each characterized by differing proliferative and regenerative capacity. Scattered within the vascular wall, these cells participate in angiogenesis and vasculogenesis and support regeneration of epithelial cells. There is growing evidence that this cell population is impaired during the course of chronic cardiovascular and kidney disease when it undergoes premature senescence and loss of specialized functions. Senescence-associated secretory products released by such cells can affect the neighboring cells and further exacerbate their regenerative capacity. For those reasons adoptive transfer of endothelial progenitor cells is being used in more than 150 on-going clinical trials in diverse cardiovascular diseases. There is emergence of attempts to rejuvenate this cell population either ex vivo or in situ. The progress in this field is paramount to regenerate the injured kidney. PMID:25217265

  19. Endothelial progenitor cells: from senescence to rejuvenation.

    PubMed

    Goligorsky, Michael S

    2014-07-01

    Discovered more than 15 years ago, endothelial progenitor cells attract both basic and translational researchers. It has become clear that they represent a heterogeneous population of endothelial colony-forming cells, early or late outgrowth endothelial cells, or blood outgrowth endothelial cells, each characterized by differing proliferative and regenerative capacity. Scattered within the vascular wall, these cells participate in angiogenesis and vasculogenesis and support regeneration of epithelial cells. There is growing evidence that this cell population is impaired during the course of chronic cardiovascular and kidney disease when it undergoes premature senescence and loss of specialized functions. Senescence-associated secretory products released by such cells can affect the neighboring cells and further exacerbate their regenerative capacity. For these reasons, adoptive transfer of endothelial progenitor cells is being used in more than 150 ongoing clinical trials of diverse cardiovascular diseases. Attempts to rejuvenate this cell population either ex vivo or in situ are emerging. The progress in this field is paramount to regenerate the injured kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Predicting the nature of supernova progenitors

    NASA Astrophysics Data System (ADS)

    Groh, Jose H.

    2017-09-01

    Stars more massive than about 8 solar masses end their lives as a supernova (SN), an event of fundamental importance Universe-wide. The physical properties of massive stars before the SN event are very uncertain, both from theoretical and observational perspectives. In this article, I briefly review recent efforts to predict the nature of stars before death, in particular, by performing coupled stellar evolution and atmosphere modelling of single stars in the pre-SN stage. These models are able to predict the high-resolution spectrum and broadband photometry, which can then be directly compared with the observations of core-collapse SN progenitors. The predictions for the spectral types of massive stars before death can be surprising. Depending on the initial mass and rotation, single star models indicate that massive stars die as red supergiants, yellow hypergiants, luminous blue variables and Wolf-Rayet stars of the WN and WO subtypes. I finish by assessing the detectability of SN Ibc progenitors. This article is part of the themed issue 'Bridging the gap: from massive stars to supernovae'.

  1. Progenitor Cell Dysfunctions Underlie Some Diabetic Complications

    PubMed Central

    Rodrigues, Melanie; Wong, Victor W.; Rennert, Robert C.; Davis, Christopher R.; Longaker, Michael T.; Gurtner, Geoffrey C.

    2016-01-01

    Stem cells and progenitor cells are integral to tissue homeostasis and repair. They contribute to health through their ability to self-renew and commit to specialized effector cells. Recently, defects in a variety of progenitor cell populations have been described in both preclinical and human diabetes. These deficits affect multiple aspects of stem cell biology, including quiescence, renewal, and differentiation, as well as homing, cytokine production, and neovascularization, through mechanisms that are still unclear. More important, stem cell aberrations resulting from diabetes have direct implications on tissue function and seem to persist even after return to normoglycemia. Understanding how diabetes alters stem cell signaling and homeostasis is critical for understanding the complex pathophysiology of many diabetic complications. Moreover, the success of cell-based therapies will depend on a more comprehensive understanding of these deficiencies. This review has three goals: to analyze stem cell pathways dysregulated during diabetes, to highlight the effects of hyperglycemic memory on stem cells, and to define ways of using stem cell therapy to overcome diabetic complications. PMID:26079815

  2. Type Ia Supernovae: Colors, Rates, and Progenitors

    NASA Astrophysics Data System (ADS)

    Heringer, Epson; Pritchet, Chris; Kezwer, Jason; Graham, Melissa L.; Sand, David; Bildfell, Chris

    2017-01-01

    The rate of type Ia supernovae (SNe Ia) in a galaxy depends not only on stellar mass, but also on star formation history (SFH). Here we show that two simple observational quantities (g ‑ r or u ‑ r host galaxy color, and r-band luminosity), coupled with an assumed delay time distribution (DTD) (the rate of SNe Ia as a function of time for an instantaneous burst of star formation), are sufficient to accurately determine a galaxy’s SN Ia rate, with very little sensitivity to the precise details of the SFH. Using this result, we compare observed and predicted color distributions of SN Ia hosts for the MENeaCS cluster supernova survey, and for the SDSS Stripe 82 supernova survey. The observations are consistent with a continuous DTD, without any cutoff. For old progenitor systems, the power-law slope for the DTD is found to be -{1.50}-0.15+0.19. This result favors the double degenerate scenario for SN Ia, though other interpretations are possible. We find that the late-time slopes of the DTD are different at the 1σ level for low and high stretch supernova, which suggest a single degenerate (SD) scenario for the latter. However, due to ambiguity in the current models’ DTD predictions, SD progenitors can neither be confirmed as causing high stretch supernovae nor ruled out from contributing to the overall sample.

  3. 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.

  4. 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.

  5. Hierarchization of myogenic and adipogenic progenitors within human skeletal muscle.

    PubMed

    Pisani, Didier F; Clement, Noémie; Loubat, Agnès; Plaisant, Magali; Sacconi, Sabrina; Kurzenne, Jean-Yves; Desnuelle, Claude; Dani, Christian; Dechesne, Claude A

    2010-12-01

    Skeletal muscle cells constitute a heterogeneous population that maintains muscle integrity through a high myogenic regenerative capacity. More unexpectedly, this population is also endowed with an adipogenic potential, even in humans, and intramuscular adipocytes have been found to be present in several disorders. We tested the distribution of myogenic and adipogenic commitments in human muscle-derived cells to decipher the cellular basis of the myoadipogenic balance. Clonal analysis showed that adipogenic progenitors can be separated from myogenic progenitors and, interestingly, from myoadipogenic bipotent progenitors. These progenitors were isolated in the CD34(+) population on the basis of the expression of CD56 and CD15 cell surface markers. In vivo, these different cell types have been found in the interstitial compartment of human muscle. In vitro, we show that the proliferation of bipotent myoadipogenic CD56(+)CD15(+) progenitors gives rise to myogenic CD56(+)CD15(-) progenitors and adipogenic CD56(-)CD15(+) progenitors. A cellular hierarchy of muscle and fat progenitors thus occurs within human muscle. These results provide cellular bases for adipogenic differentiation in human skeletal muscle, which may explain the fat development encountered in different muscle pathological situations.

  6. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    PubMed Central

    Gehling, Ursula M; Willems, Marc; Schlagner, Kathleen; Benndorf, Ralf A; Dandri, Maura; Petersen, Jörg; Sterneck, Martina; Pollok, Joerg-Matthias; Hossfeld, Dieter K; Rogiers, Xavier

    2010-01-01

    AIM: To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS: Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay. RESULTS: Progenitor cells with a CD133+/CD45+/CD14+ phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit+ progenitor cells (between 1% and 38 % of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133+ progenitor cells. CONCLUSION: These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells. PMID:20066741

  7. 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

    2016-08-08

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Progenitor cells in arteriosclerosis: good or bad guys?

    PubMed

    Campagnolo, Paola; Wong, Mei Mei; Xu, Qingbo

    2011-08-15

    Accumulating evidence indicates that the mobilization and recruitment of circulating or tissue-resident progenitor cells that give rise to endothelial cells (ECs) and smooth muscle cells (SMCs) can participate in atherosclerosis, neointima hyperplasia after arterial injury, and transplant arteriosclerosis. It is believed that endothelial progenitor cells do exist and can repair and rejuvenate the arteries under physiologic conditions; however, they may also contribute to lesion formation by influencing plaque stability in advanced atherosclerotic plaque under specific pathologic conditions. At the same time, smooth muscle progenitors, despite their capacity to expedite lesion formation during restenosis, may serve to promote atherosclerotic plaque stabilization by producing extracellular matrix proteins. This profound evidence provides support to the hypothesis that both endothelial and smooth muscle progenitors may act as a double-edged sword in the pathogenesis of arteriosclerosis. Therefore, the understanding of the regulatory networks that control endothelial and smooth muscle progenitor differentiation is undoubtedly fundamental both for basic research and for improving current therapeutic avenues for atherosclerosis. We update the progress in progenitor cell study related to the development of arteriosclerosis, focusing specifically on the role of progenitor cells in lesion formation and discuss the controversial issues that regard the origins, frequency, and impact of the progenitors in the disease.

  9. GSK-3 is a master regulator of neural progenitor homeostasis

    PubMed Central

    Kim, Woo-Yang; Wang, Xinshuo; Wu, Yaohong; Doble, Bradley W; Patel, Satish; Woodgett, James R; Snider, William D

    2016-01-01

    The development of the brain requires the exquisite coordination of progenitor proliferation and differentiation to achieve complex circuit assembly. It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because of its essential role in the RTK, Wnt and Shh signaling pathways. We created conditional mutations that deleted both the α and β forms of GSK-3 in mouse neural progenitors. GSK-3 deletion resulted in massive hyperproliferation of neural progenitors along the entire neuraxis. Generation of both intermediate neural progenitors and postmitotic neurons was markedly suppressed. These effects were associated with the dysregulation of β-catenin, Sonic Hedgehog, Notch and fibroblast growth factor signaling. Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development. PMID:19801986

  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. Stem/Progenitor cells in vascular regeneration.

    PubMed

    Zhang, Li; Xu, Qingbo

    2014-06-01

    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

  13. The Progenitor of SN 1987A. [IUE

    NASA Technical Reports Server (NTRS)

    Sonneborn, G.

    1988-01-01

    Spatially resolved IUE spectra (1150 to 2000 A) taken at the position of SN 1987A in March 1987 show that the 12th mag B3 I star Sk -69 deg 202 disappeared. Only the fainter companion stars (Star 2 and Star 3) are present near the site of the supernova. It is concluded that Sk -69 deg 202 exploded to produce SN 1987A. The known characteristics of Sk -69 deg 202 are consistent with the interpretation that the progenitor was a relatively compact star, having a high-velocity low-density stellar wind prior to the outburst. Recent IUE spectra of SN 1987A (May 1988) show no evidence that Sk -69 deg 202 still exists inside the expanding ejecta.

  14. L1 Retrotransposition in Neural Progenitor Cells.

    PubMed

    Muotri, Alysson R

    2016-01-01

    Long interspersed nucleotide element 1 (LINE-1 or L1) is a family of non-LTR retrotransposons that can replicate and reintegrate into the host genome. L1s have considerably influenced mammalian genome evolution by retrotransposing during germ cell development or early embryogenesis, leading to massive genome expansion. For many years, L1 retrotransposons were viewed as a selfish DNA parasite that had no contribution in somatic cells. Historically, L1s were thought to only retrotranspose during gametogenesis and in neoplastic processes, but recent studies have shown that L1s are extremely active in the mouse, rat, and human neuronal progenitor cells (NPCs). These de novo L1 insertions can impact neuronal transcriptional expression, creating unique transcriptomes of individual neurons, possibly contributing to the uniqueness of the individual cognition and mental disorders in humans.

  15. 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.

  16. Identification of functional progenitor cells in the pulmonary vasculature

    PubMed Central

    Firth, Amy L.; Yuan, Jason X. -J.

    2012-01-01

    The pulmonary vasculature comprises a complex network of branching arteries and veins all functioning to reoxygenate the blood for circulation around the body. The cell types of the pulmonary artery are able to respond to changes in oxygen tension in order to match ventilation to perfusion. Stem and progenitor cells in the pulmonary vasculature are also involved, be it in angiogenesis, endothelial dysfunction or formation of vascular lesions. Stem and progenitor cells may be circulating around the body, residing in the pulmonary artery wall or stimulated for release from a central niche like the bone marrow and home to the pulmonary vasculature along a chemotactic gradient. There may currently be some controversy over the pathogenic versus therapeutic roles of stem and progenitor cells and, indeed, it is likely both chains of evidence are correct due to the specific influence of the immediate environmental niche a progenitor cell may be in. Due to their great plasticity and a lack of specific markers for stem and progenitor cells, they can be difficult to precisely identify. This review discusses the methodological approaches used to validate the presence of and subtype of progenitors cells in the pulmonary vasculature while putting it in context of the current knowledge of the therapeutic and pathogenic roles for such progenitor cells. PMID:22558524

  17. Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation

    PubMed Central

    2012-01-01

    Background Pannexin 1 forms ion and metabolite permeable hexameric channels and is abundantly expressed in the brain. After discovering pannexin 1 expression in postnatal neural stem and progenitor cells we sought to elucidate its functional role in neuronal development. Results We detected pannexin 1 in neural stem and progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP). Conclusions Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease. PMID:22458943

  18. Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors.

    PubMed

    Hendry, Caroline E; Vanslambrouck, Jessica M; Ineson, Jessica; Suhaimi, Norseha; Takasato, Minoru; Rae, Fiona; Little, Melissa H

    2013-09-01

    Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population of the embryonic kidney gives rise to all cells within the nephron other than the collecting duct through a mesenchyme-to-epithelial transition, but this population is exhausted around the time of birth. Here, we sought to identify the conditions under which adult proximal tubule cells could be directly transcriptionally reprogrammed to nephron progenitors. Using a combinatorial screen for lineage-instructive transcription factors, we identified a pool of six genes (SIX1, SIX2, OSR1, EYA1, HOXA11, and SNAI2) that activated a network of genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule (HK2) cell line. Consistent with these reprogrammed cells being nephron progenitors, we observed differential contribution of the reprogrammed population into the Six2(+) nephron progenitor fields of an embryonic kidney explant. Dereplication of the pool suggested that SNAI2 can suppress E-CADHERIN, presumably assisting in the epithelial-to-mesenchymal transition (EMT) required to form nephron progenitors. However, neither TGFβ-induced EMT nor SNAI2 overexpression alone was sufficient to create this phenotype, suggesting that additional factors are required. In conclusion, these results suggest that reinitiation of kidney development from a population of adult cells by generating embryonic progenitors may be feasible, opening the way for additional cellular and bioengineering approaches to renal repair and regeneration.

  19. Thrombopoietin is a growth factor for rat hepatic progenitors.

    PubMed

    Schmelzer, Eva; Deiwick, Andrea; Bruns, Helge; Fiegel, Henning C; Bader, Augustinus

    2008-03-01

    The liver is the primary site of hematopoiesis during fetal development; it has been shown that thrombopoietin (TPO) produced by the liver during fetal development is a major regulator of megakaryocytopoiesis. As maximum liver growth and hematopoiesis occur simultaneously, we hypothesized that TPO may act as a growth factor for hepatic progenitors. Therefore, the influence of TPO on the proliferation of fetal hepatic progenitors in vitro compared with that of adult hepatocytes was analyzed. The expression of the TPO receptor, c-mpl, was investigated in fetal and adult liver. Cell proliferation was measured by bromodeoxyuridine incorporation and total cell counts. TPO and c-mpl gene expression was investigated by reverse transcription polymerase chain reaction. The cell surface expression of c-mpl was analyzed in fetal and adult human liver by immunohistochemistry. Hepatic progenitors of fetal and adult liver but not hepatocytes expressed the TPO receptor, c-mpl, on the cell surface. Fetal hepatic progenitors expressed mRNA for TPO and its receptor. TPO stimulated cell proliferation and increased cell numbers of cultured rat fetal hepatic progenitors but not adult hepatocytes. We conclude that TPO acts in addition to its known role in megakaryocytopoiesis as a growth factor for hepatic progenitors but not hepatocytes in vitro; thus, TPO represents a growth factor for hepatic progenitors during fetal liver development.

  20. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    SciTech Connect

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Nomoto, Ken’ichi

    2015-10-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M{sub ⊙} and the radius was 30–50 R{sub ⊙}, which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion.

  1. Karyotype and cytogenetic mapping of 9 classes of repetitive DNAs in the genome of the naked catfish Mystus bocourti (Siluriformes, Bagridae)

    PubMed Central

    2013-01-01

    Background In the present study, conventional and molecular cytogenetic studies were performed in the naked catfish Mystus bocourti (Siluriformes, Bagridae). Besides the conventional Giemsa staining, fluorescence in situ hybridization (FISH) using nine classes of repetitive DNAs namely 5S and 18S rDNAs, U2 snRNA, the microsatellites (CA)15 and (GA)15, telomeric repeats, and the retrotransposable elements Rex1, 3 and 6. was also performed. Results M. bocourti had 2n = 56 chromosomes with a karyotype composed by 11 m + 11 sm + 6 st/a and a fundamental number (NF) equal to 100 in both sexes. Heteromorphic sex chromosome cannot be identified. The U2 snRNA, 5S and 18S rDNA were present in only one pair of chromosomes but none of them in a syntenic position. Microsatellites (CA)15 and (GA)15 showed hybridization signals at subtelomeric regions of all chromosomes with a stronger accumulation into one specific chromosomal pair. FISH with the telomeric probe revealed hybridization signals on each telomere of all chromosomes and interstitial telomeric sites (ITS) were not detected. The retrotransposable elements Rex1, 3 and 6 were generally spread throughout the genome. Conclusions In general, the repetitive sequences were not randomly distributed in the genome, suggesting a pattern of compartmentalization on the heterochromatic region of the chromosomes. Little is known about the structure and organization of bagrid genomes and the knowledge of the chromosomal distribution of repetitive DNA sequences in M. bocourti represents the first step for achieving an integrated view of their genomes. PMID:24266901

  2. A new genus and species of marine catfishes (Siluriformes; Ariidae) from the upper Eocene Birket Qarun Formation, Wadi El-Hitan, Egypt.

    PubMed

    El-Sayed, Sanaa E; Kora, Mahmoud A; Sallam, Hesham M; Claeson, Kerin M; Seiffert, Erik R; Antar, Mohammed S

    2017-01-01

    Wadi El-Hitan, the UNESCO World Heritage Site, of the Fayum Depression in the northeast part of the Western Desert of Egypt, has produced a remarkable collection of Eocene vertebrates, in particular the fossil whales from which it derives its name. Here we describe a new genus and species of marine catfishes (Siluriformes; Ariidae), Qarmoutus hitanensis, from the base of the upper Eocene Birket Qarun Formation, based on a partial neurocranium including the complete left side, partial right dentary, left suspensorium, two opercles, left pectoral girdle and spine, nuchal plates, first and second dorsal spines, Weberian apparatus and a disassociated series of abdominal vertebrae. All of the elements belong to the same individual and some of them were found articulated. Qarmoutus gen. nov. is the oldest and the most complete of the Paleogene marine catfishes unearthed from the Birket Qarun Formation. The new genus exhibits distinctive features not seen in other African Paleogene taxa, such as different sculpturing on the opercle and pectoral girdle with respect to that on the neurocranium and nuchal plates, denticulate ornamentation on the skull bones arranged in longitudinal rows and forming a radiating pattern on the sphenotic, pterotic, extrascapular and the parieto-supraoccipital, indentations or pitted ornamentation on the nuchal plates as well as the parieto-supraoccipital process, strut-like radiating pattern of ornamentation on the opercle from the proximal articulation to margins, longitudinal, curved, reticulate ridges and tubercular ornamentations on the cleithrum, sinuous articulation between the parieto-supraoccipital process and the anterior nuchal plate, long, narrow, and arrowhead shaped nuchal shield, very small otic capsules restricted to the prootic. Multiple parsimony and Bayesian morphological phylogenetic analyses of Ariidae, run with and without "molecular scaffolds", yield contradictory results for the placement of Qarmoutus; the genus is either

  3. A new genus and species of marine catfishes (Siluriformes; Ariidae) from the upper Eocene Birket Qarun Formation, Wadi El-Hitan, Egypt

    PubMed Central

    2017-01-01

    Wadi El-Hitan, the UNESCO World Heritage Site, of the Fayum Depression in the northeast part of the Western Desert of Egypt, has produced a remarkable collection of Eocene vertebrates, in particular the fossil whales from which it derives its name. Here we describe a new genus and species of marine catfishes (Siluriformes; Ariidae), Qarmoutus hitanensis, from the base of the upper Eocene Birket Qarun Formation, based on a partial neurocranium including the complete left side, partial right dentary, left suspensorium, two opercles, left pectoral girdle and spine, nuchal plates, first and second dorsal spines, Weberian apparatus and a disassociated series of abdominal vertebrae. All of the elements belong to the same individual and some of them were found articulated. Qarmoutus gen. nov. is the oldest and the most complete of the Paleogene marine catfishes unearthed from the Birket Qarun Formation. The new genus exhibits distinctive features not seen in other African Paleogene taxa, such as different sculpturing on the opercle and pectoral girdle with respect to that on the neurocranium and nuchal plates, denticulate ornamentation on the skull bones arranged in longitudinal rows and forming a radiating pattern on the sphenotic, pterotic, extrascapular and the parieto-supraoccipital, indentations or pitted ornamentation on the nuchal plates as well as the parieto-supraoccipital process, strut-like radiating pattern of ornamentation on the opercle from the proximal articulation to margins, longitudinal, curved, reticulate ridges and tubercular ornamentations on the cleithrum, sinuous articulation between the parieto-supraoccipital process and the anterior nuchal plate, long, narrow, and arrowhead shaped nuchal shield, very small otic capsules restricted to the prootic. Multiple parsimony and Bayesian morphological phylogenetic analyses of Ariidae, run with and without “molecular scaffolds”, yield contradictory results for the placement of Qarmoutus; the genus is

  4. In vitro toxicity of trichothecenes on human haematopoietic progenitors.

    PubMed

    Parent-Massin, D; Fuselier, R; Thouvenot, D

    1994-01-01

    The culture of human haematopoietic progenitors, Colony-Forming-Unit Granulocyte and Macrophage (CFU-GM), has been performed in the presence of four trichothecenes, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS), and deoxynivalenol (DON). Our results showed that trichothecenes were cytotoxic for human haematopoietic progenitors. This work and the analysis of results described in the literature allowed us to propose that the haematologic lesions observed during human intoxication could be due to a destruction of haematopoietic progenitors such as granulocytic and macrophage colony-forming cells.

  5. Vascular smooth muscle progenitor cells: building and repairing blood vessels.

    PubMed

    Majesky, Mark W; Dong, Xiu Rong; Regan, Jenna N; Hoglund, Virginia J

    2011-02-04

    Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.

  6. Effect of acyclovir and interferon on human hematopoietic progenitor cells.

    PubMed Central

    Parker, L M; Lipton, J M; Binder, N; Crawford, E L; Kudisch, M; Levin, M J

    1982-01-01

    Continuous in vitro exposure of human bone marrow cells to acyclovir (approximately 200 microM) or human leukocyte interferon (approximately 250 U/ml) caused 50% inhibition of granulocyte colony-forming cell differentiation. Colonies expressed in the presence of either agent were reduced both in size and number. Erythroid progenitors were more resistant than granulocyte progenitors to the antiproliferative effects of acyclovir. Progenitor cells of patients recovering from cytotoxic chemotherapy were no more sensitive to the effects of acyclovir or interferon than were cells obtained from patients before chemotherapy. PMID:6177284

  7. Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats

    PubMed Central

    Wang, Lin; Wang, Xiangdong; Xie, Guanhua; Wang, Lei; Hill, Colin K.; DeLeve, Laurie D.

    2012-01-01

    The ability of the liver to regenerate is crucial to protect liver function after injury and during chronic disease. Increases in hepatocyte growth factor (HGF) in liver sinusoidal endothelial cells (LSECs) are thought to drive liver regeneration. However, in contrast to endothelial progenitor cells, mature LSECs express little HGF. Therefore, we sought to establish in rats whether liver injury causes BM LSEC progenitor cells to engraft in the liver and provide increased levels of HGF and to examine the relative contribution of resident and BM LSEC progenitors. LSEC label-retaining cells and progenitors were identified in liver and LSEC progenitors in BM. BM LSEC progenitors did not contribute to normal LSEC turnover in the liver. However, after partial hepatectomy, BM LSEC progenitor proliferation and mobilization to the circulation doubled. In the liver, one-quarter of the LSECs were BM derived, and BM LSEC progenitors differentiated into fenestrated LSECs. When irradiated rats underwent partial hepatectomy, liver regeneration was compromised, but infusion of LSEC progenitors rescued the defect. Further analysis revealed that BM LSEC progenitors expressed substantially more HGF and were more proliferative than resident LSEC progenitors after partial hepatectomy. Resident LSEC progenitors within their niche may play a smaller role in recovery from partial hepatectomy than BM LSEC progenitors, but, when infused after injury, these progenitors engrafted and expanded markedly over a 2-month period. In conclusion, LSEC progenitor cells are present in liver and BM, and recruitment of BM LSEC progenitors is necessary for normal liver regeneration. PMID:22406533

  8. Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation.

    PubMed

    Garriock, Robert J; Chalamalasetty, Ravindra B; Kennedy, Mark W; Canizales, Lauren C; Lewandoski, Mark; Yamaguchi, Terry P

    2015-05-01

    In the development of the vertebrate body plan, Wnt3a is thought to promote the formation of paraxial mesodermal progenitors (PMPs) of the trunk region while suppressing neural specification. Recent lineage-tracing experiments have demonstrated that these trunk neural progenitors and PMPs derive from a common multipotent progenitor called the neuromesodermal progenitor (NMP). NMPs are known to reside in the anterior primitive streak (PS) region; however, the extent to which NMPs populate the PS and contribute to the vertebrate body plan, and the precise role that Wnt3a plays in regulating NMP self-renewal and differentiation are unclear. To address this, we used cell-specific markers (Sox2 and T) and tamoxifen-induced Cre recombinase-based lineage tracing to locate putative NMPs in vivo. We provide functional evidence for NMP location primarily in the epithelial PS, and to a lesser degree in the ingressed PS. Lineage-tracing studies in Wnt3a/β-catenin signaling pathway mutants provide genetic evidence that trunk progenitors normally fated to enter the mesodermal germ layer can be redirected towards the neural lineage. These data, combined with previous PS lineage-tracing studies, support a model that epithelial anterior PS cells are Sox2(+)T(+) multipotent NMPs and form the bulk of neural progenitors and PMPs of the posterior trunk region. Finally, we find that Wnt3a/β-catenin signaling directs trunk progenitors towards PMP fates; however, our data also suggest that Wnt3a positively supports a progenitor state for both mesodermal and neural progenitors. © 2015. Published by The Company of Biologists Ltd.

  9. 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

  10. Luminal progenitors restrict their lineage potential during mammary gland development.

    PubMed

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  11. Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

    PubMed Central

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-01-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. PMID:25688859

  12. Sox9 and programming of liver and pancreatic progenitors

    PubMed Central

    Kawaguchi, Yoshiya

    2013-01-01

    Recent advances in developmental biology have greatly expanded our understanding of progenitor cell programming and the fundamental roles that Sox9 plays in liver and pancreas organogenesis. In the last 2 years, several studies have dissected the behavior of the Sox9+ duct cells in adult organs, but conflicting results have left unanswered the long-standing question of whether physiologically functioning progenitors exist in adult liver and pancreas. On the other hand, increasing evidence suggests that duct cells function as progenitors in the tissue restoration process after injury, during which embryonic programs are sometimes reactivated. This article discusses the role of Sox9 in programming liver and pancreatic progenitors as well as controversies in the field. PMID:23635786

  13. Circulating endothelial progenitor cells in periodontitis.

    PubMed

    Jönsson, Daniel; Spinell, Thomas; Vrettos, Anastasios; Stoecklin-Wasmer, Christin; Celenti, Romanita; Demmer, Ryan T; Kebschull, Moritz; Papapanou, Panos N

    2014-12-01

    Several biologically plausible mechanisms have been proposed to mediate the association between periodontitis and atherosclerotic vascular disease (AVD), including adverse effects on vascular endothelial function. Circulating endothelial progenitor cells (cEPCs) are known to contribute to vascular repair, but limited data are available regarding the relationship between cEPC levels and periodontitis. The aims of this cross-sectional study are to investigate the levels of hemangioblastic and monocytic cEPCs in patients with periodontitis and periodontally healthy controls and to associate cEPC levels with the extent and severity of periodontitis. A total of 112 individuals (56 patients with periodontitis and 56 periodontally healthy controls, aged 26 to 65 years; mean age: 43 years) were enrolled. All participants underwent a full-mouth periodontal examination and provided a blood sample. Hemangioblastic cEPCs were assessed using flow cytometry, and monocytic cEPCs were identified using immunohistochemistry in cultured peripheral blood mononuclear cells. cEPC levels were analyzed in the entire sample, as well as in a subset of 50 pairs of patients with periodontitis/periodontally healthy controls, matched with respect to age, sex, and menstrual cycle. Levels of hemangioblastic cEPCs were approximately 2.3-fold higher in patients with periodontitis than periodontally healthy controls, after adjustments for age, sex, physical activity, systolic blood pressure, and body mass index (P = 0.001). A non-significant trend for higher levels of monocytic cEPCs in periodontitis was also observed. The levels of hemangioblastic cEPCs were positively associated with the extent of bleeding on probing, probing depth, and clinical attachment loss. Hemangioblastic and monocytic cEPC levels were not correlated (Spearman correlation coefficient 0.03, P = 0.77), suggesting that they represent independent populations of progenitor cells. These findings further support the notion that

  14. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    PubMed Central

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  15. The Limbal Epithelial Progenitors in the Limbal Niche Environment

    PubMed Central

    Zhang, Yuan; Sun, Hong; Liu, Yongsong; Chen, Shuangling; Cai, Subo; Zhu, Yingting; Guo, Ping

    2016-01-01

    Limbal epithelial progenitors are stem cells located in limbal palisades of vogt. In this review, we present the audience with recent evidence that limbal epithelial progenitors may be a powerful stem cell resource for the cure of human corneal stem cell deficiency. Further understanding of their mechanism may shed lights to the future successful application of stem cell therapy not only to the eye tissue, but also to the other tissues in the human body. PMID:27877075

  16. Dendritic cell potentials of early lymphoid and myeloid progenitors.

    PubMed

    Manz, M G; Traver, D; Miyamoto, T; Weissman, I L; Akashi, K

    2001-06-01

    It has been proposed that there are at least 2 classes of dendritic cells (DCs), CD8alpha(+) DCs derived from the lymphoid lineage and CD8alpha(-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their overall contributions to the DC compartment are evaluated. It has previously been shown that primitive myeloid-committed progenitors (common myeloid progenitors [CMPs]) are efficient precursors of both CD8alpha(+) and CD8alpha(-) DCs in vivo. Here it is shown that the earliest lymphoid-committed progenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny granulocyte-macrophage progenitors (GMPs) can give rise to functional DCs in vitro and in vivo. CLPs are more efficient in generating DCs than their T-lineage descendants, the early thymocyte progenitors and pro-T cells, and CMPs are more efficient DC precursors than the descendant GMPs, whereas pro-B cells and megakaryocyte-erythrocyte progenitors are incapable of generating DCs. Thus, DC developmental potential is preserved during T- but not B-lymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP. In vivo reconstitution experiments show that CLPs and CMPs can reconstitute CD8alpha(+) and CD8alpha(-) DCs with similar efficiency on a per cell basis. However, CMPs are 10-fold more numerous than CLPs, suggesting that at steady state, CLPs provide only a minority of splenic DCs and approximately half the DCs in thymus, whereas most DCs, including CD8alpha(+) and CD8alpha(-) subtypes, are of myeloid origin. (Blood. 2001;97:3333-3341)

  17. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.

    PubMed

    Doyle, Margaret F; Tracy, Russell P; Parikh, Megha A; Hoffman, Eric A; Shimbo, Daichi; Austin, John H M; Smith, Benjamin M; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.

  18. Characterization of Botulinum Progenitor Toxins by Mass Spectrometry†

    PubMed Central

    Hines, Harry B.; Lebeda, Frank; Hale, Martha; Brueggemann, Ernst E.

    2005-01-01

    Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases. All proteins known to be present in progenitor toxins from each serotype were identified. Additional proteins, including flagellins, ORF-X1, and neurotoxin binding protein, not previously reported to be associated with progenitor toxins, were present also in samples from several serotypes. Protein identification was used to assign toxins to a serotype and strain. Serotype assignments were accurate, and strain assignments were best when either sufficient nucleotide or amino acid sequence data were available. Minor difficulties were encountered using neurotoxin-associated protein identification for assigning serotype and strain. This study found that combined nanoscale chromatographic and mass spectrometric techniques can characterize C. botulinum progenitor toxin protein composition and that serotype/strain assignments based upon these proteins can provide accurate serotype and, in most instances, strain assignments using currently available information. Assignment accuracy will continue to improve as more nucleotide/amino acid sequence information becomes available for different botulinum strains. PMID:16085839

  19. Characterization of botulinum progenitor toxins by mass spectrometry.

    PubMed

    Hines, Harry B; Lebeda, Frank; Hale, Martha; Brueggemann, Ernst E

    2005-08-01

    Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases. All proteins known to be present in progenitor toxins from each serotype were identified. Additional proteins, including flagellins, ORF-X1, and neurotoxin binding protein, not previously reported to be associated with progenitor toxins, were present also in samples from several serotypes. Protein identification was used to assign toxins to a serotype and strain. Serotype assignments were accurate, and strain assignments were best when either sufficient nucleotide or amino acid sequence data were available. Minor difficulties were encountered using neurotoxin-associated protein identification for assigning serotype and strain. This study found that combined nanoscale chromatographic and mass spectrometric techniques can characterize C. botulinum progenitor toxin protein composition and that serotype/strain assignments based upon these proteins can provide accurate serotype and, in most instances, strain assignments using currently available information. Assignment accuracy will continue to improve as more nucleotide/amino acid sequence information becomes available for different botulinum strains.

  20. Biology and Flow Cytometry of Proangiogenic Hematopoietic Progenitors Cells

    PubMed Central

    Rose, Jonathan A.; Erzurum, Serpil; Asosingh, Kewal

    2015-01-01

    During development hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative “endothelial progenitor cells” that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multi-disciplinary expertise in flow cytometry, hematology and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and bone marrow. PMID:25418030

  1. Dual Function of Sox1 in Telencephalic Progenitor Cells

    PubMed Central

    Kan, Lixin; Jalali, Ali; Zhao, Li-Ru; Zhou, Xiaojing; McGuire, Tammy; Kazanis, Ilias; Episkopou, Vasso; Bassuk, Alexander G.; Kessler, John A.

    2012-01-01

    The transcription factor, Sox1 has been implicated in the maintenance of neural progenitor cell status, but accumulating evidence suggests that this is only part of its function. This study examined the role of Sox1 expression in proliferation, lineage commitment, and differentiation by telencephalic neural progenitor cells in vitro and in vivo, and further clarified the pattern of Sox1 expression in postnatal and adult mouse brain. Telencephalic neural progenitor cells isolated from Sox1 null embryos formed neurospheres normally, but were specifically deficient in neuronal differentiation. Conversely, overexpression of Sox1 in the embryonic telencephalon in vivo both expanded the progenitor pool and biased neural progenitor cells towards neuronal lineage commitment. Sox1 mRNA and protein were found to be persistently expressed in the postnatal and adult brain in both differentiated and neurogenic regions. Importantly, in differentiated regions Sox1 co-labeled only with neuronal markers. These observations, coupled with previous studies, suggest that Sox1 expression by early embryonic progenitor cells initially helps to maintain the cells in cell cycle, but that continued expression subsequently promotes neuronal lineage commitment. PMID:17719572

  2. Interstitial stromal progenitors during kidney development: here, there and everywhere.

    PubMed

    Fanni, Daniela; Gerosa, Clara; Vinci, Laura; Ambu, Rossano; Dessì, Angelica; Eyken, Peter Van; Fanos, Vassilios; Faa, Gavino

    2016-12-01

    In recent years, the renal interstitium has been identified as the site of multiple cell types, giving rise to multiple contiguous cellular networks with multiple fundamental structural and functional roles. Few studies have been carried out on the morphological and functional properties of the stromal/interstitial renal cells during the intrauterine life. This work was aimed at reviewing the peculiar features of renal interstitial stem/progenitor cells involved in kidney development. The origin of the renal interstitial progenitor cells remains unknown. During kidney development, besides the Six2 + cells of the cap mesenchyme, a self-renewing progenitor population, characterized by the expression of Foxd1, represents the first actor of the non-nephrogenic lineage. Foxd1 + interstitial progenitors originate the cortical and the renal medullary interstitial progenitors. Here, the most important stromal/interstitial compartments present in the developing human kidney will be analyzed: capsular stromal cells, cortical interstitial cells, medullary interstitial cells, the interstitium inside the renal stem cell niche, Hilar interstitial cells and Ureteric interstitial cells. Data reported here indicate that the different interstitial compartments of the developing kidney are formed by different cell types that characterize the different renal areas. Further studies are needed to better characterize the different pools of renal interstitial progenitors and their role in human nephrogenesis.

  3. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    PubMed

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  4. 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

  5. Harnessing endogenous stem/progenitor cells for tendon regeneration.

    PubMed

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

    2015-07-01

    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.

  6. Constraining the Progenitor Masses of Core Collapse Supernova Remnants

    NASA Astrophysics Data System (ADS)

    Díaz Rodríguez, Mariangelly; Murphy, Jeremiah Wayne; Elwood, Benjamin; Williams, Benjamin F.; Rubin, David

    2016-01-01

    Understanding the progenitor mass distribution of supernova explosions is an important observational constraint of stellar evolution theory. Recently, a novel approach was proposed to significantly increase the number of progenitor masses: characterize the progenitor mass of supernova remnants (SNRs) by age-dating the local stellar population. Preliminary statistical analyses suggested that there is a lack of SNRs around the most massive of massive stars. This suggested that there is a maximum mass for core collapse supernova explosions, or there is a bias against finding SNRs associated with the most massive stars. We test for a bias by considering the distribution of SNRs sizes using a Monte Carlo simulation. We find that the distribution of remnants sizes is the same for low mass progenitors and high mass progenitors. This implies that there is no bias against finding SNRs around the most massive progenitors. Our next step is to apply Bayesian statistical inference and obtain the joint probability for all the parameters involved in the statistical distribution model: the minimum mass, maximum mass, and slope of the mass distribution.

  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.

  8. [Characterization of hematopoietic progenitor cells during the human embryonic development].

    PubMed

    Coulombel, L; Huyhn, A; Izac, B

    1995-01-01

    In a search for assays that might facilitate identification of pluripotent stem cells with extended potentialities, we analysed the properties of hematopoietic progenitor cells detected in the extraembryonic yolk sac and in the intraembryonic part of human embryos between approximately 28 and 45 days of development. Cells from the yolk sac, the liver rudiment and the remainder of the embryo were plated in semi solid methylcellulose colony-assays supplemented with combinations of cytokines. Large BFU-E-derived colonies as well as granulocytic colonies were detected in every yolk sac sample. Interestingly, progenitor cells were also detected in the intraembryonic part, outside the liver and a subclass of these progenitors were detected that generated large granulomacrophagic colonies capable of generating secondary colonies when replated. These were preferentially located in the embryo. Colony-assays initiated with CD34+ cells sorted from the different tissues confirmed these data. These results first indicate that embryonic progenitors exhibit unique phenotypic features, and second, analysis of the distribution of progenitors between the different tissues may suggest the existence of other sites of hematopoietic production. More detailed analysis of the potentialities of these progenitors should now be assessed in vitro in cocultures assays and in vivo by reconstituting immunodeficient mice.

  9. On the progenitor of the Type IIb supernova 2016gkg

    NASA Astrophysics Data System (ADS)

    Kilpatrick, Charles D.; Foley, Ryan J.; Abramson, Louis E.; Pan, Yen-Chen; Lu, Cicero-Xinyu; Williams, Peter; Treu, Tommaso; Siebert, Matthew R.; Fassnacht, Christopher D.; Max, Claire E.

    2017-03-01

    We present a detection in pre-explosion Hubble Space Telescope (HST) imaging of a point source consistent with being the progenitor star of the Type IIb supernova (SN IIb) 2016gkg. Post-explosion imaging from the Keck adaptive optics system was used to perform relative astrometry between the Keck and HST imaging. We identify a single point source in the HST images coincident with the SN position to 0.89σ. The HST photometry is consistent with the progenitor star being an A0 Ia star with T = 9500 K and log (L/L⊙) = 5.15. We find that the SN 2016gkg progenitor star appears more consistent with binary than single-star evolutionary models. In addition, early-time light-curve data from SN 2016gkg revealed a rapid rise in luminosity within ∼0.4 d of non-detection limits, consistent with models of the cooling phase after shock break-out. We use these data to determine an explosion date of 2016 September 20.15 and progenitor-star radius of log (R/R⊙) = 2.41, which agrees with photometry from the progenitor star. Our findings are also consistent with detections of other SNe IIb progenitor stars, although more luminous and bluer than most other examples.

  10. 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.

  11. Large volume leukapheresis maximizes the progenitor cell yield for allogeneic peripheral blood progenitor donation.

    PubMed

    Kobbe, G; Soehngen, D; Heyll, A; Fischer, J; Thiele, K P; Aul, C; Wernet, P

    1997-04-01

    We have investigated the efficiency and safety of large volume leukapheresis (LVL) for the collection of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) from healthy donors. In six apheresis sessions in four healthy individuals on a COBE-BCT Spectra cell separator (median processed volume 3.5 X total blood volume, TBV, range 3.3-4.4 X TBV), harvested cells were collected sequentially into three single bags. The collection bags were changed after processing 33%, 66%, and 100% of the prospective apheresis volume, allowing analysis of PBPCs collected at different periods during one harvest. Mononuclear cells (MNCs), CD34+ cells, CD34+ subsets, and lymphocyte subsets were determined in each bag. Substantially more PBPCs were harvested than were in the circulation before G-CSF administration preceding LVL (median 171%, range 69-267%), reflecting progenitor release during the procedure. In donors 1 and 3, the CD34+ cell yields decreased in the third bag to 53% and 42% of that collected in the first bag, whereas the progenitor cell yields in donors 2 and 4 were stable or rose during the procedure, achieving in the third bag 157% and 105% of the number of CD34+ cells collected in the first bag. Minor changes were found in the subsets of CD34+ cells, lymphocytes, and monocytes collected at different periods during a single harvest. LVL was well tolerated. Reversible thombocytopenia developed in all cases. No late effects attributable to LVL or G-CSF were found in the 4 donors and 16 other healthy individuals who have undergone LVL in our institution. We conclude that LVL is safe and maximizes PBPC yields for allogeneic transplantation.

  12. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells

    PubMed Central

    1985-01-01

    Data from previous multiparameter fluorescence-activated cell sorter (FACS) analysis and sorting studies define a subset of murine B cells that expresses the Ly-1 surface determinant in conjunction with IgM, IgD, Ia, and other typical B cell markers. These Ly-1 B cells are physically and functionally distinct. They express more IgM and less IgD than most other B cells; they are not normally found in lymph node or bone marrow; they are always present at low frequencies (1-5%) in normal spleens, and, as we show here, they comprise about half of the B cells (10-20% of total cells) recovered from the peritoneal cavity in normal mice. Furthermore, most of the commonly studied IgM autoantibodies in normal and autoimmune mice are produced by these Ly-1 B cells, even though they seldom produce antibodies to exogenous antigens such as trinitrophenyl-Ficoll or trinitrophenyl-keyhole limpet hemocyanin. Cell transfer studies presented here demonstrate that the progenitors of Ly-1 B cells are different from the progenitors of the predominant B cell populations in spleen and lymph node. In these studies, we used FACS analysis and functional assays to characterize donor-derived (allotype-marked) B cells present in lethally irradiated recipients 1-2 mo after transfer. Surprisingly, adult bone marrow cells typically used to reconstitute B cells in irradiated recipients selectively failed to reconstitute the Ly-1 B subset. Liver, spleen, and bone marrow cells from young mice, in contrast, reconstituted all B cells (including Ly-1 B), and peritoneal "washout" cells (PerC) from adult mice uniquely reconstituted Ly-1 B. Bone marrow did not block Ly- 1 B development, since PerC and newborn liver still gave rise to Ly-1 B when jointly transferred with marrow. These findings tentatively assign Ly-1 B to a distinct developmental lineage originating from progenitors that inhabit the same locations as other B cell progenitors in young animals, but move to unique location(s) in adults. PMID

  13. 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.

  14. 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

  15. Role of liver progenitors in liver regeneration.

    PubMed

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

    2015-02-01

    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.

  16. Human Retinal Progenitor Cell Transplantation Preserves Vision*

    PubMed Central

    Luo, Jing; Baranov, Petr; Patel, Sherrina; Ouyang, Hong; Quach, John; Wu, Frances; Qiu, Austin; Luo, Hongrong; Hicks, Caroline; Zeng, Jing; Zhu, Jing; Lu, Jessica; Sfeir, Nicole; Wen, Cindy; Zhang, Meixia; Reade, Victoria; Patel, Sara; Sinden, John; Sun, Xiaodong; Shaw, Peter; Young, Michael; Zhang, Kang

    2014-01-01

    Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment. PMID:24407289

  17. Developmental origin of postnatal cardiomyogenic progenitor cells

    PubMed Central

    Liu, Yuan-Hung; Lai, Ling-Ping; Huang, Shih-Yun; Lin, Yi-Shuan; Wu, Shinn-Chih; Chou, Chih-Jen; Lin, Jiunn-Lee

    2016-01-01

    Aim: To trace the cell origin of the cells involved in postnatal cardiomyogenesis. Materials & methods: Nkx2.5 enhancer-eGFP (Nkx2.5 enh-eGFP) mice were used to test the cardiomyogenic potential of Nkx2.5 enhancer-expressing cells. By analyzing Cre excision of activated Nkx2.5-eGFP+ cells from different lineage-Cre/Nkx2.5 enh-eGFP/ROSA26 reporter mice, we traced the developmental origin of Nkx2.5 enhancer-expressing cells. Results: Nkx2.5 enhancer-expressing cells could differentiate into striated cardiomyocytes both in vitro and in vivo. Nkx2.5-eGFP+ cells increased remarkably after experimental myocardial infarction (MI). The post-MI Nkx2.5-eGFP+ cells originated from the embryonic epicardial cells, not from the pre-existing cardiomyocytes, endothelial cells, cardiac neural crest cells or perinatal/postnatal epicardial cells. Conclusion: Postnatal Nkx2.5 enhancer-expressing cells are cardiomyogenic progenitor cells and originate from embryonic epicardium-derived cells. PMID:28031967

  18. NFAT restricts osteochondroma formation from entheseal progenitors

    PubMed Central

    Tsang, Kelly; He, Lizhi; Garcia, Roberto A.; Ermann, Joerg; Mizoguchi, Fumitaka; Zhang, Minjie; 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

  19. Harmine stimulates proliferation of human neural progenitors

    PubMed Central

    Dakic, Vanja; Maciel, Renata de Moraes; Drummond, Hannah; Nascimento, Juliana M.; Trindade, Pablo

    2016-01-01

    Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo. PMID:27957390

  20. Two distinct muscle progenitor populations coexist throughout amniote development.

    PubMed

    Picard, Cyril A; Marcelle, Christophe

    2013-01-01

    During embryonic and fetal life, skeletal muscle growth is dependent upon the proliferation and the differentiation of a population of resident muscle progenitors, from which derive the muscle stem cells of the adult, the satellite cells. Under poorly defined extrinsic and intrinsic influences, muscle progenitors proliferate, differentiate or enter a quiescent state to become reserve satellite cells. Despite their primordial role, surprisingly little is known on the homeostasis of resident progenitors during embryogenesis. Preliminary studies in chick and mouse describing the key progenitor populations contributing to muscle growth during embryogenesis have led to differing results that could be due to technical issues or to fundamental differences between animal models. To address this question, we have undertaken a comprehensive analysis of the state of differentiation and proliferation of muscle progenitor cells from the time of their emergence within the dermomyotome until late fetal life, when they adopt a satellite cell-like position under the basal lamina. This was done by immunostaining against key players of myogenic differentiation, in muscles chosen from different regions of the body in two model organisms, the chick and mouse. This study identified two co-existing populations of progenitors during embryonic and fetal life in both chick and mouse: a minor, slow-cycling pool of undifferentiated resident progenitors which express Pax7, co-existing with a major fast-cycling population that co-express Pax7 and the early myogenic differentiation marker Myf5. We found that the overall proliferation rate of both progenitors drastically decreased with embryonic age, as an increasingly large portion of slow and fast-cycling progenitors entered quiescence during development. Together, this data suggests that the cellular strategies that drive muscle growth during embryonic and fetal life are remarkably conserved in amniotes throughout evolution. They rely on the

  1. 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

  2. The direct identification of core-collapse supernova progenitors

    NASA Astrophysics Data System (ADS)

    Van Dyk, Schuyler D.

    2017-09-01

    To place core-collapse supernovae (SNe) in context with the evolution of massive stars, it is necessary to determine their stellar origins. I describe the direct identification of SN progenitors in existing pre-explosion images, particularly those obtained through serendipitous imaging of nearby galaxies by the Hubble Space Telescope. I comment on specific cases representing the various core-collapse SN types. Establishing the astrometric coincidence of a SN with its putative progenitor is relatively straightforward. One merely needs a comparably high-resolution image of the SN itself and its stellar environment to perform this matching. The interpretation of these results, though, is far more complicated and fraught with larger uncertainties, including assumptions of the distance to and the extinction of the SN, as well as the metallicity of the SN environment. Furthermore, existing theoretical stellar evolutionary tracks exhibit significant variations one from the next. Nonetheless, it appears fairly certain that Type II-P (plateau) SNe arise from massive stars in the red supergiant phase. Many of the known cases are associated with subluminous Type II-P events. The progenitors of Type II-L (linear) SNe are less established. Among the stripped-envelope SNe, there are now a number of examples of cool, but not red, supergiants (presumably in binaries) as Type IIb progenitors. We appear now finally to have an identified progenitor of a Type Ib SN, but no known example yet for a Type Ic. The connection has been made between some Type IIn SNe and progenitor stars in a luminous blue variable phase, but that link is still thin, based on direct identifications. Finally, I also describe the need to revisit the SN site, long after the SN has faded, to confirm the progenitor identification through the star's disappearance and potentially to detect a putative binary companion that may have survived the explosion. This article is part of the themed issue 'Bridging the gap

  3. Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells.

    PubMed

    Vela, José M; Molina-Holgado, Eduardo; Arévalo-Martín, Angel; Almazán, Guillermina; Guaza, Carmen

    2002-07-01

    Interleukin-1 (IL-1) is a pleiotropic cytokine expressed during normal CNS development and in inflammatory demyelinating diseases, but remarkably little is known about its effect on oligodendroglial cells. In this study we explored the role of IL-1beta in oligodendrocyte progenitors and differentiated oligodendrocytes. The effects of IL-1beta were compared to those of IL-1 receptor antagonist, the specific inhibitor of IL-1 activity, since progenitors and differentiated oligodendrocytes produce IL-1beta and express IL-1 receptors. Unlike other proinflammatory cytokines (TNFalpha and IFNgamma), IL-1beta was not toxic for oligodendrocyte lineage cells. However, this cytokine inhibited proliferation of oligodendrocyte progenitors in the presence of growth factors (PDGF plus bFGF). This was evidenced by a significant decrease in both cells incorporating bromodeoxyuridine (45%) and total cell numbers (57%) after 6 days of treatment. Interestingly, IL-1beta blocked proliferation at the late progenitor/prooligodendrocyte (O4+) stage but did not affect proliferation of early progenitors (A2B5+). Inhibition of proliferation paralleled with promotion of differentiation, as revealed by the increased percentage of R-mab+ cells (6.7-fold). Moreover, when oligodendrocyte progenitors were allowed to differentiate in the absence of growth factors, treatment with IL-1beta promoted maturation to the MBP+ stage (4.2-fold) and survival of differentiating oligodendrocytes (2.1-fold). Regarding intracellular signaling, IL-1beta activated the p38 mitogen-activated protein kinase (MAPK) but not the p42/p44 MAPK and, when combined with growth factors, intensified p38 activation but inhibited the growth-factor-induced p42/p44 activation. IL-1beta also induced a time-dependent inhibition of PFGF-Ralpha gene expression. These results support a role for IL-1beta in promoting mitotic arrest and differentiation of oligodendrocyte progenitors as well as maturation and survival of differentiating

  4. Characterization of hematopoietic progenitors from human yolk sacs and embryos.

    PubMed

    Huyhn, A; Dommergues, M; Izac, B; Croisille, L; Katz, A; Vainchenker, W; Coulombel, L

    1995-12-15

    Hematopoiesis first arises in the extraembryonic yolk sac, and it is generally believed that yolk sac-derived stem cells migrate and seed the fetal liver at approximately week 6 of development in humans. Recently, the identification at day 8.5 to 9 of multipotential stem cells in intraembryonic sites different from the liver suggests that the establishment of hematopoiesis might be more complex than initially believed. In an attempt to understand initial steps of hematopoiesis during human ontogeny, we characterized clonogenic myeloid progenitor cells in human yolk sacs and corresponding embryos at 25 to 50 days of development. Most erythroid colonies derived from the yolk sacs differed from adult marrow-derived progenitors in that they also contained cells of the granulomacrophagic lineage, suggesting that they were pluripotent and exhibited a different response to cytokines. Furthermore, a subclass of nonerythroid progenitors generated very large granulomacrophagic colonies, some of which generated secondary erythroid colonies on replating. Analysis of the distribution of progenitors revealed that in contrast to erythroid progenitors, whose numbers were equally distributed between the yolk sac and the embryo, 80% of the nonerythroid progenitors were found in the embryo at stages II and III. Interestingly, a high proportion of nonerythroid progenitors (including high proliferative potential cells) was present in colony assays initiated with cells remaining after the liver has been removed. These findings were validated in colony assays established with CD34+ cells purified from extraembryonic yolk sacs and intraembryonic tissues. Increased knowledge about the biology of hematopoietic stem cells early in life may help to further understanding of the mechanisms associated with the restriction in proliferative and differentiative potential observed in the adult hematopoietic stem cell compartment.

  5. Epigenetic States of nephron progenitors and epithelial differentiation.

    PubMed

    Adli, Mazhar; Parlak, Mahmut; Li, Yuwen; El-Dahr, Samir S

    2015-06-01

    In mammals, formation of new nephrons ends perinatally due to consumption of mesenchymal progenitor cells. Premature depletion of progenitors due to prematurity or postnatal loss of nephrons due to injury causes chronic kidney disease and hypertension. Intensive efforts are currently invested in designing regenerative strategies to form new nephron progenitors from pluripotent cells, which upon further differentiation provide a potential source of new nephrons. To know if reprogramed renal cells can maintain their identity and fate requires knowledge of the epigenetic states of native nephron progenitors and their progeny. In this article, we summarize current knowledge and gaps in the epigenomic landscape of the developing kidney. We now know that Pax2/PTIP/H3K4 methyltransferase activity provides the initial epigenetic specification signal to the metanephric mesenchyme. During nephrogenesis, the cap mesenchyme housing nephron progenitors is enriched in bivalent chromatin marks; as tubulogenesis proceeds, the tubular epithelium acquires H3K79me2. The latter mark is uniquely induced during epithelial differentiation. Analysis of histone landscapes in clonal metanephric mesenchyme cell lines and in Wilms tumor and normal fetal kidney has revealed that promoters of poised nephrogenesis genes carry bivalent histone signatures in progenitors. Differentiation or stimulation of Wnt signaling promotes resolution of bivalency; this does not occur in Wilms tumor cells consistent with their developmental arrest. The use of small cell number ChIP-Seq should facilitate the characterization of the chromatin landscape of the metanephric mesenchyme and various nephron compartments during nephrogenesis. Only then we will know if stem and somatic cell reprogramming into kidney progenitors recapitulates normal development. © 2015 Wiley Periodicals, Inc.

  6. Quadriacanthus species (Monogenea: Dactylogyridae) from catfishes (Teleostei: Siluriformes) in eastern Africa: new species, new records and first insights into interspecific genetic relationships.

    PubMed

    Francová, Kateřina; Seifertová, Mária; Blažek, Radim; Gelnar, Milan; Mahmoud, Zuheir N; Řehulková, Eva

    2017-08-01

    African catfishes of the families Bagridae and Clariidae are known to be parasitized with monogeneans of Quadriacanthus Paperna, 1961 (Dactylogyridae). The genus remains taxonomically challenging due to its speciose nature and relatively wide host range representing two fish orders, i.e. Siluriformes and Osteoglossiformes, in Africa and Asia. Here, we investigated diversity of Quadriacanthus spp. parasitizing Clarias gariepinus (Burchell), Heterobranchus bidorsalis Geoffroy Saint-Hilaire, and Bagrus docmak (Forsskål) collected in the Lake Turkana (Kenya) and Nile River Basin (Sudan). The interspecific relationships among Quadriacanthus spp. parasitizing catfishes inferred from ribosomal DNA sequences were investigated for the first time. A combined morphological and molecular approach was used for description of the new species and for a critical review of the previously described Quadriacanthus spp., by means of phase contrast microscopic examination of sclerotized structures, and assessing the genetic divergence among the species found using rDNA sequences. Seven species (including four new) of Quadriacanthus were identified. These were as follows: Quadriacanthus aegypticus El-Naggar & Serag, 1986, Quadriacanthus clariadis Paperna, 1961, Quadriacanthus fornicatus n. sp., Quadriacanthus pravus n. sp., and Quadriacanthus zuheiri n. sp. from Clarias gariepinus (Clariidae); Quadriacanthus mandibulatus n. sp. from Heterobranchus bidorsalis (Clariidae); and Quadriacanthus bagrae Paperna, 1979 from Bagrus docmak (Bagridae). For both 18S-ITS1 and 28S rDNA regions, Q. clariadis from a clariid fish was found to be most closely related to Q. bagrae from a bagrid host. Quadriacanthus mandibulatus n. sp. was observed to be the most distant species from the others. The separation of Q. mandibulatus n. sp. from the other species corresponds with the different morphology of its copulatory tube. The copulatory tube is terminally enlarged in Q. mandibulatus n. sp., while the tube

  7. 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

  8. [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.

  9. Fas Activation Increases Neural progenitor Cell Survival

    PubMed Central

    Knight, Julia C.; Scharf, Eugene L.; Mao-Draayer, Yang

    2015-01-01

    Although there is a sizable amount of research focusing on adult neural progenitor cells (NPCs) as a therapeutic approach for many neurodegenerative diseases, including multiple sclerosis, little is known about the pathways that govern NPC survival and apoptosis. Fas, a member of the death receptor superfamily, plays a well-characterized role in the immune system, but its function in neural stem cells remains uncertain. Our study focuses on the effects of Fas on NPC survival in vitro. Activation of Fas by recombinant Fas ligand (FasL) did not induce apoptosis in murine NPCs in culture. In fact, both an increase in the amount of viable cells and a decrease in apoptotic and dying cells were observed with FasL treatment. Our data indicate that FasL-mediated adult NPC neuroprotection is characterized by a reduction in apoptosis, but not increased proliferation. Further investigation of this effect revealed that the antiapoptotic effects of FasL are mediated by the up-regulation of Birc3, an inhibitor of apoptosis protein (IAP). Conversely, the observed effect is not the result of altered caspase activation or FLIP (Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein) up-regulation, which is known to inhibit caspase-8-mediated cell death in T cells. Our data indicate that murine adult NPCs are resistant to FasL-induced cell death. Activation of Fas increased cell survival by decreasing apoptosis through Birc3 up-regulation. These results describe a novel pathway involved in NPC survival. PMID:19830835

  10. 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

  11. Myostatin promotes the terminal differentiation of embryonic muscle progenitors.

    PubMed

    Manceau, Marie; Gros, Jérôme; Savage, Kathleen; Thomé, Virginie; McPherron, Alexandra; Paterson, Bruce; Marcelle, Christophe

    2008-03-01

    Myostatin, a TGF-beta family member, is an important regulator of adult muscle size. While extensively studied in vitro, the mechanisms by which this molecule mediates its effect in vivo are poorly understood. We addressed this question using chick and mouse embryos. We show that while myostatin overexpression in chick leads to an exhaustion of the muscle progenitor population that ultimately results in muscle hypotrophy, myostatin loss of function in chick and mouse provokes an expansion of this population. Our data demonstrate that myostatin acts in vivo to regulate the balance between proliferation and differentiation of embryonic muscle progenitors by promoting their terminal differentiation through the activation of p21 and MyoD. Previous studies have suggested that myostatin imposes quiescence on muscle progenitors. Our data suggest that myostatin's effect on muscle progenitors is more complex than previously realized and is likely to be context-dependent. We propose a novel model for myostatin mode of action in vivo, in which myostatin affects the balance between proliferation and differentiation of embryonic muscle progenitors by enhancing their differentiation.

  12. Myostatin promotes the terminal differentiation of embryonic muscle progenitors

    PubMed Central

    Manceau, Marie; Gros, Jérôme; Savage, Kathleen; Thomé, Virginie; McPherron, Alexandra; Paterson, Bruce; Marcelle, Christophe

    2008-01-01

    Myostatin, a TGF-β family member, is an important regulator of adult muscle size. While extensively studied in vitro, the mechanisms by which this molecule mediates its effect in vivo are poorly understood. We addressed this question using chick and mouse embryos. We show that while myostatin overexpression in chick leads to an exhaustion of the muscle progenitor population that ultimately results in muscle hypotrophy, myostatin loss of function in chick and mouse provokes an expansion of this population. Our data demonstrate that myostatin acts in vivo to regulate the balance between proliferation and differentiation of embryonic muscle progenitors by promoting their terminal differentiation through the activation of p21 and MyoD. Previous studies have suggested that myostatin imposes quiescence on muscle progenitors. Our data suggest that myostatin’s effect on muscle progenitors is more complex than previously realized and is likely to be context-dependent. We propose a novel model for myostatin mode of action in vivo, in which myostatin affects the balance between proliferation and differentiation of embryonic muscle progenitors by enhancing their differentiation. PMID:18316481

  13. Emergence of neuronal diversity from patterning of telencephalic progenitors.

    PubMed

    Azzarelli, Roberta; Hardwick, Laura J A; Philpott, Anna

    2015-01-01

    During central nervous system (CNS) development, hundreds of distinct neuronal subtypes are generated from a single layer of multipotent neuroepithelial progenitor cells. Within the rostral CNS, initial regionalization of the telencephalon marks the territories where the cerebral cortex and the basal ganglia originate. Subsequent refinement of the primary structures determines the formation of domains of differential gene expression, where distinct fate-restricted progenitors are located. To understand how diversification of neural progenitors and neurons is achieved in the telencephalon, it is important to address early and late patterning events in this context. In particular, important questions include: How does the telencephalon become specified and regionalized along the major spatial axes? Within each region, are the differences in neuronal subtypes established at the progenitor level or at the postmitotic stage? If distinct progenitors exist that are committed to subtype-specific neuronal lineages, how does the diversification emerge? What is the contribution of positional and temporal cues and how is this information integrated into the intrinsic programs of cell identity? WIREs For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

  14. Isolation of resident cardiac progenitor cells by Hoechst 33342 staining.

    PubMed

    Pfister, Otmar; Oikonomopoulos, Angelos; Sereti, Konstantina-Ioanna; Liao, Ronglih

    2010-01-01

    Cardiac resident stem/progenitor cells are critical to the cellular and functional integrity of the heart by maintaining myocardial cell homeostasis. Given their central role in myocardial biology, resident cardiac progenitor cells have become a major focus in cardiovascular research. Identification of putative cardiac progenitor cells within the myocardium is largely based on the presence or absence of specific cell surface markers. Additional purification strategies take advantage of the ability of stem cells to efficiently efflux vital dyes such as Hoechst 33342. During fluoresence activated cell sorting (FACS) such Hoechst-extruding cells appear to the side of Hoechst-dye retaining cells and have thus been termed side population (SP) cells. We have shown that cardiac SP cells that express stem cell antigen 1 (Sca-1) but not CD31 are cardiomyogenic, and thus represent a putative cardiac progenitor cell population. This chapter describes the methodology for the isolation of resident cardiac progenitor cells utilizing the SP phenotype combined with stem cell surface markers.

  15. 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.

  16. A Postnatal Pax7+ Progenitor Gives Rise to Pituitary Adenomas

    PubMed Central

    Hosoyama, Tohru; Nishijo, Koichi; Garcia, Melinda M.; Schaffer, Beverly S.; Ohshima-Hosoyama, Sachiko; Prajapati, Suresh I.; Davis, Michael D.; Grant, Wilmon F.; Scheithauer, Bernd W.; Marks, Daniel L.; Rubin, Brian P.; Keller, Charles

    2010-01-01

    Pituitary adenomas are classified into functioning and nonfunctioning (silent) tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis and the cell of origin for pituitary adenoma subtypes remain to be elucidated. Employing a tamoxifen-inducible mouse model, we demonstrate that a novel postnatal Pax7+ progenitor cell population in the pituitary gland gives rise to silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is conditionally deleted. While Pax transcriptional factors are critical for embryonic patterning as well as postnatal stem cell renewal for many organs, we have discovered that Pax7 marks a restricted cell population in the postnatal pituitary intermediate lobe. This Pax7+ early progenitor cell population is overlapping but ontologically downstream of the Nestin+ pituitary stem cell population, yet upstream of another newly discovered Myf6+ late progenitor cell population. Interestingly, the Pax7+ progenitor cell population is evolutionarily conserved in primates and humans, and Pax7 expression is maintained not only in murine tumors but also in human functioning and silent corticotropinomas. Taken together, our results strongly suggest that human silent corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate lobe, a region of the human pituitary bearing closer scientific interest as a reservoir of pituitary progenitor cells. PMID:20811506

  17. Vascular wall progenitor cells in health and disease.

    PubMed

    Psaltis, Peter J; Simari, Robert D

    2015-04-10

    The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease. © 2015 American Heart Association, Inc.

  18. NFIX regulates neural progenitor cell differentiation during hippocampal morphogenesis.

    PubMed

    Heng, Yee Hsieh Evelyn; McLeay, Robert C; Harvey, Tracey J; Smith, Aaron G; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M; Bailey, Timothy L; Richards, Linda J; Piper, Michael

    2014-01-01

    Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix(-/-) mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix(-/-) mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix(-/-) mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure.

  19. 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.

  20. Type Ia Supernovae Keep Memory of their Progenitor Metallicity

    NASA Astrophysics Data System (ADS)

    Piersanti, Luciano; Bravo, Eduardo; Cristallo, Sergio; Domínguez, Inmaculada; Straniero, Oscar; Tornambé, Amedeo; Martínez-Pinedo, Gabriel

    2017-02-01

    The ultimate understanding of SNe Ia diversity is one of the most urgent issues to exploit thermonuclear explosions of accreted White Dwarfs (WDs) as cosmological yardsticks. In particular, we investigate the impact of the progenitor system metallicity on the physical and chemical properties of the WD at the explosion epoch. We analyze the evolution of CO WDs through the accretion and simmering phases by using evolutionary models based on time-dependent convective mixing and an extended nuclear network including the most important electron captures, beta decays, and URCA processes. We find that, due to URCA processes and electron-captures, the neutron excess and density at which the thermal runaway occurs are substantially larger than previously claimed. Moreover, we find that the higher the progenitor metallicity, the larger the neutron excess variation during the accretion and simmering phases and the higher the central density and the convective velocity at the explosion. Hence, the simmering phase acts as an amplifier of the differences existing in SNe Ia progenitors. When applying our results to the neutron excess estimated for the Tycho and Kepler young supernova remnants, we derive that the metallicity of the progenitors should be in the range Z=0.030{--}0.032, close to the average metallicity value of the thin disk of the Milky Way. As the amount of {}56{Ni} produced in the explosion depends on the neutron excess and central density at the thermal runaway, our results suggest that the light curve properties depend on the progenitor metallicity.

  1. High fat diet enhances stemness and tumorigenicity of intestinal progenitors

    PubMed Central

    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.

    2016-01-01

    Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (non-ISC) progenitor cells, and pharmacologic activation of PPAR-d 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-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoid-initiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors. PMID:26935695

  2. Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration.

    PubMed

    Singh, Sarvjeet; Canseco, Diana C; Manda, Shilpa M; Shelton, John M; Chirumamilla, Rajendra R; Goetsch, Sean C; Ye, Qiu; Gerard, Robert D; Schneider, Jay W; Richardson, James A; Rothermel, Beverly A; Mammen, Pradeep P A

    2014-01-07

    Mammalian skeletal muscle can remodel, repair, and regenerate itself by mobilizing satellite cells, a resident population of myogenic progenitor cells. Muscle injury and subsequent activation of myogenic progenitor cells is associated with oxidative stress. Cytoglobin is a hemoprotein expressed in response to oxidative stress in a variety of tissues, including striated muscle. In this study, we demonstrate that cytoglobin is up-regulated in activated myogenic progenitor cells, where it localizes to the nucleus and contributes to cell viability. siRNA-mediated depletion of cytoglobin from C2C12 myoblasts increased levels of reactive oxygen species and apoptotic cell death both at baseline and in response to stress stimuli. Conversely, overexpression of cytoglobin reduced reactive oxygen species levels, caspase activity, and cell death. Mice in which cytoglobin was knocked out specifically in skeletal muscle were generated to examine the role of cytoglobin in vivo. Myogenic progenitor cells isolated from these mice were severely deficient in their ability to form myotubes as compared with myogenic progenitor cells from wild-type littermates. Consistent with this finding, the capacity for muscle regeneration was severely impaired in mice deficient for skeletal-muscle cytoglobin. Collectively, these data demonstrate that cytoglobin serves an important role in muscle repair and regeneration.

  3. 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.

  4. 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. Copyright © 2014 the American Physiological Society.

  5. 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

  6. Identification of a common mesenchymal stromal progenitor for the adult haematopoietic niche

    PubMed Central

    Hu, Xingbin; Garcia, Mayra; Weng, Lihong; Jung, Xiaoman; Murakami, Jodi L.; Kumar, Bijender; Warden, Charles D.; Todorov, Ivan; Chen, Ching-Cheng

    2016-01-01

    Microenvironment cues received by haematopoietic stem cells (HSC) are important in regulating the choice between self-renewal and differentiation. On the basis of the differential expression of cell-surface markers, here we identify a mesenchymal stromal progenitor hierarchy, where CD45−Ter119−CD31−CD166−CD146−Sca1+(Sca1+) progenitors give rise to CD45−Ter119−CD31−CD166−CD146+(CD146+) intermediate and CD45−Ter119−CD31−CD166+CD146−(CD166+) mature osteo-progenitors. All three progenitors preserve HSC long-term multi-lineage reconstitution capability in vitro; however, their in vivo fates are different. Post-transplantation, CD146+ and CD166+ progenitors form bone only. While Sca1+ progenitors produce CD146+, CD166+ progenitors, osteocytes and CXCL12-producing stromal cells. Only Sca1+ progenitors are capable of homing back to the marrow post-intravenous infusion. Ablation of Sca1+ progenitors results in a decrease of all three progenitor populations as well as haematopoietic stem/progenitor cells. Moreover, suppressing production of KIT-ligand in Sca1+ progenitors inhibits their ability to support HSCs. Our results indicate that Sca1+ progenitors, through the generation of both osteogenic and stromal cells, provide a supportive environment for hematopoiesis. PMID:27721421

  7. 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

  8. Rates and progenitors of type Ia supernovae

    SciTech Connect

    Wood-Vasey, William Michael

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 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.

  9. 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

  10. Neural progenitors, neurogenesis and the evolution of the neocortex.

    PubMed

    Florio, Marta; Huttner, Wieland B

    2014-06-01

    The neocortex is the seat of higher cognitive functions and, in evolutionary terms, is the youngest part of the mammalian brain. Since its origin, the neocortex has expanded in several mammalian lineages, and this is particularly notable in humans. This expansion reflects an increase in the number of neocortical neurons, which is determined during development and primarily reflects the number of neurogenic divisions of distinct classes of neural progenitor cells. Consequently, the evolutionary expansion of the neocortex and the concomitant increase in the numbers of neurons produced during development entail interspecies differences in neural progenitor biology. Here, we review the diversity of neocortical neural progenitors, their interspecies variations and their roles in determining the evolutionary increase in neuron numbers and neocortex size.

  11. Vascular stem/progenitor cells: functions and signaling pathways.

    PubMed

    Lu, Weisi; Li, Xuri

    2017-09-27

    Vascular stem/progenitor cells (VSCs) are an important source of all types of vascular cells needed to build, maintain, repair, and remodel blood vessels. VSCs, therefore, play critical roles in the development, normal physiology, and pathophysiology of numerous diseases. There are four major types of VSCs, including endothelial progenitor cells (EPCs), smooth muscle progenitor cells (SMPCs), pericytes, and mesenchymal stem cells (MSCs). VSCs can be found in bone marrow, circulating blood, vessel walls, and other extravascular tissues. During the past two decades, considerable progress has been achieved in the understanding of the derivation, surface markers, and differentiation of VSCs. Yet, the mechanisms regulating their functions and maintenance under normal and pathological conditions, such as in eye diseases, remain to be further elucidated. Owing to the essential roles of blood vessels in human tissues and organs, understanding the functional properties and the underlying molecular basis of VSCs is of critical importance for both basic and translational research.

  12. Wnt2 regulates progenitor proliferation in the developing ventral midbrain.

    PubMed

    Sousa, Kyle M; Villaescusa, J Carlos; Cajanek, Lukas; Ondr, Jennifer K; Castelo-Branco, Goncalo; Hofstra, Wytske; Bryja, Vitezslav; Palmberg, Carina; Bergman, Tomas; Wainwright, Brandon; Lang, Richard A; Arenas, Ernest

    2010-03-05

    Wnts are secreted, lipidated proteins that regulate multiple aspects of brain development, including dopaminergic neuron development. In this study, we perform the first purification and signaling analysis of Wnt2 and define the function of Wnt2 in ventral midbrain precursor cultures, as well as in Wnt2-null mice in vivo. We found that purified Wnt2 induces the phosphorylation of both Lrp5/6 and Dvl-2/3, and activates beta-catenin in SN4741 dopaminergic cells. Moreover, purified Wnt2 increases progenitor proliferation, and the number of dopaminergic neurons in ventral midbrain precursor cultures. In agreement with these findings, analysis of the ventral midbrain of developing Wnt2-null mice revealed a decrease in progenitor proliferation and neurogenesis that lead to a decrease in the number of postmitotic precursors and dopaminergic neurons. Collectively, our observations identify Wnt2 as a novel regulator of dopaminergic progenitors and dopaminergic neuron development.

  13. Advances in hepatic stem/progenitor cell biology

    PubMed Central

    Verhulst, Stefaan; Best, Jan; van Grunsven, Leo A.; Dollé, Laurent

    2015-01-01

    The liver is famous for its strong regenerative capacity, employing different modes of regeneration according to type and extent of injury. Mature liver cells are able to proliferate in order to replace the damaged tissue allowing the recovery of the parenchymal function. In more severe scenarios hepatocytes are believed to arise also from a facultative liver progenitor cell compartment. In human, severe acute liver failure and liver cirrhosis are also both important clinical targets in which regeneration is impaired, where the role of this stem cell compartment seems more convincing. In animal models, the current state of ambiguity regarding the identity and role of liver progenitor cells in liver physiology dampens the enthusiasm for the potential use of these cells in regenerative medicine. The aim of this review is to give the basics of liver progenitor cell biology and discuss recent results vis-à-vis their identity and contribution to liver regeneration. PMID:26600740

  14. Establishment of bipotent progenitor cell clone from rat skeletal muscle.

    PubMed

    Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  15. In vitro toxicity of trichothecenes on rat haematopoietic progenitors.

    PubMed

    Parent-Massin, D; Thouvenot, D

    1995-01-01

    The fusarial toxicosis induced by trichothecenes is characterized by common syndromes such as vomiting, inflammation, haemorrhages, diarrhoea and haematological changes. Subchronic ingestion of trichothecenes causes a decrease in circulating white cells. This leukopenic change of animals is reported as a characteristic feature in the best known human disorder: Alimentary Toxic Aleukia (ATA). The aim of the present study was to evaluate whether the haematologic disorders imputed to trichothecenes were a result of myelotoxicity by investigating in an in vitro model. Rat haematopoietic progenitors, Colony Forming Units-Granulocytes and Macrophages (CFU-GM), were cultured in the presence of several concentrations of four trichothecenes; T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON). All these trichothecenes were cytotoxic to rat haematopoietic progenitor cells. It is concluded that haematological disorders observed during trichothecene intoxication of animals are caused by the destruction of haematopoietic progenitors such as CFU-GM cells.

  16. Wnt2 Regulates Progenitor Proliferation in the Developing Ventral Midbrain*

    PubMed Central

    Sousa, Kyle M.; Villaescusa, J. Carlos; Cajanek, Lukas; Ondr, Jennifer K.; Castelo-Branco, Goncalo; Hofstra, Wytske; Bryja, Vitezslav; Palmberg, Carina; Bergman, Tomas; Wainwright, Brandon; Lang, Richard A.; Arenas, Ernest

    2010-01-01

    Wnts are secreted, lipidated proteins that regulate multiple aspects of brain development, including dopaminergic neuron development. In this study, we perform the first purification and signaling analysis of Wnt2 and define the function of Wnt2 in ventral midbrain precursor cultures, as well as in Wnt2-null mice in vivo. We found that purified Wnt2 induces the phosphorylation of both Lrp5/6 and Dvl-2/3, and activates β-catenin in SN4741 dopaminergic cells. Moreover, purified Wnt2 increases progenitor proliferation, and the number of dopaminergic neurons in ventral midbrain precursor cultures. In agreement with these findings, analysis of the ventral midbrain of developing Wnt2-null mice revealed a decrease in progenitor proliferation and neurogenesis that lead to a decrease in the number of postmitotic precursors and dopaminergic neurons. Collectively, our observations identify Wnt2 as a novel regulator of dopaminergic progenitors and dopaminergic neuron development. PMID:20018874

  17. CXCR4 Expression in Prostate Cancer Progenitor Cells

    PubMed Central

    Dubrovska, Anna; Elliott, Jimmy; Salamone, Richard J.; Telegeev, Gennady D.; Stakhovsky, Alexander E.; Schepotin, Ihor B.; Yan, Feng; Wang, Yan; Bouchez, Laure C.; Kularatne, Sumith A.; Watson, James; Trussell, Christopher; Reddy, Venkateshwar A.; Cho, Charles Y.; Schultz, Peter G.

    2012-01-01

    Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44+/CD133+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy. PMID:22359577

  18. Purification of Clostridium botulinum Type F Progenitor Toxin

    PubMed Central

    Ohishi, Iwao; Sakaguchi, Genji

    1974-01-01

    Clostridium botulinum type F progenitor toxin was purified to a homogeneous state as judged by gel filtration on Sephadex G-200, ultracentrifugation, and disc electrophoresis. The sedimentation constant, corrected to water at 20 C, of type F progenitor toxin was determined to be 10.3 and the molecular weight to be 235,000 by ultracentrifugation at pH 6.0. The purified toxin contained a toxicity of 1.2 × 108 50% lethal doses/mg of N. In agar gel double diffusion, it formed two precipitin lines at pH 6.0. The progenitor toxin of type F differs from that of type A in that it contains no hemagglutinin and from that of type E in that it is not activable. Images PMID:4615636

  19. Suppressive activity of acivicin on murine bone marrow hemopoietic progenitors.

    PubMed

    Castello, G; Mencoboni, M; Lerza, R; Cerruti, A; Bogliolo, G; Pannacciulli, I

    1992-01-01

    Acivicin (AVC), a L-glutamine antagonist, is an intriguing antimetabolite coupling cell growth inhibition activity with differentiating effects. In this in vivo study the influence of acivicin on mice bone marrow hemopoietic progenitors was tested. 10 mg/kg b.w./day of acivicin were i.p. injected in B6D2F1 mice for nine days. Leucocyte and reticulocyte level (in peripheral blood), CFU-S (multipotent stem cells) and GM-CFU (granulocyte-macrophage committed progenitors) content in bone marrow were determined during drug administration and for 14 days thereafter. All tested populations decreased severely during the first days of treatment. The drop was particularly striking for bone marrow CFU-S. The recovery of hemopoietic progenitors, however, began while AVC was still administered. These results suggest that the effects of acivicin on normal mouse hemopoietic system are mainly inhibitory, causing considerable myelosuppression.

  20. Close Binary Progenitors and Ejected Companions of Thermonuclear Supernovae

    NASA Astrophysics Data System (ADS)

    Geier, S.; Kupfer, T.; Heber, U.; Nemeth, P.; Ziegerer, E.; Irrgang, A.; Schindewolf, M.; Marsh, T. R.; Gänsicke, B. T.; Barlow, B. N.; Bloemen, S.

    2017-03-01

    Hot subdwarf stars (sdO/Bs) are evolved core helium-burning stars with very thin hydrogen envelopes, which can be formed by common envelope ejection. Close sdB binaries with massive white dwarf (WD) companions are potential progenitors of thermonuclear supernovae type Ia (SN Ia). We discovered such a progenitor candidate as well as a candidate for a surviving companion star, which escapes from the Galaxy. More candidates for both types of objects have been found by cross-matching known sdB stars with proper motion and light curve catalogues. We found 72 sdO/B candidates with high Galactic restframe velocities, 12 of them might be unbound to our Galaxy. Furthermore, we discovered the second-most compact sdB+WD binary known. However, due to the low mass of the WD companion, it is unlikely to be a SN Ia progenitor.

  1. Searching for the Progenitors of Type Ia Supernova

    NASA Astrophysics Data System (ADS)

    Di Stefano, Rosanne

    2011-05-01

    Type Ia supernovae are important cosmic probes. To understand and eliminate systematic uncertainties, it is important to know the nature and characteristics of their progenitors. I will talk about recent progress that may allow us to search for and identify progenitors within our own Galaxy, using data from wide-field surveys such as SDSS, Pan-STARRS, and LSST. We will consider the nuclear-burning phase that is expected to occur in both single-degenerate and double-degenerate models. We will also consider the expected characteristics just prior to explosion in the new class of spin-up/spin-down models. Finally, we will discuss the prospects for finding the progenitors in external galaxies, in light of the fact that most do not appear as x-ray sources, or else have a low duty cycle of x-ray activity.

  2. Telomerase extends a helping hand to progenitor cells.

    PubMed

    Natesan, Sridaran

    2005-01-01

    The idea of a cell-based regeneration therapy for controlling or curing chronic human diseases is highly attractive. However, realization of this idea in the clinic has been hampered by the safety concerns associated with the transplantation of immortalized cells into human patients. An elegant study done by Roy and colleagues shows that neural progenitor cells immortalized by the ectopic expression of telomerase reverse transcriptase (TERT) can give rise to specific types of functionally competent neurons both in vitro and in vivo. Importantly, the immortalized progenitors maintained their phenotype with no evidence of transformation even several months after transplantation in mouse disease models. Although the potential use of telomerase-immortalized cells in the clinic remains controversial, Roy and colleagues work provides a compelling reason to seriously evaluate the potential use of telomerase-immortalized progenitor cells to treat neurodegenerative and other chronic human illnesses.

  3. 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

  4. 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

  5. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes

    PubMed Central

    Pang, Wendy W.; Pluvinage, John V.; Price, Elizabeth A.; Sridhar, Kunju; Arber, Daniel A.; Greenberg, Peter L.; Schrier, Stanley L.; Park, Christopher Y.; Weissman, Irving L.

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of disorders characterized by variable cytopenias and ineffective hematopoiesis. Hematopoietic stem cells (HSCs) and myeloid progenitors in MDS have not been extensively characterized. We transplanted purified human HSCs from MDS samples into immunodeficient mice and show that HSCs are the disease-initiating cells in MDS. We identify a recurrent loss of granulocyte-macrophage progenitors (GMPs) in the bone marrow of low risk MDS patients that can distinguish low risk MDS from clinical mimics, thus providing a simple diagnostic tool. The loss of GMPs is likely due to increased apoptosis and increased phagocytosis, the latter due to the up-regulation of cell surface calreticulin, a prophagocytic marker. Blocking calreticulin on low risk MDS myeloid progenitors rescues them from phagocytosis in vitro. However, in the high-risk refractory anemia with excess blasts (RAEB) stages of MDS, the GMP population is increased in frequency compared with normal, and myeloid progenitors evade phagocytosis due to up-regulation of CD47, an antiphagocytic marker. Blocking CD47 leads to the selective phagocytosis of this population. We propose that MDS HSCs compete with normal HSCs in the patients by increasing their frequency at the expense of normal hematopoiesis, that the loss of MDS myeloid progenitors by programmed cell death and programmed cell removal are, in part, responsible for the cytopenias, and that up-regulation of the “don’t eat me” signal CD47 on MDS myeloid progenitors is an important transition step leading from low risk MDS to high risk MDS and, possibly, to acute myeloid leukemia. PMID:23388639

  6. Apoptotic lymphocytes induce progenitor cell mobilization after exercise.

    PubMed

    Mooren, Frank C; Krüger, Karsten

    2015-07-15

    There is evidence that apoptotic cells and their components have immunmodulatory properties and signaling function. The present study investigated first whether exercise-induced apoptosis and exercise-induced mobilization of progenitor cells are similarly affected by subjects' training status and, second, whether the appearance of dying cells in the circulation might mobilize progenitor cells. CD1 SWISS mice were subjected to a 10-wk endurance training using free wheel running or served as untrained controls. Mice of both groups performed an intensive exercise test after the training period at a velocity corresponding to 80% maximal oxygen uptake for 30 min. Cells from blood and bone marrow were analyzed, and apoptosis and number of progenitor cells determined via flow cytometry. In a second experiment, apoptotic cells were transferred into recipient mice, and mobilization of progenitor cells was analyzed while vital cells served as controls. In untrained animals, the exhaustive exercise was followed by an enhanced rate of annexin V positive CD3(+) cells in blood and bone marrow (P < 0.05), whereas no increase was found in trained mice. Similarly, exercise mobilized Sca-1(+)/c-kit(+) and Sca-1(+)/Flk(+) cells in untrained (P < 0.05) but not trained mice. Furthermore, application of apoptotic cells and their supernatant mobilized Sca-1(+)/c-kit(+) cells into the blood (P < 0.05), whereas Sca-1(+)/Flk(+) cells were not affected. The present study demonstrated that both lymphocyte apoptosis, as well as mobilization of progenitor cells are similarly related to training status. Furthermore, apoptotic cells seem to induce signals that effectively mobilize hematopoietic progenitor cells. The relevance of this effect for the adaptation to exercise stimuli remains to be shown. Copyright © 2015 the American Physiological Society.

  7. 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.

  8. Endothelial progenitor cells: a new player in lupus?

    PubMed

    Haque, Sahena; Alexander, M Yvonne; Bruce, Ian N

    2012-02-20

    Patients with systemic lupus erythematosus (SLE) have a greatly increased risk of cardiovascular disease. There is growing interest in the link between vascular damage and lupus-specific inflammatory factors. Impaired endothelial repair could account for the endothelial dysfunction in this patient group. This review describes the contribution that endothelial progenitor cells could play in the pathogenesis of premature vascular damage in this disease. The methods of isolation, detection, and characterization of endothelial progenitor cells, together with their potential role in repair of the endothelium and as a therapeutic target in SLE, are discussed.

  9. Stem and progenitor cells: the premature desertion of rigorous definitions.

    PubMed

    Seaberg, Raewyn M; van der Kooy, Derek

    2003-03-01

    A current disturbing trend in stem cell biology is the abandonment of rigorous definitions of stem and progenitor cells in favor of more ambiguous, all-encompassing concepts. However, recent studies suggest that there are consistent, functional differences in the biology of these two cell types. Admittedly, it can be difficult to harmonize the in vivo and in vitro functional differences between stem and progenitor cells. Nonetheless, these distinctions between cell types should be emphasized rather than ignored, as they can be used to test specific hypotheses in neural stem cell biology.

  10. Systematic Features and Progenitor Dependence of Core-Collapse Supernovae

    NASA Astrophysics Data System (ADS)

    Nakamura, Ko; Takiwaki, Tomoya; Kuroda, Takami; Kotake, Kei

    We present our latest results of two-dimensional core-collapse supernova simulations for about 400 progenitors. Our self-consistent supernova models reveal the systematic features of core-collapse supernova properties such as neutrino luminosity and energy spectrum, explosion energy, remnant mass, and yield of radioactive 56Ni. We find that these explosion characteristics tend to show a monotonic increase as a function of mass accretion rate onto a shock. The accretion rate depends on the structure of the progenitor core and its envelope, which is well described by the compactness parameter.

  11. 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.

  12. Stress-Induced Premature Senescence of Endothelial and Endothelial Progenitor Cells

    PubMed Central

    Goligorsky, M.S.; Hirschi, K.

    2016-01-01

    This brief overview of premature senescence of dysfunctional endothelial and endothelial progenitor cells provides information on endothelial cell differentiation and specialization, their ontogeny, and controversies related to endothelial stem and progenitor cells. Stressors responsible for the dysfunction of endothelial and endothelial progenitor cells, as well as cellular mechanisms and consequences of endothelial cell dysfunction are presented. Metabolic signatures of dysfunctional endothelial cells and senescence pathways are described. Emerging strategies to rejuvenate endothelial and endothelial progenitor cells conclude the review. PMID:27451101

  13. 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.

  14. Oral mucosal progenitor cell clones resist in vitro myogenic differentiation.

    PubMed

    Locke, Matthew; Davies, Lindsay C; Stephens, Phil

    2016-10-01

    Progenitor cells derived from the oral mucosa lamina propria (OMLP-PCs) demonstrate an ability to differentiate into tissue lineages removed from their anatomical origin. This clonally derived population of neural-crest cells have demonstrated potential to differentiate along mesenchymal and neuronal cell lineages.

  15. Progenitor Candidate for SN 2016gkg in NGC 613

    NASA Astrophysics Data System (ADS)

    Kilpatrick, C. D.; Siebert, M. R.; Foley, R. J.; Max, C. E.; Williams, P.; Abramson, L. E.; Lu, C.-X.; Treu, T.; Kassis, M.

    2016-09-01

    We have identified a candidate progenitor star of the Type II SN 2016gkg in NGC 613 (ATel #9521, #9526, #9528, #9529) in archival Hubble Space Telescope (HST) WFPC2 images in the F450W, F606W, and F814W filters.

  16. [Research and clinical applications regarding endothelial progenitor cell transplantation].

    PubMed

    Tan, Kefang; Sun, Xuan

    2014-11-01

    Endothelial injury or dysfunction leads to multiple cardiovascular diseases, such as atherosclerosis, myocardial infarction, stroke, hypertension and peripheral vascular disease. Endothelial progenitor cells (EPCs) are precursor cells of endothelial cells, including the early endothelial progenitor cells and the late endothelial progenitor cells. These two EPC types have different function and surface markers. EPC in this article mainly means late endothelial progenitors which could grow into endothelial cloning and form vessels in vivo. Late EPCs can express CD133, CD31, KDR, CD144, CD34 etc, take in low density lipoprotein, bind with ulex europaeus lectin 1 and form blood vessels in vitro and in vivo. EPCs not only participate in new blood vessels formation, but also are closely related to the repair of damaged endothelium. Many studies confirm that the transplanted EPCs are able to be mobilized to vascular injury location and repair the damaged endothelial cells thus promote new blood vessel formation, which provides a promising strategy for the treatment of cardiovascular diseases and ischemic diseases.

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

    PubMed

    Bye, Chris R; Jönsson, Marie E; Björklund, Anders; Parish, Clare L; Thompson, Lachlan H

    2015-04-14

    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.

  18. Early patterning and specification of cardiac progenitors in gastrulating mesoderm

    PubMed Central

    Devine, W Patrick; Wythe, Joshua D; George, Matthew; Koshiba-Takeuchi, Kazuko; Bruneau, Benoit G

    2014-01-01

    Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor ‘fields’ has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies. DOI: http://dx.doi.org/10.7554/eLife.03848.001 PMID:25296024

  19. Foetal and adult cardiomyocyte progenitor cells have different developmental potential

    PubMed Central

    Van Vliet, Patrick; Smits, Anke M; De Boer, Teun P; Korfage, Tom H; Metz, Corina HG; Roccio, Marta; Van Der Heyden, Marcel AG; Van Veen, Toon AB; Sluijter, Joost PG; Doevendans, Pieter A; Goumans, Marie-José

    2010-01-01

    Abstract In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. Up to date, no studies have been reported in which the developmental potential of foetal and adult cardiovascular progenitors was tested simultaneously. However, intrinsic differences will likely affect interpretations regarding progenitor cell potential and application for regenerative medicine. Here we report a direct comparison between human foetal and adult heart-derived cardiomyocyte progenitor cells (CMPCs). We show that foetal and adult CMPCs have distinct preferences to differentiate into mesodermal lineages. Under pro-angiogenic conditions, foetal CMPCs form more endothelial but less smooth muscle cells than adult CMPCs. Foetal CMPCs can also develop towards adipocytes, whereas neither foetal nor adult CMPCs show significant osteogenic differentiation. Interestingly, although both cell types differentiate into heart muscle cells, adult CMPCs give rise to electrophysiologically more mature cardiomyocytes than foetal CMPCs. Taken together, foetal CMPCs are suitable for molecular cell biology and developmental studies. The potential of adult CMPCs to form mature cardiomyocytes and smooth muscle cells may be essential for cardiac repair after transplantation into the injured heart. PMID:20219011

  20. TYPE IIb SUPERNOVAE WITH COMPACT AND EXTENDED PROGENITORS

    SciTech Connect

    Chevalier, Roger A.; Soderberg, Alicia M.

    2010-03-01

    The classic example of a Type IIb supernova is SN 1993J, which had a cool extended progenitor surrounded by a dense wind. There is evidence for another category of Type IIb supernova that has a more compact progenitor with a lower density, probably fast, wind. Distinguishing features of the compact category are weak optical emission from the shock heated envelope at early times, nonexistent or very weak H emission in the late nebular phase, rapidly evolving radio emission, rapid expansion of the radio shell, and expected nonthermal as opposed to thermal X-ray emission. Type IIb supernovae that have one or more of these features include SNe 1996cb, 2001ig, 2003bg, 2008ax, and 2008bo. All of these with sufficient radio data (the last four) show evidence for presupernova wind variability. We estimate a progenitor envelope radius {approx}1 x 10{sup 11} cm for SN 2008ax, a value consistent with a compact Wolf-Rayet progenitor. Supernovae in the SN 1993J extended category include SN 2001gd and probably the Cas A supernova. We suggest that the compact Type IIb events be designated Type cIIb and the extended ones Type eIIb. The H envelope mass dividing these categories is {approx}0.1 M {sub sun}.

  1. Flow cytometric data analysis of circulating progenitor cell stability.

    PubMed

    Mahar, Ernestine A; Mou, Liping; Hayek, Salim S; Quyyumi, Arshed A; Waller, Edmund K

    2017-02-01

    A recent publication by Mekonnen et al. demonstrated that among women with non-obstructive coronary artery disease, higher levels of circulating progenitor cells in the blood (CPC), were associated with impaired coronary flow reserve [1]. We performed a quality control assessment of the stability of circulating blood progenitor cells in blood samples stored at 4 °C, to determine the time period during which blood samples can be analyzed and yield consistent data for progenitor cell content. Healthy volunteers (n=6) were recruited and underwent phlebotomy, and blood was stored in EDTA tubes at 4 °C. Flow cytometry was performed to quantitate progenitor cell subsets at 0-4 h, 24 h, and 48 h post phlebotomy. All processed samples were fixed with 1% Paraformaldehyde and 1,000,000 total data events were collected. We found no significant differences in PC data for both CD34+ (P=0.68 for one-way ANOVA) and CD34+/CD133+ (P=0.74 for one-way ANOVA).

  2. Repair of injured proximal tubule does not involve specialized progenitors

    PubMed Central

    Humphreys, Benjamin D.; Czerniak, Suzanne; DiRocco, Derek P.; Hasnain, Wirasat; Cheema, Rabia; Bonventre, Joseph V.

    2011-01-01

    Recently we have established that the kidney tubular epithelium is repaired by surviving epithelial cells. It is not known, however, whether a population of intratubular adult progenitor cells are responsible for this epithelial repair after acute kidney injury. In this study, we used an unbiased DNA analog-based approach that does not rely on candidate markers to track multiple rounds of cell division in vivo. In the proximal tubule, robust thymidine analog incorporation was observed postinjury. Cell division was stochastic and enriched among cells that were injured and dedifferentiated. There was no evidence for the presence of a population of specialized progenitors that repeatedly divide in response to injury. Instead, these results indicate that after injury, new epithelial cells arise from self-duplication of surviving cells, most of which are injured. Because the renal papilla contains DNA label-retaining cells and has been proposed as a stem cell niche, we examined the proliferative behavior of these putative progenitors after ischemia-reperfusion injury. Although label-retaining cells in the renal papilla diminished with time after ischemia-reperfusion injury, they neither proliferated nor migrated to the outer medulla or cortex. Thus, nonlethally injured cells repopulate the kidney epithelium after injury in the absence of any specialized progenitor cell population. PMID:21576461

  3. Characterization of Progenitor Cells during Canine Retinal Development

    PubMed Central

    Ávila-García, Mallely; García-Sánchez, Gustavo; Lira-Romero, Esmeralda; Moreno-Mendoza, Norma

    2012-01-01

    We identify the presence of progenitor cells during retinal development in the dog, as this species represents a natural model for studying several breed-specific degenerative retinal disorders. Antibodies to detected progenitor cells (Pax6, C-kit, and nestin) and ganglion cells (BDNF, Brn3a, and Thy1) were used in combination with H3 for the purpose of identifying proliferating cells. Pax6, nestin, C-kit, and H3 were localized mainly in the neuroblastic layer of the retina during the embryonic stage. During the fetal stage, proteins were expressed in the inner neuroblastic layer (INL) as well as in the outer neuroblastic layer; BDNF, Thy1, and Brn3a were also expressed in the INL. During the neonatal stage only C-kit was not expressed. Proliferating cells were present in both undifferentiated and differentiated retina. These results suggest that, during canine retinogenesis, progenitor cells are distributed along the retina and some of these cells remain as progenitor cells of the ganglion cells during the first postnatal days. PMID:22567026

  4. Evolutionary Models for Type Ib/c Supernova Progenitors

    NASA Astrophysics Data System (ADS)

    Yoon, Sung-Chul

    2015-04-01

    SNe Ib/c mark the deaths of hydrogen-deficient massive stars. The evolutionary scenarios for SNe Ib/c progenitors involve many important physical processes including mass loss by winds and its metallicity dependence, stellar rotation, and binary interactions. This makes SNe Ib/c an excellent test bed for stellar evolution theory. We review the main results of evolutionary models for SN Ib/c progenitors available in the literature and their confrontation with recent observations. We argue that the nature of SN Ib/c progenitors can be significantly different for single and binary systems, and that binary evolution models can explain the ejecta masses derived from SN Ib/c light curves, the distribution of SN Ib/c sites in their host galaxies, and the optical magnitudes of the tentative progenitor candidate of iPTF13bvn. We emphasise the importance of early-time observations of light curves and spectra, accurate measurements of helium mass in SN Ib/c ejecta, and systematic studies about the metallicity dependence of SN Ib/c properties, to better constrain theories.

  5. Core-Collapse Supernova Progenitors in Hubble Space Telescope Images

    NASA Astrophysics Data System (ADS)

    van Dyk, Schuyler D.; Li, Weidong; Filippenko, Alexei V.

    Determining which stars give rise to supernovae (SNe) is key to SN research and stellar evolution studies. Without knowledge of SN progenitors, many of the conclusions and inferences made about the connection between SNe and important problems in astrophysics stand on precarious ground. The main obstacle is that a SN leaves few traces of the star that exploded.

  6. A Progenitor Candidate for SN 2017ein in NGC 3938

    NASA Astrophysics Data System (ADS)

    Van Dyk, Schuyler D.; Filippenko, Alexei V.; Fox, Ori D.; Kelly, Patrick L.; Milisavljevic, Dan; Smith, Nathan

    2017-06-01

    We report the identification of a progenitor candidate for the Type Ic SN 2017ein in NGC 3938 (ATel #10434, #10481) in archival Hubble Space Telescope (HST) images obtained with the Wide Field Planetary Camera 2 (WFPC2) on 2007 December 11 UT in bands F555W and F814W, as part of program GO-10877 (PI: A.V. Filippenko).

  7. Human cardiomyocyte progenitor cells: a short history of nearly everything.

    PubMed

    van Vliet, Patrick; Goumans, Marie-José; Doevendans, Pieter A; Sluijter, Joost P G

    2012-08-01

    The high occurrence of cardiac disease in the Western world has driven clinicians and cardiovascular biologists to look for alternative strategies to treat patients. A challenging approach is the use of stem cells to repair the heart, in itself an inspiring thought. In the past 10 years, stem cells from different sources have been under intense investigation and, as a result, a multitude of studies have been published on the identification, isolation, and characterization, of cardiovascular progenitor cells and repair in different animal models. However, relatively few cardiovascular progenitor populations have been identified in human hearts, including, but not limited to, cardiosphere-derived cells, cKit+ human cardiac stem cells , Isl1+ cardiovascular progenitors, and, in our lab, cardiomyocyte progenitor cells (CMPCs). Here, we aim to provide a comprehensive summary of the past findings and present challenges for future therapeutic potential of CMPCs. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  8. 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

  9. Type IIb Supernovae with Compact and Extended Progenitors

    NASA Astrophysics Data System (ADS)

    Chevalier, Roger A.; Soderberg, Alicia M.

    2010-03-01

    The classic example of a Type IIb supernova is SN 1993J, which had a cool extended progenitor surrounded by a dense wind. There is evidence for another category of Type IIb supernova that has a more compact progenitor with a lower density, probably fast, wind. Distinguishing features of the compact category are weak optical emission from the shock heated envelope at early times, nonexistent or very weak H emission in the late nebular phase, rapidly evolving radio emission, rapid expansion of the radio shell, and expected nonthermal as opposed to thermal X-ray emission. Type IIb supernovae that have one or more of these features include SNe 1996cb, 2001ig, 2003bg, 2008ax, and 2008bo. All of these with sufficient radio data (the last four) show evidence for presupernova wind variability. We estimate a progenitor envelope radius ~1 × 1011 cm for SN 2008ax, a value consistent with a compact Wolf-Rayet progenitor. Supernovae in the SN 1993J extended category include SN 2001gd and probably the Cas A supernova. We suggest that the compact Type IIb events be designated Type cIIb and the extended ones Type eIIb. The H envelope mass dividing these categories is ~0.1 M sun.

  10. A Malignant Oligarchy: Progenitors Govern the Behavior of Oligodendrogliomas

    PubMed Central

    Pei, Yanxin; Wechsler-Reya, Robert J.

    2010-01-01

    Recent studies have suggested that brain tumors arise from neural stem cells, and are maintained by stem-like tumor-initiating cells (TICs). In this issue of Cancer Cell Persson et al. report that oligodendrogliomas, unlike malignant astrocytomas, originate from – and are propagated by – cells that resemble oligodendrocyte progenitors. PMID:21156279

  11. A malignant oligarchy: progenitors govern the behavior of oligodendrogliomas.

    PubMed

    Pei, Yanxin; Wechsler-Reya, Robert J

    2010-12-14

    Recent studies have suggested that brain tumors arise from neural stem cells and are maintained by stem-like tumor-initiating cells (TICs). In this issue of Cancer Cell, Persson et al. report that oligodendrogliomas, unlike malignant astrocytomas, originate from-and are propagated by-cells that resemble oligodendrocyte progenitors. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia

    PubMed Central

    Jiang, Qingfei; Crews, Leslie A.; Barrett, Christian L.; Chun, Hye-Jung; Court, Angela C.; Isquith, Jane M.; Zipeto, Maria A.; Goff, Daniel J.; Minden, Mark; Sadarangani, Anil; Rusert, Jessica M.; Dao, Kim-Hien T.; Morris, Sheldon R.; Goldstein, Lawrence S. B.; Marra, Marco A.; Frazer, Kelly A.; Jamieson, Catriona H. M.

    2013-01-01

    The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes that regulate stem cell maintenance. In this study, whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-γ pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive ADAR1 p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. Lentiviral overexpression experiments demonstrate that ADAR1 p150 promotes expression of the myeloid transcription factor PU.1 and induces malignant reprogramming of myeloid progenitors. Moreover, enforced ADAR1 p150 expression was associated with production of a misspliced form of GSK3β implicated in LSC self-renewal. Finally, functional serial transplantation and shRNA studies demonstrate that ADAR1 knockdown impaired in vivo self-renewal capacity of blast crisis CML progenitors. Together these data provide a compelling rationale for developing ADAR1-based LSC detection and eradication strategies. PMID:23275297

  13. ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.

    PubMed

    Jiang, Qingfei; Crews, Leslie A; Barrett, Christian L; Chun, Hye-Jung; Court, Angela C; Isquith, Jane M; Zipeto, Maria A; Goff, Daniel J; Minden, Mark; Sadarangani, Anil; Rusert, Jessica M; Dao, Kim-Hien T; Morris, Sheldon R; Goldstein, Lawrence S B; Marra, Marco A; Frazer, Kelly A; Jamieson, Catriona H M

    2013-01-15

    The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes that regulate stem cell maintenance. In this study, whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-γ pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive ADAR1 p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. Lentiviral overexpression experiments demonstrate that ADAR1 p150 promotes expression of the myeloid transcription factor PU.1 and induces malignant reprogramming of myeloid progenitors. Moreover, enforced ADAR1 p150 expression was associated with production of a misspliced form of GSK3β implicated in LSC self-renewal. Finally, functional serial transplantation and shRNA studies demonstrate that ADAR1 knockdown impaired in vivo self-renewal capacity of blast crisis CML progenitors. Together these data provide a compelling rationale for developing ADAR1-based LSC detection and eradication strategies.

  14. β4 Integrin signaling induces expansion of prostate tumor progenitors

    PubMed Central

    Yoshioka, Toshiaki; Otero, Javier; Chen, Yu; Kim, Young-Mi; Koutcher, Jason A.; Satagopan, Jaya; Reuter, Victor; Carver, Brett; de Stanchina, Elisa; Enomoto, Katsuhiko; Greenberg, Norman M.; Scardino, Peter T.; Scher, Howard I.; Sawyers, Charles L.; Giancotti, Filippo G.

    2013-01-01

    The contextual signals that regulate the expansion of prostate tumor progenitor cells are poorly defined. We found that a significant fraction of advanced human prostate cancers and castration-resistant metastases express high levels of the β4 integrin, which binds to laminin-5. Targeted deletion of the signaling domain of β4 inhibited prostate tumor growth and progression in response to loss of p53 and Rb function in a mouse model of prostate cancer (PB-TAg mice). Additionally, it suppressed Pten loss-driven prostate tumorigenesis in tissue recombination experiments. We traced this defect back to an inability of signaling-defective β4 to sustain self-renewal of putative cancer stem cells in vitro and proliferation of transit-amplifying cells in vivo. Mechanistic studies indicated that mutant β4 fails to promote transactivation of ErbB2 and c-Met in prostate tumor progenitor cells and human cancer cell lines. Pharmacological inhibition of ErbB2 and c-Met reduced the ability of prostate tumor progenitor cells to undergo self-renewal in vitro. Finally, we found that β4 is often coexpressed with c-Met and ErbB2 in human prostate cancers and that combined pharmacological inhibition of these receptor tyrosine kinases exerts antitumor activity in a mouse xenograft model. These findings indicate that the β4 integrin promotes prostate tumorigenesis by amplifying ErbB2 and c-Met signaling in tumor progenitor cells. PMID:23348745

  15. Dual requirement for Pax6 in retinal progenitor cells

    PubMed Central

    Elgart, Michael; Marquardt, Till; Remizova, Lena; Yaron, Orly; Xie, Qing; Cvekl, Ales; Ashery-Padan, Ruth

    2014-01-01

    Throughout the developing central nervous system, pre-patterning of the ventricular zone into discrete neural progenitor domains is one of the predominant strategies used to produce neuronal diversity in a spatially coordinated manner. In the retina, neurogenesis proceeds in an intricate chronological and spatial sequence, yet it remains unclear whether retinal progenitor cells (RPCs) display intrinsic heterogeneity at any given time point. Here, we performed a detailed study of RPC fate upon temporally and spatially confined inactivation of Pax6. Timed genetic removal of Pax6 appeared to unmask a cryptic divergence of RPCs into qualitatively divergent progenitor pools. In the more peripheral RPCs under normal circumstances, Pax6 seemed to prevent premature activation of a photoreceptor-differentiation pathway by suppressing expression of the transcription factor Crx. More centrally, Pax6 contributed to the execution of the comprehensive potential of RPCs: Pax6 ablation resulted in the exclusive generation of amacrine interneurons. Together, these data suggest an intricate dual role for Pax6 in retinal neurogenesis, while pointing to the cryptic divergence of RPCs into distinct progenitor pools. PMID:19004853

  16. The direct identification of core-collapse supernova progenitors.

    PubMed

    Van Dyk, Schuyler D

    2017-10-28

    To place core-collapse supernovae (SNe) in context with the evolution of massive stars, it is necessary to determine their stellar origins. I describe the direct identification of SN progenitors in existing pre-explosion images, particularly those obtained through serendipitous imaging of nearby galaxies by the Hubble Space Telescope I comment on specific cases representing the various core-collapse SN types. Establishing the astrometric coincidence of a SN with its putative progenitor is relatively straightforward. One merely needs a comparably high-resolution image of the SN itself and its stellar environment to perform this matching. The interpretation of these results, though, is far more complicated and fraught with larger uncertainties, including assumptions of the distance to and the extinction of the SN, as well as the metallicity of the SN environment. Furthermore, existing theoretical stellar evolutionary tracks exhibit significant variations one from the next. Nonetheless, it appears fairly certain that Type II-P (plateau) SNe arise from massive stars in the red supergiant phase. Many of the known cases are associated with subluminous Type II-P events. The progenitors of Type II-L (linear) SNe are less established. Among the stripped-envelope SNe, there are now a number of examples of cool, but not red, supergiants (presumably in binaries) as Type IIb progenitors. We appear now finally to have an identified progenitor of a Type Ib SN, but no known example yet for a Type Ic. The connection has been made between some Type IIn SNe and progenitor stars in a luminous blue variable phase, but that link is still thin, based on direct identifications. Finally, I also describe the need to revisit the SN site, long after the SN has faded, to confirm the progenitor identification through the star's disappearance and potentially to detect a putative binary companion that may have survived the explosion.This article is part of the themed issue 'Bridging the gap: from

  17. 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

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

    PubMed

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

    2016-01-01

    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. The published literature was searched using the PubMed database with the search terms 'endometrial stem cells and menstrual blood stem cells' until December 2014. 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's syndrome

  19. 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.

  20. Gain of Olig2 function in oligodendrocyte progenitors promotes remyelination

    PubMed Central

    Wegener, Amélie; Deboux, Cyrille; Bachelin, Corinne; Frah, Magali; Kerninon, Christophe; Seilhean, Danielle; Weider, Matthias; Wegner, Michael

    2015-01-01

    The basic helix-loop-helix transcription factor Olig2 is a key determinant for the specification of neural precursor cells into oligodendrocyte progenitor cells. However, the functional role of Olig2 in oligodendrocyte migration and differentiation remains elusive both during developmental myelination and under demyelinating conditions of the adult central nervous system. To decipher Olig2 functions, we generated transgenic mice (TetOlig2:Sox10rtTA/+) overexpressing Olig2 in Sox10+ oligodendroglial cells in a doxycycline inducible manner. We show that Olig2 overexpression increases the generation of differentiated oligodendrocytes, leading to precocious myelination of the central nervous system. Unexpectedly, we found that gain of Olig2 function in oligodendrocyte progenitor cells enhances their migration rate. To determine whether Olig2 overexpression in adult oligodendrocyte progenitor cells promotes oligodendrocyte regeneration for myelin repair, we induced lysophosphatidylcholine demyelination in the corpus callosum of TetOlig2:Sox10rtTA/+ and control mice. We found that Olig2 overexpression enhanced oligodendrocyte progenitor cell differentiation and remyelination. To assess the relevance of these findings in demyelinating diseases, we also examined OLIG2 expression in multiple sclerosis lesions. We demonstrate that OLIG2 displays a differential expression pattern in multiple sclerosis lesions that correlates with lesion activity. Strikingly, OLIG2 was predominantly detected in NOGO-A+ (now known as RTN4-A) maturing oligodendrocytes, which prevailed in active lesion borders, rather than chronic silent and shadow plaques. Taken together, our data provide proof of principle indicating that OLIG2 overexpression in oligodendrocyte progenitor cells might be a possible therapeutic mechanism for enhancing myelin repair. PMID:25564492

  1. [Stem and progenitor cells in biostructure of blood vessel walls].

    PubMed

    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  2. Observations of Core-Collapse Supernovae with Candidate Progenitor Identifications.

    NASA Astrophysics Data System (ADS)

    Elias-Rosa, Nancy; van Dyk, Schuyler D.

    2010-02-01

    Supernovae (SNe) have a profound effect on galaxies. They are clearly very important events deserving of intense study. Yet, even with nearly 4000 historical SNe, we know relatively little about the stars which give rise to these powerful explosions. The main limitation has been the lack of spatial resolution in pre-SN imaging data. However, since 1999 our team has been at the vanguard of directly identifying the progenitor stars of Core-Collapse (CC-) SNe in Hubble Space Telescope (HST) images. From this exciting new line of study, the emerging trend from a growing number of detections for Type II-Plateau SNe is that their progenitors appear to be relatively low mass (8-20 M_⊙) red supergiants, although more cases are needed. The nature of the progenitors of Type Ib/c SNe, a subset of which are associated with the amazing gamma-ray bursts, remains ambiguous. In HST Cycle 17 we are expecting to trigger our ToO observations using ACS/HRC (GO-11575) on 4 nearby (within 17 Mpc) CC-SNe, to determine the identities of the progenitors. It is conceivable that at least half of these will be discovered in the southern hemisphere. To fully characterize the progenitor star, we require detailed light curves and spectral evolution for the SNe, starting soon after discovery, to estimate the reddening to the SNe, characterize the overall luminosity and obtain a better understanding of the physics of the event. Therefore, to support the HST work, we are requesting up to 2 ToO triggers during semester 2010A, where we will monitor the SNe in BVRI with ANDICAM, and the 300 l/mm grating with the Goodman.

  3. Effect of Reishi polysaccharides on human stem/progenitor cells.

    PubMed

    Chen, Wan-Yu; Yang, Wen-Bin; Wong, Chi-Huey; Shih, Daniel Tzu-Bi

    2010-12-15

    The polysaccharide fraction of Ganoderma lucidum (F3) was found to benefit our health in many ways by influencing the activity of tissue stem/progenitor cells. In this study, F3 was found to promote the adipose tissue MSCs' aggregation and chondrosphere formation, with the increase of CAM (N-CAM, I-CAM) expressions and autokine (BMP-2, IL-11, and aggrecan) secretions, in an in vitro chondrogenesis assay. In a stem cell expansion culture, it possesses the thrombopoietin (TPO) and GM-CSF like functions to enhance the survival/renewal abilities of primitive hematopoietic stem/progenitor cells (HSCs). F3 was found to promote the dendrite growth of blood mononuclear cells (MNCs) and the expression of cell adhesion molecules in the formation of immature dendritic cells (DC). On the other hand, F3 exhibited inhibitory effects on blood endothelial progenitor (EPC) colony formation, with concomitant reduction of cell surface endoglin (CD105) and vascular endothelial growth factor receptor-3 (VEGFR-3) marker expressions, in the presence of angiogenic factors. A further cytokine array analysis revealed that F3 indeed inhibited the angiogenin synthesis and enhanced IL-1, MCP-1, MIP-1, RANTES, and GRO productions in the blood EPC derivation culture. Collectively, we have demonstrated that the polysaccharide fraction of G. lucidum F3 exhibits cytokine and chemokine like functions which are beneficial to human tissue stem/progenitor cells by modulating their CAM expressions and biological activities. These findings provide us a better the observation that F3 glycopolysaccharides indeed possesses anti-angiogenic and immune-modulating functions and promotes hematopoietic stem/progenitor cell homing for better human tissue protection, reducing disease progression and health.

  4. Fas transduces dual apoptotic and trophic signals in hematopoietic progenitors.

    PubMed

    Pearl-Yafe, Michal; Stein, Jerry; Yolcu, Esma S; Farkas, Daniel L; Shirwan, Haval; Yaniv, Isaac; Askenasy, Nadir

    2007-12-01

    Stem cells and progenitors are often required to realize their differentiation potential in hostile microenvironments. The Fas/Fas ligand (FasL) interaction is a major effector pathway of apoptosis, which negatively regulates the expansion of differentiated hematopoietic cells. The involvement of this molecular interaction in the function of hematopoietic stem and progenitor cells is not well understood. In the murine syngeneic transplant setting, both Fas and FasL are acutely upregulated in bone marrow-homed donor cells; however, the Fas(+) cells are largely insensitive to FasL-induced apoptosis. In heterogeneous populations of lineage-negative (lin(-)) bone marrow cells and progenitors isolated by counterflow centrifugal elutriation, trimerization of the Fas receptor enhanced the clonogenic activity. Inhibition of caspases 3 and 8 did not affect the trophic signals mediated by Fas, yet it efficiently blocked the apoptotic pathways. Fas-mediated tropism appears to be of physiological significance, as pre-exposure of donor cells to FasL improved the radioprotective qualities of hematopoietic progenitors, resulting in superior survival of myeloablated hosts. Under these conditions, the activity of long-term reconstituting cells was not affected, as determined in sequential secondary and tertiary transplants. Dual caspase-independent tropic and caspase-dependent apoptotic signaling place the Fas receptor at an important junction of activation and death. This regulatory mechanism of hematopoietic homeostasis activates progenitors to promote the recovery from aplasia and converts into a negative regulator in distal stages of cell differentiation. Disclosure of potential conflicts of interest is found at the end of this article.

  5. Characterization of progenitor domains in the developing mouse thalamus.

    PubMed

    Vue, Tou Yia; Aaker, Joshua; Taniguchi, Aya; Kazemzadeh, Christina; Skidmore, Jennifer M; Martin, Donna M; Martin, James F; Treier, Mathias; Nakagawa, Yasushi

    2007-11-01

    To understand the molecular basis of the specification of thalamic nuclei, we analyzed the expression patterns of various transcription factors and defined progenitor cell populations in the embryonic mouse thalamus. We show that the basic helix-loop-helix (bHLH) transcription factor Olig3 is expressed in the entire thalamic ventricular zone and the zona limitans intrathalamica (ZLI). Next, we define two distinct progenitor domains within the thalamus, which we name pTH-R and pTH-C, located caudal to the ZLI. pTH-R is immediately caudal to the ZLI and expresses Nkx2.2, Mash1, and Olig3. pTH-C is caudal to pTH-R and expresses Ngn1, Ngn2, and Olig3. Short-term lineage analysis of Olig3-, Mash1-, Ngn1-, and Ngn2-expressing progenitor cells as well as tracing the Pitx2 cell lineage suggests that pTH-C is the only major source of thalamic nuclei containing neurons that project to the cerebral cortex, whereas pTH-R and ZLI are likely to produce distinct postmitotic populations outside of the cortex-projecting part of the thalamus. To determine if pTH-C is composed of subdomains, we characterized expression of the homeodomain protein Dbx1 and the bHLH protein Olig2. We show that Dbx1 is expressed in caudodorsal-high to rostroventral-low gradient within pTH-C. Analysis of heterozygous Dbx1(nlslacZ) knockin mice demonstrated that Dbx1-expressing progenitors preferentially give rise to caudodorsal thalamic nuclei. Olig2 is expressed in an opposite gradient within pTH-C to that of Dbx1. These results establish the molecular heterogeneity within the progenitor cells of the thalamus, and suggest that such heterogeneity contributes to the specification of thalamic nuclei.

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

    PubMed

    Yang, Yi; Xu, Jie; Chen, Huo; Fei, Xia; Tang, YuXu; Yan, Yunqiu; Zhang, Huimin; Zhang, Jinping

    2016-04-05

    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.

  7. 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

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

    PubMed

    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

    2015-03-23

    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.

  9. Playing Well with Others: Extrinsic Cues Regulate Neural Progenitor Temporal Identity to Generate Neuronal Diversity.

    PubMed

    Syed, Mubarak Hussain; Mark, Brandon; Doe, Chris Q

    2017-09-09

    During neurogenesis, vertebrate and Drosophila progenitors change over time as they generate a diverse population of neurons and glia. Vertebrate neural progenitors have long been known to use both progenitor-intrinsic and progenitor-extrinsic cues to regulate temporal patterning. In contrast, virtually all temporal patterning mechanisms discovered in Drosophila neural progenitors (neuroblasts) involve progenitor-intrinsic temporal transcription factor cascades. Recent results, however, have revealed several extrinsic pathways that regulate Drosophila neuroblast temporal patterning: nutritional cues regulate the timing of neuroblast proliferation/quiescence and a steroid hormone cue that is required for temporal transcription factor expression. Here, we discuss newly discovered extrinsic cues regulating neural progenitor temporal identity in Drosophila, highlight conserved mechanisms, and raise open questions for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. PROGENITOR-EXPLOSION CONNECTION AND REMNANT BIRTH MASSES FOR NEUTRINO-DRIVEN SUPERNOVAE OF IRON-CORE PROGENITORS

    SciTech Connect

    Ugliano, Marcella; Janka, Hans-Thomas; Marek, Andreas; Arcones, Almudena

    2012-09-20

    We perform hydrodynamic supernova (SN) simulations in spherical symmetry for over 100 single stars of solar metallicity to explore the progenitor-explosion and progenitor-remnant connections established by the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen such that explosion energy, nickel production, and energy release by the compact remnant of progenitors around 20 M{sub Sun} are compatible with SN 1987A. Thus, we are able to simulate the accretion phase, initiation of the explosion, subsequent neutrino-driven wind phase for 15-20 s, and the further evolution of the blast wave for hours to days until fallback is completed. Our results challenge long-standing paradigms. We find that remnant mass, launch time, and properties of the explosion depend strongly on the stellar structure and exhibit large variability even in narrow intervals of the progenitors' zero-age main-sequence mass. While all progenitors with masses below {approx}15 M{sub Sun} yield NSs, black hole (BH) as well as NS formation is possible for more massive stars, where partial loss of the hydrogen envelope leads to weak reverse shocks and weak fallback. Our NS baryonic masses of {approx}1.2-2.0 M{sub Sun} and BH masses >6 M{sub Sun} are compatible with a possible lack of low-mass BHs in the empirical distribution. Neutrino heating accounts for SN energies between some 10{sup 50} erg and {approx}2 Multiplication-Sign 10{sup 51} erg but can hardly explain more energetic explosions and nickel masses higher than 0.1-0.2 M{sub Sun }. These seem to require an alternative SN mechanism.

  11. Endothelial progenitor cells: Exploring the pleiotropic effects of statins.

    PubMed

    Sandhu, Kully; Mamas, Mamas; Butler, Robert

    2017-01-26

    Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction, prior to any significant change in lipid profile. Therefore, pleiotropic mechanisms, other than lowering lipid profile alone, must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell (EPC) identification, role in vascular repair, factors affecting EPC numbers, the role of statins in current medical practice and their effects on EPC number.

  12. Endothelial progenitor cells: Exploring the pleiotropic effects of statins

    PubMed Central

    Sandhu, Kully; Mamas, Mamas; Butler, Robert

    2017-01-01

    Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction, prior to any significant change in lipid profile. Therefore, pleiotropic mechanisms, other than lowering lipid profile alone, must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell (EPC) identification, role in vascular repair, factors affecting EPC numbers, the role of statins in current medical practice and their effects on EPC number. PMID:28163831

  13. Imparting regenerative capacity to limbs by progenitor cell transplantation

    PubMed Central

    Lin, Gufa; Chen, Ying; Slack, Jonathan M.W.

    2012-01-01

    Summary The frog Xenopus can normally regenerate its limbs at early developmental stages but loses the ability during metamorphosis. This behavior provides a potential gain-of-function model for measures that can enhance limb regeneration. Here we show that frog limbs can be caused to form multidigit regenerates after receiving transplants of larval limb progenitor cells. It is necessary to activate Wnt/β -catenin signaling in the cells, and to add Sonic hedgehog, FGF10 and thymosin β4. These factors promote survival and growth of the grafted cells and also provide pattern information. The eventual regenerates are not composed solely of donor tissue; the host cells also make a substantial contribution despite their lack of regeneration-competence. Cells from adult frog legs or from regenerating tadpole tails do not promote limb regeneration, demonstrating the necessity for limb progenitor cells. These findings have obvious implications for the development of a technology to promote limb regeneration in mammals. PMID:23273877

  14. 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

  15. Clinical Application of Endothelial Progenitor Cell: Are We Ready?

    PubMed Central

    Wang, Chao-Hung; Huang, Po-Hsun; Chen, Jaw-Wen; Lin, Shing-Jong; Lee, Ming-Feng; Yang, Ning-I; Cherng, Wen-Jin

    2013-01-01

    The discovery of circulating endothelial progenitor cells (EPCs) opened up a new era of EPC-based therapies for cardiovascular diseases. While researchers are enthusiastic about applying EPCs to clinical therapy, progress has been substantially limited due to the lack of a thorough characterization and understanding of early and late outgrowth EPCs (also called endothelial colony-forming cell, ECFCs) biology. As a means of facilitating the understanding of how late EPCs can most effectively be applied to clinical therapeutics, this article reviews the recent progress covering 5 important issues: (1) The best passages of ex vivo-cultivated EPCs for cell therapy; (2) inflammatory activation of late EPCs: a real world consideration; (3) late EPC is not an endothelial cell: an issue of cell contamination; (4) ways to improve EPC function and differentiation; and (5) how to separate and delete smooth muscle progenitor cells (SPCs). PMID:27122748

  16. 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.

  17. Is black-hole ringdown a memory of its progenitor?

    PubMed

    Kamaretsos, Ioannis; Hannam, Mark; Sathyaprakash, B S

    2012-10-05

    We perform an extensive numerical study of coalescing black-hole binaries to understand the gravitational-wave spectrum of quasinormal modes excited in the merged black hole. Remarkably, we find that the masses and spins of the progenitor are clearly encoded in the mode spectrum of the ringdown signal. Some of the mode amplitudes carry the signature of the binary's mass ratio, while others depend critically on the spins. Simulations of precessing binaries suggest that our results carry over to generic systems. Using Bayesian inference, we demonstrate that it is possible to accurately measure the mass ratio and a proper combination of spins even when the binary is itself invisible to a detector. Using a mapping of the binary masses and spins to the final black-hole spin allows us to further extract the spin components of the progenitor. Our results could have tremendous implications for gravitational astronomy by facilitating novel tests of general relativity using merging black holes.

  18. 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

  19. Renal progenitors: Roles in kidney disease and regeneration

    PubMed Central

    Chambers, Brooke E; Wingert, Rebecca A

    2016-01-01

    Kidney disease is a devastating condition that affects millions of people worldwide, and its prevalence is predicted to significantly increase. The kidney is a complex organ encompassing many diverse cell types organized in a elaborate tissue architecture, making regeneration a challenging feat. In recent years, there has been a surge in the field of stem cell research to develop regenerative therapies for various organ systems. Here, we review some recent progressions in characterizing the role of renal progenitors in development, regeneration, and kidney disease in mammals. We also discuss how the zebrafish provides a unique experimental animal model that can provide a greater molecular and genetic understanding of renal progenitors, which may contribute to the development of potential regenerative therapies for human renal afflictions. PMID:27928463

  20. 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.

  1. Pax genes: regulators of lineage specification and progenitor cell maintenance.

    PubMed

    Blake, Judith A; Ziman, Melanie R

    2014-02-01

    Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We also discuss mechanistic insights into the roles of Pax genes in regeneration and in adult diseases, including cancer.

  2. Fate mapping by piggyBac transposase reveals that neocortical GLAST+ progenitors generate more astrocytes than Nestin+ progenitors in rat neocortex.

    PubMed

    Siddiqi, Faez; Chen, Fuyi; Aron, Abraham W; Fiondella, Christopher G; Patel, Komal; LoTurco, Joseph J

    2014-02-01

    Progenitors within the neocortical ventricular zone (VZ) first generate pyramidal neurons and then astrocytes. We applied novel piggyBac transposase lineage tracking methods to fate-map progenitor populations positive for Nestin or glutamate and aspartate transpoter (GLAST) promoter activities in the rat neocortex. GLAST+ and Nestin+ progenitors at embryonic day 13 (E13) produce lineages containing similar rations of neurons and astrocytes. By E15, the GLAST+ progenitor population diverges significantly to produce lineages with 5-10-fold more astrocytes relative to neurons than generated by the Nestin+ population. To determine when birth-dated progeny within GLAST+ and Nestin+ populations diverge, we used a Cre/loxP fate-mapping system in which plasmids are lost after a cell division. By E18, birth-dated progeny of GLAST+ progenitors give rise to 2-3-fold more neocortical astrocytes than do Nestin+ progenitors. Finally, we used a multicolor clonal labeling method to show that the GLAST+ population labeled at E15 generates astrocyte progenitors that produce larger, spatially restricted, clonal clusters than the Nestin+ population. This study provides in vivo evidence that by mid-corticogenesis (E15), VZ progenitor populations have significantly diversified in terms of their potential to generate astrocytes and neurons.

  3. Does energy of type IIP supernovae depend on progenitor mass?

    NASA Astrophysics Data System (ADS)

    Chugai, Nikolai

    The oxygen [O I] 6300 A emission doublet, seen in nebular spectra of core-collapse supernovae, is used to obtain oxygen density in central zone of a sample of SN IIP. The inferred values of the oxygen density on day 300 turn out to fall into rather narrow range. This result does not depend on the distance, extinction, or model assumptions. The found density distribution led us to conclude that the SN IIP explosion energy monotonically increases with the progenitor mass.

  4. Regulation of Circulating Progenitor Cells in Left Ventricular Dysfunction

    PubMed Central

    Boilson, Barry A.; Larsen, Katarina; Harbuzariu, Adriana; Delacroix, Sinny; Korinek, Josef; Froehlich, Harald; Bailey, Kent R.; Scott, Christopher G.; Shapiro, Brian P.; Boerrigter, Guido; Chen, Horng H.; Redfield, Margaret M.; Burnett, John C.; Simari, Robert D.

    2011-01-01

    Background Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. Methods and Results A pacing model of severe LV dysfunction and a hypertensive renal wrap (RW) model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs:CD34+/CD45dim/VEGFR2-) and endothelial progenitor cells (EPCs:CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45 dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman Rank correlation = -0.67, p=0.03). In the RW model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. Conclusions This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells leading to their reduced survival and decline in numbers. PMID:20573992

  5. Endothelial progenitor cells, cardiovascular risk factors and lifestyle modifications.

    PubMed

    Di Stefano, Rossella; Felice, Francesca; Feriani, Roberto; Balbarini, Alberto

    2013-04-01

    Endothelial progenitor cells (EPCs) contribute substantially to preservation of a structurally and functionally intact endothelium. EPCs home in to the sites of endothelial injury and ischemia, where they proliferate, differentiate and integrate into the endothelial layer or exert a paracrine function by producing vascular growth factors. This review will focus on successful lifestyle interventions that aim to maintain vascular health through beneficial actions on cell populations with vasculogenic potential. The results of the studies proving the role of healthy lifestyle are particularly emphasized.

  6. Engineering Retina from Human Retinal Progenitors (Cell Lines)

    PubMed Central

    Cao, Yang

    2009-01-01

    Retinal degeneration resulting in the loss of photoreceptors is the leading cause of blindness. Several therapeutic protocols are under consideration for treatment of this disease. Tissue replacement is one such strategy currently being explored. However, availability of tissues for transplant poses a major obstacle. Another strategy with great potential is the use of adult stem cells, which could be expanded in culture and then utilized to engineer retinal tissue. In this study, we have explored a spontaneously immortalized human retinal progenitor cell line for its potential in retinal engineering using rotary cultures to generate three-dimensional (3D) structures. Retinal progenitors cultured alone or cocultured with retinal pigment epithelial cells form aggregates. The aggregate size increases between days 1 and 10. The cells grown as a 3D culture rotary system, which promotes cell–cell interaction, retain a spectrum of differentiation capability. Photoreceptor differentiation in these cultures is confirmed by significant upregulation of rhodopsin and AaNat, an enzyme implicated in melatonin synthesis (immunohistochemistry and Western blot analysis). Photoreceptor induction and differentiation is further attested to by the upregulation of rod transcription factor Nrl, Nr2e3, expression of interstitial retinal binding protein, and rhodopsin kinase by reverse transcription–polymerase chain reaction. Differentiation toward other cell lineages is confirmed by the expression of tyrosine hydroxylase in amacrine cells, thy 1.1 expression in ganglion cells and calbindin, and GNB3 expression in cone cells. The capability of retinal progenitors to give rise to several retinal cell types when grown as aggregated cells in rotary culture offers hope that progenitor stem cells under appropriate culture conditions will be valuable to engineer retinal constructs, which could be further tested for their transplant potential. The fidelity with which this multipotential cell

  7. Extracellular Matrix-Mediated Differentiation of Periodontal Progenitor Cells

    PubMed Central

    Dangaria, Smit J.; Ito, Yoshihiro; Walker, Cameron; Druzinsky, Robert; Luan, Xianghong; Diekwisch, Thomas G.H.

    2009-01-01

    The periodontal ligament (PDL) is a specialized connective tissue that connects the surface of the tooth root with the bony tooth socket. The healthy PDL harbors stem cell niches and extracellular matrix (ECM) microenvironments that facilitate periodontal regeneration. During periodontal disease, the PDL is often compromised or destroyed, reducing the life-span of the tooth. In order to explore new approaches toward the regeneration of diseased periodontal tissues, we have tested the effect of periodontal ECM signals, fibroblast growth factor 2 (FGF2), connective tissue growth factor (CTGF), and the cell adhesion peptide Arg-Gly- Asp (RGD) on the differentiation of two types of periodontal progenitor cells, PDL progenitor cells (PDLPs) and dental follicle progenitor cells (DFCs). Our studies documented that CTGF and FGF2 significantly enhanced the expression of collagens I & III, biglycan and periostin in tissue engineered regenerates after 4 weeks compared to untreated controls. Specifically, CTGF promoted mature PDL-like tissue regeneration as demonstrated by dense periostin localization in collagen fiber bundles. CTGF and FGF2 displayed synergistic effects on collagen III and biglycan gene expression, while effects on mineralization were antagonistic to each other: CTGF promoted while FGF2 inhibited mineralization in PDL cell cultures. Incorporation of RGD peptides in hydrogel matrices significantly enhanced attachment, spreading, survival and mineralization of the encapsulated DFCs, suggesting that RGD additives might promote the use of hydrogels for periodontal mineralized tissue engineering. Together, our studies have documented the effect of three key components of the periodontal ECM on the differentiation of periodontal progenitor populations. PMID:19433344

  8. Characterization of Botulinum Progenitor Toxins by Mass Spectrometry

    DTIC Science & Technology

    2005-08-01

    strains Hall, Okra , Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with...sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra , Stockholm, MDPH, Alaska, Langeland, and 89 representing...from sero- types A (strain 62A), B (strain Okra ), C (003-9), D (CB-16), E (no designation; equivalent to NCTC 11219 by analysis), and F (Langeland) that

  9. Homing and migration assays of hematopoietic stem/progenitor cells.

    PubMed

    He, Xi C; Li, Zhenrui; Sugimura, Rio; Ross, Jason; Zhao, Meng; Li, Linheng

    2014-01-01

    Hematopoietic stem and progenitor cells (HSPCs) reside mainly in bone marrow; however, under homeostatic and stressed conditions, HSPCs dynamically change their location-either egressing from bone marrow and getting into circulation, a process of mobilization; or coming back to the bone marrow, the homing process. How to analyze these two processes will be critical for understanding the behavior of HSPCs. Here we provide an experimental protocol to monitor and analyze homing and migration of HSPCs.

  10. 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

  11. Circulating endothelial progenitor cells in obese children and adolescents.

    PubMed

    Pires, António; Martins, Paula; Paiva, Artur; Pereira, Ana Margarida; Marques, Margarida; Castela, Eduardo; Sena, Cristina; Seiça, Raquel

    2015-01-01

    This study aimed to investigate the relationship between circulating endothelial progenitor cell count and endothelial activation in a pediatric population with obesity. Observational and transversal study, including 120 children and adolescents with primary obesity of both sexes, aged 6-17 years, who were recruited at this Cardiovascular Risk Clinic. The control group was made up of 41 children and adolescents with normal body mass index. The variables analyzed were: age, gender, body mass index, systolic and diastolic blood pressure, high-sensitivity C-reactive protein, lipid profile, leptin, adiponectin, homeostasis model assessment-insulin resistance, monocyte chemoattractant protein-1, E-selectin, asymmetric dimethylarginine and circulating progenitor endothelial cell count. Insulin resistance was correlated to asymmetric dimethylarginine (ρ=0.340; p=0.003), which was directly, but weakly correlated to E-selectin (ρ=0.252; p=0.046). High sensitivity C-reactive protein was not found to be correlated to markers of endothelial activation. Systolic blood pressure was directly correlated to body mass index (ρ=0.471; p<0.001) and the homeostasis model assessment-insulin resistance (ρ=0.230; p=0.012), and inversely correlated to adiponectin (ρ=-0.331; p<0.001) and high-density lipoprotein cholesterol (ρ=-0.319; p<0.001). Circulating endothelial progenitor cell count was directly, but weakly correlated, to body mass index (r=0.211; p=0.016), leptin (ρ=0.245; p=0.006), triglyceride levels (r=0.241; p=0.031), and E-selectin (ρ=0.297; p=0.004). Circulating endothelial progenitor cell count is elevated in obese children and adolescents with evidence of endothelial activation, suggesting that, during infancy, endothelial repairing mechanisms are present in the context of endothelial activation. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  12. 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).

  13. Mouse Mesenchymal Progenitor Cells Expressing Adipogenic and Osteogenic Transcription Factors Suppress the Macrophage Inflammatory Response.

    PubMed

    Fernandez, Natalie; Renna, Heather; McHugh, Lauren; Mazolkova, Katie; Crugnola, William; Evans, Jodi F

    2017-01-01

    Mesenchymal progenitor cell characteristics that can identify progenitor populations with specific functions in immunity are actively being investigated. Progenitors from bone marrow and adipose tissue regulate the macrophage (MΦ) inflammatory response by promoting the switch from an inflammatory to an anti-inflammatory phenotype. Conversely, mesenchymal progenitors from the mouse aorta (mAo) support and contribute to the MΦ response under inflammatory conditions. We used cell lines with purported opposing immune-regulatory function, a bone marrow derived mesenchymal progenitor cell line (D1) and a mouse aorta derived mesenchymal progenitor cell line (mAo). Their interaction and regulation of the MΦ cell response to the inflammatory mediator, lipopolysaccharide (LPS), was examined by coculture. As expected, D1 cells suppressed NO, TNF-α, and IL-12p70 production but MΦ phagocytic activity remained unchanged. The mAo cells enhanced NO and TNF-α production in coculture and enhanced MΦ phagocytic activity. Using flow cytometry and PCR array, we then sought to identify sets of MSC-associated genes and markers that are expressed by these progenitor populations. We have determined that immune-supportive mesenchymal progenitors highly express chondrogenic and tenogenic transcription factors while immunosuppressive mesenchymal progenitors highly express adipogenic and osteogenic transcription factors. These data will be useful for the isolation, purification, and modification of mesenchymal progenitors to be used in the treatment of inflammatory diseases.

  14. Mouse Mesenchymal Progenitor Cells Expressing Adipogenic and Osteogenic Transcription Factors Suppress the Macrophage Inflammatory Response

    PubMed Central

    Fernandez, Natalie; Renna, Heather; McHugh, Lauren; Mazolkova, Katie; Crugnola, William

    2017-01-01

    Mesenchymal progenitor cell characteristics that can identify progenitor populations with specific functions in immunity are actively being investigated. Progenitors from bone marrow and adipose tissue regulate the macrophage (MΦ) inflammatory response by promoting the switch from an inflammatory to an anti-inflammatory phenotype. Conversely, mesenchymal progenitors from the mouse aorta (mAo) support and contribute to the MΦ response under inflammatory conditions. We used cell lines with purported opposing immune-regulatory function, a bone marrow derived mesenchymal progenitor cell line (D1) and a mouse aorta derived mesenchymal progenitor cell line (mAo). Their interaction and regulation of the MΦ cell response to the inflammatory mediator, lipopolysaccharide (LPS), was examined by coculture. As expected, D1 cells suppressed NO, TNF-α, and IL-12p70 production but MΦ phagocytic activity remained unchanged. The mAo cells enhanced NO and TNF-α production in coculture and enhanced MΦ phagocytic activity. Using flow cytometry and PCR array, we then sought to identify sets of MSC-associated genes and markers that are expressed by these progenitor populations. We have determined that immune-supportive mesenchymal progenitors highly express chondrogenic and tenogenic transcription factors while immunosuppressive mesenchymal progenitors highly express adipogenic and osteogenic transcription factors. These data will be useful for the isolation, purification, and modification of mesenchymal progenitors to be used in the treatment of inflammatory diseases. PMID:28191017

  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 Central

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

    2015-01-01

    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. Obesity, proinflammatory mediators, adipose tissue progenitors, and breast cancer.

    PubMed

    Bertolini, Francesco; Orecchioni, Stefania; Petit, Jean-Yves; Kolonin, Mikhail G

    2014-11-01

    There is emerging evidence that obesity is associated with an increase in the incidence, severity, and mortality from different types of cancer, including postmenopausal breast cancer. Here, we discuss the role of white adipose tissue (WAT) cells and of related soluble factors in the local and metastatic growth of this neoplastic disease. Moreover, we discuss the recent increase in the use of WAT-derived progenitor cells in breast cancer patients to enhance the quality of breast reconstruction and the related risks. In several murine models, WAT cells and progenitors were found to have cooperative roles in promoting local breast cancer. Moreover, they were found to contribute to adipocytes and pericytes supporting the cancer vasculature, and stimulated the metastatic progression of breast cancer. There are some clinically retrospective data showing a significant increase in the frequency of intraepithelial neoplasia in patients who received a lipofilling procedure for breast reconstruction compared with controls. Preclinical models and clinical studies are urgently needed to investigate how to inhibit the tumor-promoting activity of WAT cells and progenitors. The risks associated with the use of WAT cells for breast reconstructions should be better investigated retrospectively and prospectively.

  18. Irx4 Marks a Multipotent, Ventricular-Specific Progenitor Cell.

    PubMed

    Nelson, Daryl O; Lalit, Pratik A; Biermann, Mitch; Markandeya, Yogananda S; Capes, Deborah L; Addesso, Luke; Patel, Gina; Han, Tianxiao; John, Manorama C; Powers, Patricia A; Downs, Karen M; Kamp, Timothy J; Lyons, Gary E

    2016-12-01

    While much progress has been made in the resolution of the cellular hierarchy underlying cardiogenesis, our understanding of chamber-specific myocardium differentiation remains incomplete. To better understand ventricular myocardium differentiation, we targeted the ventricle-specific gene, Irx4, in mouse embryonic stem cells to generate a reporter cell line. Using an antibiotic-selection approach, we purified Irx4(+) cells in vitro from differentiating embryoid bodies. The isolated Irx4(+) cells proved to be highly proliferative and presented Cxcr4, Pdgfr-alpha, Flk1, and Flt1 on the cell surface. Single Irx4(+) ventricular progenitor cells (VPCs) exhibited cardiovascular potency, generating endothelial cells, smooth muscle cells, and ventricular myocytes in vitro. The ventricular specificity of the Irx4(+) population was further demonstrated in vivo as VPCs injected into the cardiac crescent subsequently produced Mlc2v(+) myocytes that exclusively contributed to the nascent ventricle at E9.5. These findings support the existence of a newly identified ventricular myocardial progenitor. This is the first report of a multipotent cardiac progenitor that contributes progeny specific to the ventricular myocardium. Stem Cells 2016;34:2875-2888. © 2016 AlphaMed Press.

  19. Stem and progenitor cells: advancing bone tissue engineering.

    PubMed

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  20. 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.

  1. In Search of Adrenocortical Stem and Progenitor Cells

    PubMed Central

    Kim, Alex C.; Barlaskar, Ferdous M.; Heaton, Joanne H.; Else, Tobias; Kelly, Victoria R.; Krill, Kenneth T.; Scheys, Joshua O.; Simon, Derek P.; Trovato, Alessia; Yang, Wei-Hsiung; Hammer, Gary D.

    2009-01-01

    Scientists have long hypothesized the existence of tissue-specific (somatic) stem cells and have searched for their location in different organs. The theory that adrenocortical organ homeostasis is maintained by undifferentiated stem or progenitor cells can be traced back nearly a century. Similar to other organ systems, it is widely believed that these rare cells of the adrenal cortex remain relatively undifferentiated and quiescent until needed to replenish the organ, at which time they undergo proliferation and terminal differentiation. Historical studies examining cell cycle activation by label retention assays and regenerative potential by organ transplantation experiments suggested that the adrenocortical progenitors reside in the outer periphery of the adrenal gland. Over the past decade, the Hammer laboratory, building on this hypothesis and these observations, has endeavored to understand the mechanisms of adrenocortical development and organ maintenance. In this review, we summarize the current knowledge of adrenal organogenesis. We present evidence for the existence and location of adrenocortical stem/progenitor cells and their potential contribution to adrenocortical carcinomas. Data described herein come primarily from studies conducted in the Hammer laboratory with incorporation of important related studies from other investigators. Together, the work provides a framework for the emerging somatic stem cell field as it relates to the adrenal gland. PMID:19403887

  2. 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

  3. 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

  4. Identifying Supernova Progenitors and Constraining the Explosion Channels

    NASA Astrophysics Data System (ADS)

    Van Dyk, Schuyler D.

    2012-09-01

    Connecting the endpoints of massive star evolution with the various types of core-collapse supernovae (SNe) is ultimately the fundamental puzzle to be explored and solved. We can assemble clues indirectly, e.g., from information about the environments in which stars explode and establish constraints on the evolutionary phases of these stars. However, this is best accomplished through direct identification of the actual star that has exploded in pre-supernova imaging, preferably in more than one photometric band, where color and luminosity for the star can be precisely measured. We can then interpret the star's properties in light of expectations from the latest massive stellar evolutionary models, to attempt to assign an initial mass to the progenitor. So far, this has been done most successfully for SNe II-P, for which we now know that red supergiants in a relatively limited initial mass range are responsible. More recently, we have limited examples of the progenitors of SNe II-L, IIn, and IIb. The progenitors of SNe Ib and Ic, however, have been elusive so far; I will discuss the current status of our knowledge of this particular channel.

  5. NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells

    PubMed Central

    Masters, Seth L.; Gerlic, Motti; Metcalf, Donald; Preston, Simon; Pellegrini, Marc; O’Donnell, Joanne A.; McArthur, Kate; Baldwin, Tracey M.; Chevrier, Stephane; Nowell, Cameron J.; Cengia, Louise H.; Henley, Katya J.; Collinge, Janelle E.; Kastner, Daniel L.; Feigenbaum, Lionel; Hilton, Douglas J.; Alexander, Warren S.; Kile, Benjamin T.; Croker, Ben A.

    2014-01-01

    Cytopenias are key prognostic indicators of life-threatening infection, contributing to immunosuppression and mortality. Here we define a role for Caspase-1-dependent death, known as pyroptosis, in infection-induced cytopenias by studying inflammasome activation in hematopoietic progenitor cells. The NLRP1a inflammasome is expressed in hematopoietic progenitor cells and its activation triggers their pyroptotic death. Active NLRP1a induced a lethal systemic inflammatory disease that was driven by Caspase-1 and IL-1β but was independent of apoptosis-associated speck-like protein containing a CARD (ASC) and ameliorated by IL-18. Surprisingly, in the absence of IL-1β-driven inflammation, active NLRP1a triggered pyroptosis of hematopoietic progenitor cells resulting in leukopenia in the steady state. During periods of hematopoietic stress induced by chemotherapy or lymphocytic choriomeningitis virus (LCMV) infection, active NLRP1a caused prolonged cytopenia, bone marrow hypoplasia and immunosuppression. Conversely, NLRP1-deficient mice showed enhanced recovery from chemotherapy and LCMV infection, demonstrating that NLRP1 acts as a cellular sentinel to alert Caspase-1 to hematopoietic and infectious stress. PMID:23219391

  6. 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.

  7. ENDOTHELIAL PROGENITOR CELLS AS SHUTTLE OF ANTICANCER AGENTS.

    PubMed

    Laurenzana, Anna; Margheri, Francesca; Chilla', Anastasia; Biagioni, Alessio; Margheri, Giancarlo; Calorini, Lido; Fibbi, Gabriella; Del Rosso, Mario

    2016-08-08

    Cell therapies are treatments in which stem or progenitor cells are induced to differentiate into the specific cell type required to repair damaged or destroyed tissues. Following their discovery, endothelial progenitor cells (EPCs) have stimulated a worldwide interest as possible vehicles to perform an autologous cell-therapy of tumors. Taking into account the tumor-homing properties of EPCs, two different approaches to control cancer progression have been pursued by combining the cell-based therapy with gene therapy or with nanomedicine. The first one is based on the possibility to engineer EPCs to express different transgenes, the second one on the capacity of EPCs to uptake nanomaterials. Here we will review the most important progresses covering the following issues: the characterization of bona fide endothelial progenitor cells, their role in tumor vascularisation and metastasis, and preclinical data about their use in cell-based tumor therapy, considering anti-angiogenic, suicide, immune-stimulating and oncolytic virus gene-therapy. The mixed approach of EPC cell therapy and nanomedicine will be discussed in terms of plasmonic-dependent thermoablation and molecular imaging.

  8. Multipotent adult progenitor cells improve the hematopoietic function in myelodysplasia.

    PubMed

    Roobrouck, Valerie D; Wolfs, Esther; Delforge, Michel; Broekaert, Dorien; Chakraborty, Soumen; Sels, Kathleen; Vanwelden, Thomas; Holvoet, Bryan; Lhoest, Larissa; Khurana, Satish; Pandey, Shubham; Hoornaert, Chloé; Ponsaerts, Peter; Struys, Tom; Boeckx, Nancy; Vandenberghe, Peter; Deroose, Christophe M; Verfaillie, Catherine M

    2017-06-01

    Myelodysplastic syndromes (MDS) are a group of clonal stem cell disorders affecting the normal hematopoietic differentiation process and leading to abnormal maturation and differentiation of all blood cell lineages. Treatment options are limited, and there is an unmet medical need for effective therapies for patients with severe cytopenias. We demonstrate that multipotent adult progenitor cells (MAPC) improve the function of hematopoietic progenitors derived from human MDS bone marrow (BM) by significantly increasing the frequency of primitive progenitors as well as the number of myeloid colonies. This effect was more pronounced in a non-contact culture, indicating the importance of soluble factors produced by the MAPC cells. Moreover, the cells did not stimulate the growth of the abnormal MDS clone, as shown by fluorescent in situ hybridization analysis on BM cells from patients with a known genetic abnormality. We also demonstrate that MAPC cells can provide stromal support for patient-derived hematopoietic cells. When MAPC cells were intravenously injected into a mouse model of MDS, they migrated to the site of injury and increased the hematopoietic function in diseased mice. The preclinical studies undertaken here indicate an initial proof of concept for the use of MAPC cell therapy in patients with MDS-related severe and symptomatic cytopenias and should pave the way for further investigation in clinical trials. Copyright © 2017. Published by Elsevier Inc.

  9. Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors

    PubMed Central

    Cheng, Hui; Ang, Heather Yin-Kuan; A. EL Farran, Chadi; Li, Pin; Fang, Hai Tong; Liu, Tong Ming; Kong, Say Li; Chin, Michael Lingzi; Ling, Wei Yin; Lim, Edwin Kok Hao; Li, Hu; Huber, Tara; Loh, Kyle M.; Loh, Yuin-Han; Lim, Bing

    2016-01-01

    Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into ‘induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase+ megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo. Molecularly, iHPs transcriptionally resemble native Kit+ hematopoietic progenitors. Mechanistically, reprogramming factor Lmo2 implements a hematopoietic programme in fibroblasts by rapidly binding to and upregulating the Hhex and Gfi1 genes within days. Moreover the reprogramming transcription factors also require extracellular BMP and MEK signalling to cooperatively effectuate reprogramming. Thus, the transcription factors that orchestrate embryonic hematopoiesis can artificially reconstitute this programme in developmentally distant fibroblasts, converting them into engraftable blood progenitors. PMID:27869129

  10. Conversion of human fibroblasts into monocyte-like progenitor cells

    PubMed Central

    Vitaloni, Marianna; Guenechea, Guillermo; Xia, Yun; Kurian, Leo; Dubova, Ilir; Bueren, Juan; Laricchia-Robbio, Leopoldo; Belmonte, Juan Carlos Izpisua

    2014-01-01

    Reprogramming technologies have emerged as a promising approach for future regenerative medicine. Here we report on the establishment of a novel methodology allowing for the conversion of human fibroblasts into Hematopoietic Progenitor-like Cells (HPC) with macrophage differentiation potential. SOX2 overexpression in human fibroblasts, a gene found to be upregulated during hematopoietic reconstitution in mice, induced the rapid appearance of CD34+ cells with a concomitant upregulation of mesoderm-related markers. Profiling of Cord Blood hematopoietic progenitor cell populations identified miR-125b as a factor facilitating commitment of SOX2-generated CD34+ cells to immature hematopoietic-like progenitor cells with grafting potential. Further differentiation towards the monocytic lineage resulted in the appearance of CD14+ cells with functional phagocytic capacity. In vivo transplantation of SOX2/miR-125b-generated CD34+ cells facilitated the maturation of the engrafted cells towards CD45+ cells and ultimately the monocytic/macrophage lineage. Altogether, our results indicate that strategies combining lineage conversion and further lineage specification by in vivo or in vitro approaches could help to circumvent long-standing obstacles for the reprogramming of human cells into hematopoietic cells with clinical potential. PMID:25175072

  11. No hot and luminous progenitor for Tycho's supernova

    NASA Astrophysics Data System (ADS)

    Woods, T. E.; Ghavamian, P.; Badenes, C.; Gilfanov, M.

    2017-09-01

    Type Ia supernovae have proven vital to our understanding of cosmology, both as standard candles and for their role in galactic chemical evolution; however, their origin remains uncertain. The canonical accretion model implies a hot and luminous progenitor that would ionize the surrounding gas out to a radius of 10-100 pc for 100,000 years after the explosion. Here, we report stringent upper limits on the temperature and luminosity of the progenitor of Tycho's supernova (SN 1572), determined using the remnant itself as a probe of its environment. Hot, luminous progenitors that would have produced a greater hydrogen ionization fraction than that measured at the radius of the present remnant ( 3 pc) can thus be excluded. This conclusively rules out steadily nuclear-burning white dwarfs (supersoft X-ray sources), as well as disk emission from a Chandrasekhar-mass white dwarf accreting approximately greater than 10-8 M⊙ yr-1 (recurrent novae; M⊙ is equal to one solar mass). The lack of a surrounding Strömgren sphere is consistent with the merger of a double white dwarf binary, although other more exotic scenarios may be possible.

  12. New Limits on the Nature of Type Ia Supernova Progenitors

    NASA Astrophysics Data System (ADS)

    Woods, Tyrone; Gilfanov, Marat

    2012-09-01

    To date, the question of which progenitor channel can reproduce the observed rate of type Ia supernovae (Sn Ia) remains unresolved. The single degenerate scenario posits that a white dwarf accretes stably from a companion star until reaching the Chandrasekhar mass. This requires that nuclear burning process at least 0.3 solar masses of hydrogen, the resulting energy release from which easily dominates the total luminosity of the WD (while nuclear burning is steady). In elliptical galaxies, measurements of the total observed soft X-ray emission have already placed strong upper limits on how much of this luminosity may be radiated in X-rays, limiting the possible contribution of "supersoft sources" to the Sn Ia rate. However, a population of single degenerate progenitors large enough to reproduce the Sn Ia rate would also easily provide among the dominant sources of ionizing photons, dramatically hardening the local ionizing UV background. This opens a new avenue for constraining the progenitors of Sn Ia, through consideration of the nebular emission now found in many early-type galaxies by large spectroscopic surveys such as SAURON. Modeling the predicted line ratios using the photoionization code MAPPINGS III, and demanding that they be consistent with those observed, allows us to place new constraints on the total contribution of the single degenerate channel to the Sn Ia rate in elliptical galaxies.

  13. Glial progenitor cell-based treatment of the childhood leukodystrophies

    PubMed Central

    Osorio, M. Joana; Goldman, Steven A.

    2017-01-01

    The childhood leukodystrophies comprise a group of hereditary disorders characterized by the absence, malformation or destruction of myelin. These disorders share common clinical, radiological and pathological features, despite their diverse molecular and genetic etiologies. Oligodendrocytes and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group of non-lysosomal metabolic leukodystrophies, may all be appropriate candidates for glial progenitor cell-based treatment. Nonetheless, a variety of specific challenges remain before this therapeutic strategy can be applied to children. These include timely diagnosis, before irreparable neuronal injury has ensued; understanding the natural history of the targeted disease; defining the optimal cell phenotype for each disorder; achieving safe and scalable cellular compositions, designing age-appropriate controlled clinical trials; and for autologous therapy of genetic disorders, achieving the safe genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease. PMID:27170209

  14. The supply of choline is important for fetal progenitor cells.

    PubMed

    Zeisel, Steven H

    2011-08-01

    Fetal progenitor cells proliferate, migrate, differentiate and undergo apoptosis at specific times during fetal development. Choline is needed by these cells for membrane synthesis and for methylation. There is growing evidence that this nutrient also modulates epigenetic regulation of gene expression in both neuronal and endothelial progenitor cells, thereby modifying brain development. It is likely that these mechanisms explain why, in rodent models, maternal dietary intake of choline influences both angiogenesis and neurogenesis in fetal hippocampus, and results in life-long changes in memory function. This also may explain why women eating diets low in choline have a greater risk of having a baby with a birth defect. Choline is mainly found in foods that contain fat and cholesterol, and intake of such foods has diminished in response dietary advice from nutritionists and physicians. Forty years ago, diets commonly contained choline-rich foods but now women in the USA tend to eat diets low in choline content. Premenopausal women normally may require less choline in their diet than do men and postmenopausal women, because estrogen induces the gene for the enzyme catalyzing endogenous biosynthesis of the choline-containing phospholipid phosphatidylcholine. However, many women have a single nucleotide polymorphism (SNP) that blocks the induction of endogenous biosynthesis, thereby making them require more dietary choline. When these women eat diets low in choline, the supply of this nutrient to the fetus is likely to be inadequate, and may perturb progenitor cell proliferation, migration, differentiation and apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Complete mitochondrial genome of the Southern catfish (Silurus meridionalis Chen) and Chinese catfish (S. asotus Linnaeus): Structure, phylogeny, and intraspecific variation.

    PubMed

    Wang, Q R; Xu, C; Xu, C R; Wang, R J

    2015-12-28

    The complete mitochondrial genome of the Southern catfish (Silurus meridionalis) and the Chinese catfish (S. asotus), was determined using the long and accurate polymerase chain reaction (LA-PCR) method. The mitochondrial DNA nucleotide sequences of S. meridionalis and S. asotus were compared with those of 47 other catfish species in the same order. The total length of mitochondrial DNA for S. meridionalis and S. asotus was 16,526 and 16,525 bp, respectively, and included 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a non-coding control region. This mitochondrial gene arrangement is identical to that observed in other Siluriformes. To determine the relative phylogenetic positions of S. meridionalis and S. asotus, and to discover phylogenetic relationships among 24 families of Siluriformes, analyses were conducted, based on mitochondrial DNA, 12S ribosomal RNA, 16S ribosomal RNA, and 13 protein-coding gene sequence data sets. Phylogenetic analyses were congruent with a basal split of the order into Clupeiformes, Characiformes, Cypriniformes, and Siluriformes, and supported a closer relationship of the Southern catfish (family Siluridae) and the Chinese catfish (family Siluridae) to Pimelodidae than to Bagridae. We concluded that these two species are part of a molecular clade that is different from that proposed in recent studies, in which Amblycipitidae appears as a sister group. Our results showed Amblycipitidae appearing as the most basal extant, and Bagridae appearing as a sister group of Cranoglanididae and Pangasiidae. The Siluriformes showed close phylogenetic relationship to the Characiformes.

  16. Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

    PubMed

    Bulatovic, Ivana; Månsson-Broberg, Agneta; Sylvén, Christer; Grinnemo, Karl-Henrik

    2016-02-01

    The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation). A variety of molecular disturbances in the factors regulating the specification and differentiation of these cells can cause congenital heart disease. This review explores the contribution of different cardiac progenitors to the embryonic heart development; the pathways and transcription factors guiding their expansion, migration, and functional differentiation; and the endogenous regenerative capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding these mechanisms will become the basis for understanding the dynamics of specific congenital heart disease as well as a means to develop therapy for fetal as well as postnatal cardiac defects and heart failure.

  17. Human fetal hepatic progenitor cells are distinct from, but closely related to, hematopoietic stem/progenitor cells.

    PubMed

    Chen, Qingfeng; Khoury, Maroun; Limmon, Gino; Choolani, Mahesh; Chan, Jerry K Y; Chen, Jianzhu

    2013-06-01

    Much controversy surrounds the identity and origin of human hepatic stem and progenitor cells in part because of a lack of small animal models in which the developmental potential of isolated candidate cell populations can be functionally evaluated. We show here that adoptive transfer of CD34(+) cells from human fetal liver into sublethally irradiated NOD-SCID Il2rg(-/-) (NSG) mice leads to an efficient development of not only human hematopoietic cells but also human hepatocyte-like cells in the liver of the recipient mice. Using this simple in vivo assay in combination with cell fractionation, we show that CD34(+) fetal liver cells can be separated into three distinct subpopulations: CD34(hi) CD133(hi), CD34(lo) CD133(lo), and CD34(hi) CD133(neg). The CD34(hi) CD133(hi) population contains hematopoietic stem/progenitor cells (HSPCs) as they give rise to T cells, B cells, NK cells, dendritic cells, and monocytes/macrophages in NSG mice and colony-forming unit (CFU)-GEMM cells in vitro. The CD34(lo) CD133(lo) population does not give rise to hematopoietic cells, but reproducibly generates hepatocyte-like cells in NSG mice and in vitro. The CD34(hi) CD133(neg) population only gives rise to CFU-GM and burst-forming unit-erythroid in vitro. Furthermore, we show that the CD34(lo) CD133(lo) cells express hematopoietic, hepatic, and mesenchymal markers, including CD34, CD133, CD117, epithelial cell adhesion molecule, CD73, albumin, α-fetal protein, and vimentin and transcriptionally are more closely related to HSPCs than to mature hepatocytes. These results show that CD34(lo) CD133(lo) fetal liver cells possess the hepatic progenitor cell properties and that human hepatic and hematopoietic progenitor cells are distinct, although they may originate from the same precursors in the fetal liver.

  18. Human adipose tissue contains erythroid progenitors expressing fetal hemoglobin

    PubMed Central

    Navarro, Amparo; Carbonell-Uberos, Francisco; Marín, Severiano; Miñana, María Dolores

    2013-01-01

    AIM: To investigate the origin of hematopoietic progenitors contained in the stromal vascular fraction (SVF) of human adipose tissue. METHODS: Tissue samples obtained from lipectomies were subjected to enzymatic digestion with collagenase to obtain a single-cell suspension. The centrifuged cell pellet, termed SVF, was separated immunomagnetically into CD45+ and CD45- cells and cultured in serum-free medium containing hematopoietic cytokines. The freshly isolated and cultured cells were evaluated to determine their ability to form hematopoietic colony-forming units in clonogenic assays and for the expression of certain hematopoietic transcription factors by reverse transcription-polymerase chain reaction; the gene expression level was compared to that in CD34+ hematopoietic progenitor cells from cord blood (CB) and adult peripheral blood (PB). To characterize erythroid progenitors, burst-forming units-erythroid (BFU-E) were developed in a semisolid medium under different culture conditions, and the hemoglobin composition and globin gene expression in the erythroid colonies were determined. RESULTS: The transcription factors SCL/TAL1, RUNX1, RUNX2 and GATA2 were expressed in both the CD45+ and CD45- SVF populations; however, in contrast to our observations in the CD34+ cells from CB and adult PB, GATA1 was not detected. Nevertheless, GATA1 could be detected in the SVF cells after seven days in culture, whereas its expression was upregulated in the CB CD34+ cells. The analysis of BFU-E-derived colonies revealed that virtually all erythroid cells produced by SVF cells expressed fetal hemoglobin, and the γ-globin mRNA levels ranged between those obtained in the adult- and neonatal-derived erythroid cells. Moreover, the SVF-derived erythroid cells synthesized similar levels of α- and β-globin mRNA, whereas the α-globin transcript levels were consistently higher those of β-globin in the cells derived from CB or PB CD34+ cells. Furthermore, although the cellular

  19. Mesenchymal Stem/Progenitor Cell Isolation from Tooth Extraction Sockets

    PubMed Central

    Nakajima, R.; Ono, M.; Hara, E.S.; Oida, Y.; Shinkawa, S.; Pham, H.T.; Akiyama, K.; Sonoyama, W.; Maekawa, K.; Kuboki, T.

    2014-01-01

    Bone marrow–derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach. It is well known that stem cells migrate from surrounding tissues and play important roles in wound healing. We thus hypothesized that stem/progenitor cells could be isolated from granulation tissue in the dental socket, and we subsequently collected granulation tissue from dog dental socket 3 d after tooth extraction. After enzyme digestion of the collected tissue, the cells forming colonies constituted the dental socket–derived stem/progenitor cells (dDSCs). Next, dDSCs were compared with dog BMSCs (dBMSCs) for phenotype characterization. A flow cytometric analysis showed that dDSCs were positive for CD44, CD90, and CD271 but negative for CD34 and CD45, similar to dBMSCs. dDSCs also exhibited osteogenic, adipogenic, and chondrogenic differentiation ability, similar to dBMSCs, with a higher capacity for colony formation, proliferation, and motility than dBMSCs. In addition, an in vivo ectopic bone formation assay showed that dDSCs and dBMSCs both induced hard tissue formation, although only dDSCs formed a fibrous tissue-like structure connected to the newly formed bone. Finally, we tested the ability of dDSCs to regenerate periodontal tissue in a one-wall defect model. The defects in the dDSC-transplanted group (β-TCP/PGA/dDSCs) were regenerated with cementum-like and periodontal ligament-like tissues and alveolar bone, whereas only bony tissue was observed in the control group (β-TCP/PGA). In conclusion, we identified and characterized a population of stem/progenitor cells in granulation tissue obtained from the dental socket that exhibited several characteristics similar to

  20. Mesenchymal stem/progenitor cell isolation from tooth extraction sockets.

    PubMed

    Nakajima, R; Ono, M; Hara, E S; Oida, Y; Shinkawa, S; Pham, H T; Akiyama, K; Sonoyama, W; Maekawa, K; Kuboki, T

    2014-11-01

    Bone marrow-derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach. It is well known that stem cells migrate from surrounding tissues and play important roles in wound healing. We thus hypothesized that stem/progenitor cells could be isolated from granulation tissue in the dental socket, and we subsequently collected granulation tissue from dog dental socket 3 d after tooth extraction. After enzyme digestion of the collected tissue, the cells forming colonies constituted the dental socket-derived stem/progenitor cells (dDSCs). Next, dDSCs were compared with dog BMSCs (dBMSCs) for phenotype characterization. A flow cytometric analysis showed that dDSCs were positive for CD44, CD90, and CD271 but negative for CD34 and CD45, similar to dBMSCs. dDSCs also exhibited osteogenic, adipogenic, and chondrogenic differentiation ability, similar to dBMSCs, with a higher capacity for colony formation, proliferation, and motility than dBMSCs. In addition, an in vivo ectopic bone formation assay showed that dDSCs and dBMSCs both induced hard tissue formation, although only dDSCs formed a fibrous tissue-like structure connected to the newly formed bone. Finally, we tested the ability of dDSCs to regenerate periodontal tissue in a one-wall defect model. The defects in the dDSC-transplanted group (β-TCP/PGA/dDSCs) were regenerated with cementum-like and periodontal ligament-like tissues and alveolar bone, whereas only bony tissue was observed in the control group (β-TCP/PGA). In conclusion, we identified and characterized a population of stem/progenitor cells in granulation tissue obtained from the dental socket that exhibited several characteristics similar to those

  1. Nucleostemin rejuvenates cardiac progenitor cells and antagonizes myocardial aging.

    PubMed

    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

    2015-01-20

    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 in 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. This study sought to demonstrate that NS preserves characteristics associated with "stemness" in CPCs and antagonizes myocardial senescence and aging. CPCs isolated from human fetal (fetal human cardiac progenitor cell [FhCPC]) and adult failing (adult human cardiac progenitor cell [AhCPC]) hearts, as well as young (young cardiac progenitor cell [YCPC]) and old mice (old cardiac progenitor cell [OCPC]), were studied for senescence characteristics and NS expression. Heterozygous knockout mice with 1 functional allele of NS (NS+/-) were used to demonstrate that NS preserves myocardial structure and function and slows characteristics of aging. NS expression is decreased in AhCPCs relative to FhCPCs, correlating with lowered proliferation potential and shortened telomere length. AhCPC characteristics resemble those of 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 a decline in cardiac function, an increase in senescence markers p53 and p16, telomere attrition

  2. Constraining Type Ia supernovae progenitor parameters via light curves

    NASA Astrophysics Data System (ADS)

    Sadler, Benjamin

    I study thermonuclear explosions of White Dwarf (WD) stars, or so-called Type Ia supernovae (SNe Ia). Higher precision is needed to determine the nature of the dark energy and to accomplish this we turn to secondary parameters of LC variation. I have devised a general scheme and developed a code to analyze large sets of LC data for these secondary parameter variations which is based on a combination of theoretical model template fitting and Principal Component Analysis. Novel methods for finding statistical trends in sparsely-sampled and non-coincidental light curve data are explored and utilized. In practice, data sets for different supernovae are inhomogeneous in time, time coverage and accuracy, but I have developed a method to remap these inhomogeneous data sets of large numbers of individual objects to a homogeneous data set centered in time and magnitude space from which we can obtain the external, primary, and secondary LC parameters of individual objects. The set of external parameters of a given SN include the time of its maximum light in various bands, its distance modulus, the extinction along the light path, and redshift corrections (K-corrections) due to cosmic expansion. I investigate the intrinsic primary parameter variation of SNe Ia via template fitting, and then probe the secondary LC variations using monochromatic differential analysis in the UBV bands. We use photometry from 25 SNe Ia which were recently and precisely observed by the Carnegie Supernova Project to analyze the presence of theoretical model-based differential LC signatures of Main-Sequence mass variation of the progenitor stars when they formed, central density variation of the WD at the time of the explosion, and metallicity Z variation in the progenitors. The light curves in the V band are found to provide the highest accuracy in determining the distance modulus, K-corrections, extinction, main-sequence mass and central density

  3. Kinetics of circulating progenitor cell mobilization during submaximal exercise.

    PubMed

    Niemiro, Grace M; Parel, Justin; Beals, Joseph; van Vliet, Stephan; Paluska, Scott A; Moore, Daniel R; Burd, Nicholas A; De Lisio, Michael

    2017-03-01

    Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors. Seven men [age = 25.3 ± 2.4 yr, body mass index = 23.5 ± 1.0 kg/m(2), peak O2 uptake (V̇o2peak) = 60.9 ± 2.74 ml·kg(-1)·min(-1)] ran on a treadmill for 60 min at 70% V̇o2peak Blood sampling occurred before (Pre), during [20 min (20e), 40 min (40e), 60 min (60e)], and after exercise [15 min (15p), 60 min (60p), 120 min (120p)] for quantification of CPCs (CD34(+)), HSPCs (CD34(+)/CD45(low)), HSCs (CD34(+)/CD45(low)/CD38(-)), CD34(+) MSCs (CD45(-)/CD34(+)/CD31(-)/CD105(+)), CD34(-) MSCs (CD45(-)/CD34(-)/CD31(-)/CD105(+)), and EPCs (CD45(-)/CD34(+)/CD31(+)) via flow cytometry. CPC concentration increased compared with Pre at 20e and 40e (2.7- and 2.4-fold, respectively, P < 0.05). HSPCs and HSCs increased at 20e compared with 60p (2.7- and 2.8-fold, respectively, P < 0.05), whereas EPCs and both MSC populations did not change. CXC chemokine ligand (CXCL) 12 (1.5-fold; P < 0.05) and stem cell factor (1.3-fold; P < 0.05) were increased at 40e and remained elevated postexercise. The peak increase in CPCs was positively correlated to concentration of endothelial cells during exercise with no relationship to CXCL12 and SCF. Our data show the kinetics of progenitor cell mobilization during exercise that could provide insight into cellular mediators of exercise-induced adaptations, and have implication for the use of exercise as an adjuvant therapy for CPC collection in hematopoietic stem cell transplant.NEW & NOTEWORTHY Using

  4. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    PubMed

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-06

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly.

  5. Temporally Distinct Six2-Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease.

    PubMed

    Zhou, Zhengfang; Wang, Jingying; Guo, Chaoshe; Chang, Weiting; Zhuang, Jian; Zhu, Ping; Li, Xue

    2017-01-24

    The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2(+)) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2(+) progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2(+) progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2(+) progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease.

  6. Endothelial progenitor cells in cardiovascular disease and chronic inflammation: from biomarker to therapeutic agent

    PubMed Central

    Grisar, Johannes C; Haddad, Francois; Gomari, Fatemeh A; Wu, Joseph C

    2012-01-01

    The discovery of endothelial progenitor cells in the 1990s challenged the paradigm of angiogenesis by showing that cells derived from hematopoietic stem cells are capable of forming new blood vessels even in the absence of a pre-existing vessel network, a process termed vasculogenesis. Since then, the majority of studies in the field have found a strong association between circulating endothelial progenitor cells and cardiovascular risk. Several studies have also reported that inflammation influences the mobilization and differentiation of endothelial progenitor cells. In this review, we discuss the emerging role of endothelial progenitor cells as biomarkers of cardiovascular disease as well as the interplay between inflammation and endothelial progenitor cell biology. We will also review the challenges in the field of endothelial progenitor cell-based therapy. PMID:22103609

  7. Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation.

    PubMed

    Nakano, Ichiro; Paucar, Andres A; Bajpai, Ruchi; Dougherty, Joseph D; Zewail, Amani; Kelly, Theresa K; Kim, Kevin J; Ou, Jing; Groszer, Matthias; Imura, Tetsuya; Freije, William A; Nelson, Stanley F; Sofroniew, Michael V; Wu, Hong; Liu, Xin; Terskikh, Alexey V; Geschwind, Daniel H; Kornblum, Harley I

    2005-08-01

    Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheres from MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)-positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain.

  8. Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells.

    PubMed

    Chou, Song; Flygare, Johan; Lodish, Harvey F

    2013-05-01

    We have developed a coculture system that establishes DLK(+) fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK(+) fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK(+) cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK(+) cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK(-) cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver.

  9. [Advances in Classification and Research Methods of Lung Epithelial Stem 
and Progenitor Cells].

    PubMed

    Deng, Minhua; Li, Jinhua; Gan, Ye; Chen, Ping

    2017-02-20

    Isolation and characterization of lung epithelial stem and progenitor cells and understanding of their specific role in lung physiopathology are critical for preventing and controlling lung diseases including lung cancer. In this review, we summarized recent advances in classification and research methods of lung epithelial stem and progenitor cells. Lung epithelial stem and progenitor cells were region-specific, which primarily included basal cells and duct cells in proximal airway, Clara cells, variant Clara cells, bronchioalveolar stem cells and induced krt5+ cells in bronchioles, type II alveolar cells and type II alveolar progenitor cells in alveoli. The research methods of lung epithelial stem and progenitor cells were mainly focused on lung injury models, lineage-tracing experiments, three dimensional culture, transplantation, chronic labeled cells and single-cell transcriptome analysis. Lastly, the potential relationship between lung epithelial stem and progenitor cells and lung cancer as well as lung cancer stem cell-targeted drug development were briefly reviewed.

  10. 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.

  11. 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

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

    PubMed

    Chang, Jessica B; Lee, Justine C

    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.

  13. 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.

  14. Biological behaviour and role of endothelial progenitor cells in vascular diseases.

    PubMed

    Zhang, Qiu-hua; She, Ming-peng

    2007-12-20

    To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007. The search term was "endothelial progenitor cells". Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used. Progenitor cells in bone marrow, peripheral blood and adventitia can differentiate into mature endothelial cells (ECs). The progenitor cells, which express certain surface markers including AC133, CD34 and KDR, enable restoration of the microcirculation and ECs when injury or ischaemia occurs. Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development. Moreover, their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors. Impairment of the progenitor cells might limit the regenerative capacity, even lead to the development of atherosclerosis or other vascular diseases. Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases. However, many challenges remain in understanding differentiation of endothelial progenitor cells, their mobilization and revascularization.

  15. 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.

  16. DENTAL FOLLICLE PROGENITOR CELL HETEROGENEITY IN THE DEVELOPING MOUSE PERIODONTIUM

    PubMed Central

    Luan, Xianghong; Ito, Yoshihiro; Dangaria, Smit; Diekwisch, Thomas G.H.

    2009-01-01

    As a developmental precursor for diverse periodontal tissues the dental follicle harbors great promise for periodontal tissue regeneration. However, development of optimal therapy awaits the answer to a key question that impinges on many issues in development; do adult progenitor tissues form a homogeneous cell population that differentiates into target tissues when they arrive at the site, or they contain heterogeneous cell populations that are committed to specific fates? In order to address the homogeneity/heterogeneity question we analyzed differentiation pathways and markers in several cloned dental follicle cell lines. Our studies revealed that each of our cloned dental follicle lines featured remarkably unique characteristics indicative of a separate and distinct lineage. One line, DF1 was high in proliferative activity while it did not display any mineralization behavior, suggesting that it might be related to a periodontal ligament-type lineage. DF2 was similar to DF1 but featured remarkably high alkaline phosphatase activity indicative of a highly undifferentiated state. DF3 matched the mineralization characteristics of a same stage alveolar bone line AB1 in terms of gene expression and von Kossa staining indicating that DF3 might be of cementoblastic or alveolar bone osteoblastic lineage. In order to verify the multilineage potential of the dental follicle for purposes of tissue engineering, a series of differentiation induction experiments was conducted. For identification purposes, characteristics of these heterogeneous follicular progenitor cells were compared with follicle components in tissue sections of the postnatal developing periodontium. The presence of heterogeneous cell populations in the dental follicle mirrors individual developmental pathways in the formation of the dental integument. The profound cellular heterogeneity of the dental follicle as an adult progenitor for tissue regeneration also suggests that heterogeneous cellular

  17. Superluminous supernova progenitors have a half-solar metallicity threshold

    NASA Astrophysics Data System (ADS)

    Chen, Ting-Wan; Smartt, Stephen J.; Yates, Rob M.; Nicholl, Matt; Krühler, Thomas; Schady, Patricia; Dennefeld, Michel; Inserra, Cosimo

    2017-09-01

    Host galaxy properties provide strong constraints on the stellar progenitors of superluminous supernovae. By comparing a sample of 19 low-redshift (z < 0.3) superluminous supernova hosts to galaxy populations in the local Universe, we show that sub-solar metallicities seem to be a requirement. All superluminous supernovae in hosts with high measured gas-phase metallicities are found to explode at large galactocentric radii, indicating that the metallicity at the explosion site is likely lower than the integrated host value. We found that superluminous supernova hosts do not always have star formation rates higher than typical star-forming galaxies of the same mass. However, we confirm that high absolute specific star formation rates are a feature of superluminous supernova host galaxies, but interpret this as simply a consequence of the anticorrelation between gas-phase metallicity and specific star formation rate and the requirement of on-going star formation to produce young, massive stars greater than ∼10-20 M⊙. Based on our sample, we propose an upper limit of ˜ 0.5 Z_{⊙} for forming superluminous supernova progenitors (assuming an N2 metallicity diagnostic and a solar oxygen abundance of 8.69). Finally, we show that if magnetar powering is the source of the extreme luminosity, then the required initial spins appear to be correlated with metallicity of the host galaxy. This correlation needs further work, but if it applies, it is a powerful link between the supernova parameters and nature of the progenitor population.

  18. Properties of SN Ia progenitors from light curves and spectra

    NASA Astrophysics Data System (ADS)

    Höflich, P.; Dragulin, P.; Mitchell, J.; Penney, B.; Sadler, B.; Diamond, T.; Gerardy, C.

    2013-04-01

    With recent advances in theory and observations, direct connections emerge between the progenitors of Type Ia Supernovae (SNe Ia) and the observed light curves and spectra. A direct link is important for our understanding of the supernovae physics, the diversity of SNe Ia and the use of SNe Ia for high-precision cosmology because the details of the explosion depends sensitively on the initial conditions and the explosion scenario(s) realized in nature. Do SNe Ia originate from SD- or DD systems, and do they lead to M Ch mass explosions or dynamical mergers? Does the statistical distribtion of SNe Ia depend on their environment which can be expected to change with redshift? In this contribution, we will exam from the theoretical point of view the tell-tails for this connection, their consistency with the observations, and future directions. In a first section, we present the physics of the explosion, light curves and spectral formation in a nutshell to help understanding the connection. For details of the progenitor evolution and explosion physics, we refer to reviews and the other contributions in this issue. Each of the topical sections starts with a brief general review followed by a more detailed discussion of specific results. Because the youth of the field, some bias is unavoidable towards results obtained within our collaborations (and FSU). The imprint of the metallicity, progenitor stars and properties such as the central density of the exploding WD are presented. IR spectroscopy, polarimetry and imaging of SNR remnants are discussed as a tool to test for the WD properties, magnetic fields and asymmetries. We discuss different classes of Type Ia supernovae, and their environment. Possible correlations between the spectroscopic and light curve properties of SN Ia are discussed. Finally, the overall emerging picture and future developments are discussed.

  19. Exfoliated Human Olfactory Neuroepithelium: A Source of Neural Progenitor Cells.

    PubMed

    Jiménez-Vaca, Ana L; Benitez-King, Gloria; Ruiz, Víctor; Ramírez-Rodríguez, Gerardo B; Hernández-de la Cruz, Beatriz; Salamanca-Gómez, Fabio A; González-Márquez, Humberto; Ramírez-Sánchez, Israel; Ortíz-López, Leonardo; Vélez-Del Valle, Cristina; Ordoñez-Razo, Rosa Ma

    2017-04-08

    Neural progenitor cells (NPC) contained in the human adult olfactory neuroepithelium (ONE) possess an undifferentiated state, the capability of self-renewal, the ability to generate neural and glial cells as well as being kept as neurospheres in cell culture conditions. Recently, NPC have been isolated from human or animal models using high-risk surgical methods. Therefore, it was necessary to improve methodologies to obtain and maintain human NPC as well as to achieve better knowledge of brain disorders. In this study, we propose the establishment and characterization of NPC cultures derived from the human olfactory neuroepithelium, using non-invasive procedures. Twenty-two healthy individuals (29.7 ± 4.5 years of age) were subjected to nasal exfoliation. Cells were recovered and kept as neurospheres under serum-free conditions. The neural progenitor origin of these neurospheres was determined by immunocytochemistry and qPCR. Their ability for self-renewal and multipotency was analyzed by clonogenic and differentiation assays, respectively. In the cultures, the ONE cells preserved the phenotype of the neurospheres. The expression levels of Nestin, Musashi, Sox2, and βIII-tubulin demonstrated the neural origin of the neurospheres; 48% of the cells separated could generate neurospheres, determining that they retained their self-renewal capacity. Neurospheres were differentiated in the absence of growth factors (EGF and FGF), and their multipotency ability was maintained as well. We were also able to isolate and grow human neural progenitor cells (neurospheres) through nasal exfoliates (non-invasive method) of the ONE from healthy adults, which is an extremely important contribution for the study of brain disorders and for the development of new therapies.

  20. Neural and oligodendrocyte progenitor cells: transferrin effects on cell proliferation

    PubMed Central

    Silvestroff, Lucas; Franco, Paula Gabriela; Pasquini, Juana María

    2013-01-01

    NSC (neural stem cells)/NPC (neural progenitor cells) are multipotent and self-renew throughout adulthood in the SVZ (subventricular zone) of the mammalian CNS (central nervous system). These cells are considered interesting targets for CNS neurodegenerative disorder cell therapies, and understanding their behaviour in vitro is crucial if they are to be cultured prior to transplantation. We cultured the SVZ tissue belonging to newborn rats under the form of NS (neurospheres) to evaluate the effects of Tf (transferrin) on cell proliferation. The NS were heterogeneous in terms of the NSC/NPC markers GFAP (glial fibrillary acidic protein), Nestin and Sox2 and the OL (oligodendrocyte) progenitor markers NG2 (nerve/glia antigen 2) and PDGFRα (platelet-derived growth factor receptor α). The results of this study indicate that aTf (apoTransferrin) is able to increase cell proliferation of SVZ-derived cells in vitro, and that these effects were mediated at least in part by the TfRc1 (Tf receptor 1). Since OPCs (oligodendrocyte progenitor cells) represent a significant proportion of the proliferating cells in the SVZ-derived primary cultures, we used the immature OL cell line N20.1 to show that Tf was able to augment the proliferation rate of OPC, either by adding aTf to the culture medium or by overexpressing rat Tf in situ. The culture medium supplemented with ferric iron, together with aTf, increased the DNA content, while ferrous iron did not. The present work provides data that could have a potential application in human cell replacement therapies for neurodegenerative disease and/or CNS injury that require the use of in vitro amplified NPCs. PMID:23368675

  1. Ovarian monocyte progenitor cells: phenotypic and functional characterization.

    PubMed

    Pascual, Cherry J; Sanberg, Paul R; Chamizo, Wilfredo; Haraguchi, Soichi; Lerner, Danika; Baldwin, Margi; El-Badri, Nagwa S

    2005-04-01

    Leukocytes of the macrophage lineage are abundant in the ovarian tissues and have an important function in both follicular development and regression of postovulatory follicles. In this study, we tested the hypothesis that continuous production of macrophages in the ovarian stroma is maintained by a resident population of progenitors. We established a long-term culture of ovarian follicular stromal cells from BALB/c and green fluorescent protein-transgenic (GFP-TG) C57BL/6 mice. Nonadherent cells were collected and tested for hematopoietic function in vitro and in vivo. Histological and ultrastructural analyses revealed a homogenous population of monocyte-like rounded cells. Nonadherent cells continued to proliferate in culture for several months without senescence. When plated at very low density in methylcellulose, these cells formed colonies consisting of monocyte-like cells. Ovarian monocyte-like cells reacted with CD45, CD11b, CD11c, and Ly6-Gr-1 cell surface markers. A distinct CD45low population within these cells reacted with CD117 (C-kit) surface marker, suggestive of a primitive hematopoietic progenitor. Fifty thousand nonadherent cells failed to provide radioprotection to lethally irradiated mice and thus were not considered to be equivalent to pluripotent hematopoietic stem cells. Ovarian nonadherent stromal cells were positive for alkaline phosphatase but lacked embryonic cell antigens stage-specific embryonic antigen (SSEA-1) and Oct-4. We conclude that in the ovaries, a higher requirement for macrophages is provided by a resident stromal population of progenitors whose progeny is restricted to the production of cells of the monocyte-macrophage lineage.

  2. Circulating perivascular progenitors: a target of PDGFR inhibition.

    PubMed

    Mancuso, Patrizia; Martin-Padura, Ines; Calleri, Angelica; Marighetti, Paola; Quarna, Jessica; Rabascio, Cristina; Braidotti, Paola; Bertolini, Francesco

    2011-09-15

    Cancer blood vessels consist of two interacting types of cells: inner lining endothelial cells (ECs) and surrounding perivascular cells (pericytes, vascular smooth muscle cells or mural cells). PDGFRbeta(CD140b)+ progenitor perivascular cells (PPC) can differentiate into pericytes and regulate vessel stability and vascular survival in tumors. Similarly to what we have done with circulating ECs and progenitors, we developed a flow cytometry procedure for the enumeration of circulating PPCs and the study of their viability in murine models of cancer and in cancer patients. DNA+CD45-CD31-CD140b+ cells were enumerated by six-colour flow cytometry, their morphology was studied by electron microscopy, PPC specificity confirmed by reverse trascription-PCR (RT-PCR) expression of CD140b mRNA, and viability assessed by Syto16 and 7AAD. In preclinical marrow transplantation studies, 9 ± 4% of circulating PPCs were derived from the marrow donor. PPCs were increased in cancer-bearing mice and in patients affected by some types of cancer. At variance with the kinetic of circulating endothelial progenitors, high-dose cyclophosphamide reduced the number of viable PPCs. The administration of sunitinib, a drug known to inhibit PDGFR, was associated in murine models and in cancer patients with an increase of apoptotic/necrotic circulating PPC, suggesting a direct targeting of these cells. PPC enumeration might be studied as a tool for the definition of the optimal biologic dose of anti-PDGFR drugs and investigated clinically as a possible predictive/prognostic tool in patients receiving anti-PDGFR drugs.

  3. 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.

  4. Impaired hematopoietic progenitor cells in trauma hemorrhagic shock.

    PubMed

    Kumar, Manoj; Bhoi, Sanjeev

    2016-01-01

    Hemorrhagic shock (HS) is the major cause of death during trauma. Mortality due to HS is about 50%. Dysfunction of hematopoietic progenitor cells (HPCs) has been observed during severe trauma and HS. HS induces the elevation of cytokines, granulocyte-colony stimulating factor (G-CSF), peripheral blood HPCs, and circulating catecholamines, and decreases the expression of erythropoietin receptor connected with suppression of HPCs. Impaired HPCs may lead to persistent anemia and risk of susceptibility to infection, sepsis, and MOF. There is a need to reactivate impaired HPCs during trauma hemorrhagic shock.

  5. Determining the progenitors of supernovae with early robotic observations

    NASA Astrophysics Data System (ADS)

    Howell, Andrew

    2015-08-01

    We present results from the LCOGT Supernova Key Project, a three year program to obtain lightcurves and spectra of 600 supernovae. The Las Cumbres Observatory Global Telescope Network is a network of eleven robotic 1m and 2m telescopes located at 5 sites around the world. With this facility long term monitoring of transient phenomena is possible, as are nearly instantaneous observations. We report on both core-collapse and thermonuclear supernovae observed within days of explosion, allowing insight into their progenitor stars.

  6. Determining the progenitors of supernovae with early robotic observations

    NASA Astrophysics Data System (ADS)

    Howell, Andrew

    We present results from the LCOGT Supernova Key Project, a three year program to obtain lightcurves and spectra of 600 supernovae. The Las Cumbres Observatory Global Telescope Network is a network of eleven robotic 1m and 2m telescopes located at 5 sites around the world. With this facility long term monitoring of transient phenomena is possible, as are nearly instantaneous observations. We report on both core-collapse and thermonuclear supernovae observed within days of explosion, allowing insight into their progenitor stars.

  7. Genomewide Chromatin Maps Derived from Limited Numbers of Hematopoietic Progenitors

    PubMed Central

    Adli, Mazhar; Zhu, Jiang; Bernstein, Bradley E.

    2010-01-01

    Current methods for whole genome mapping of protein-DNA interactions, performed by coupling chromatin immunoprecipitation with high-throughput sequencing (ChIP-Seq), require large amounts of starting materials which precludes their application to rare cell types. Here, we combine a high-sensitivity ChIP assay with a novel library preparation procedure to map histone modifications in as few as 10,000 cells. We apply the technique to characterize murine hematopoietic progenitors and thereby gain insight into their developmental program. PMID:20622861

  8. SN Ia archaeology: Searching for the relics of progenitors past

    NASA Astrophysics Data System (ADS)

    Woods, Tyrone E.; Gilfanov, Marat; Clocchiatti, Alejandro; Rest, Armin

    2016-06-01

    Despite the critical role that SNe Ia play in the chemical enrichment of the Universe and their great importance in measuring cosmological distances, we still don't know for certain how they arise. In the canonical form of the ``single-degenerate'' scenario, a white dwarf grows through the nuclear burning of matter accreted at its surface from some companion star. This renders it a hot, luminous object (a supersoft X-ray source or SSS, 10^5-10^6K, 10^{38} erg/s) for up to a million years prior to explosion. Past efforts to directly detect the progenitors of very recent, nearby SNe Ia in archival soft X-ray images have produced only upper limits, and are only constraining assuming progenitors with much higher temperatures than known SSSs. In this talk, I will outline an alternative approach: given that such objects should be strong sources of ionizing radiation, one may instead search the environment surrounding nearby SN Ia remnants for interstellar matter ionized by the progenitor. Such fossil nebulae should extend out to tens of parsecs and linger for roughly the recombination timescale in the ISM, of order 10,000 — 100,000 years. Progress on this front has been hampered by the failure to detect nebulae surrounding most known SSSs using 1m class telescopes in the early 1990s. I will present new benchmark calculations for the emission-line nebulae expected to surround such objects, demonstrating that previous non-detections are entirely consistent with the low ISM densities expected in the vicinity of most SN Ia progenitors (Woods & Gilfanov, 2016). Modern large optical telescopes are now well able to reach the required limiting surface brightness needed to find such faint emission. With this in mind, I will introduce our new narrow-band survey for fossil nebulae surrounding young Magellanic SN Ia remnants and SSSs, already underway using the Magellan Baade telescope (PI: Alejandro Clocchiatti). In addition to opening a new era of SN Ia archaeology, I will show

  9. Regulation of Mammary Progenitor Cells by p53 and Parity

    DTIC Science & Technology

    2011-01-01

    family was shown to be depleted in the m ammary progenitor cells and highly expressed in the m ore differentiated cell types and the let-7c sensor...apoptosis and tumor suppression. Nat. Med. 4, 835-838 (1998). 21. Giono, L. E. & Manfredi, J. J. The p53 tumor suppressor participates in multiple ...Schauble, B., zur, H. A., Esteve, J. & Ohgaki, H. Tumors associated with p53 germline mutations: a synopsis of 91 families . Am. J. Pathol. 150, 1-13 (1997

  10. The Standing Accretion Shock Instability: Enhanced Growth in Rotating Progenitors

    NASA Astrophysics Data System (ADS)

    Blondin, John M.; Gipson, Emily; Harris, Sawyer; Mezzacappa, Anthony

    2017-02-01

    We investigate the effect of progenitor rotation on the standing accretion shock instability (SASI) using two- and three-dimensional hydrodynamic simulations. We find that the growth rate of the SASI is a near-linearly increasing function of the specific angular momentum in the accreting gas. Both the growth rate and the angular frequency in the two-dimensional model with cylindrical geometry agree well with previous linear stability analyses. When excited by very small random perturbations, a one-armed spiral mode dominates the small rotation rates predicted by current stellar evolution models, while progressively higher-order modes are seen as the specific angular momentum increases.

  11. Methylene blue promotes quiescence of rat neural progenitor cells.

    PubMed

    Xie, Luokun; Choudhury, Gourav R; Wang, Jixian; Park, Yong; Liu, Ran; Yuan, Fang; Zhang, Chun-Li; Yorio, Thomas; Jin, Kunlin; Yang, Shao-Hua

    2014-01-01

    Neural stem cell-based treatment holds a new therapeutic opportunity for neurodegenerative disorders. Here, we investigated the effect of methylene blue on proliferation and differentiation of rat neural progenitor cells (NPCs) both in vitro and in vivo. We found that methylene blue inhibited proliferation and promoted quiescence of NPCs in vitro without affecting committed neuronal differentiation. Consistently, intracerebroventricular infusion of methylene blue significantly inhibited NPC proliferation at the subventricular zone (SVZ). Methylene blue inhibited mTOR signaling along with down-regulation of cyclins in NPCs in vitro and in vivo. In summary, our study indicates that methylene blue may delay NPC senescence through enhancing NPCs quiescence.

  12. On the progenitor of SN 2008ax in NGC 4490

    NASA Astrophysics Data System (ADS)

    Li, Weidong

    2008-03-01

    W. Li, University of California, Berkeley (UCB); S. D. Van Dyk, Spitzer Science Center, California Institute of Technology; J.-C. Cuillandre, Canada-France-Hawaii Telescope (CFHT) Corporation; and A. V. Filippenko, R. J. Foley, R. Chornock, N. Smith, and X. Wang (all UCB), report that they have isolated a possible progenitor for the young type-II SN 2008ax in Hubble Space Telescope images of NGC 4490 (Snapshot program 5446; GO/DD program 9042) taken with the Wide Field Planetary Camera 2 (WFPC2).

  13. Interleukin-1 regulates hematopoietic progenitor and stem cells in the midgestation mouse fetal liver

    PubMed Central

    Orelio, Claudia; Peeters, Marian; Haak, Esther; van der Horn, Karin; Dzierzak, Elaine

    2009-01-01

    Background Hematopoietic progenitors are generated in the yolk sac and aorta-gonad-mesonephros region during early mouse development. At embryonic day 10.5 the first hematopoietic stem cells emerge in the aorta-gonad-mesonephros. Subsequently, hematopoietic stem cells and progenitors are found in the fetal liver. The fetal liver is a potent hematopoietic site, playing an important role in the expansion and differentiation of hematopoietic progenitors and hematopoietic stem cells. However, little is known concerning the regulation of fetal liver hematopoietic stem cells. In particular, the role of cytokines such as interleukin-1 in the regulation of hematopoietic stem cells in the embryo has been largely unexplored. Recently, we observed that the adult pro-inflammatory cytokine interleukin-1 is involved in regulating aorta-gonad-mesonephros hematopoietic progenitor and hematopoietic stem cell activity. Therefore, we set out to investigate whether interleukin-1 also plays a role in regulating fetal liver progenitor cells and hematopoietic stem cells. Design and Methods We examined the interleukin-1 ligand and receptor expression pattern in the fetal liver. The effects of interleukin-1 on hematopoietic progenitor cells and hematopoietic stem cells were studied by FACS and transplantation analyses of fetal liver explants, and in vivo effects on hematopoietic stem cell and progenitors were studied in Il1r1−/− embryos. Results We show that fetal liver hematopoietic progenitor cells express the IL-1RI and that interleukin-1 increases fetal liver hematopoiesis, progenitor cell activity and promotes hematopoietic cell survival. Moreover, we show that in Il1r1−/− embryos, hematopoietic stem cell activity is impaired and myeloid progenitor activity is increased. Conclusions The IL-1 ligand and receptor are expressed in the midgestation liver and act in the physiological regulation of fetal liver hematopoietic progenitor cells and hematopoietic stem cells. PMID

  14. Three-dimensional perfusion cultivation of human cardiac-derived progenitors facilitates their expansion while maintaining progenitor state.

    PubMed

    Kryukov, Olga; Ruvinov, Emil; Cohen, Smadar

    2014-11-01

    The therapeutic application of autologous cardiac-derived progenitor cells (CPCs) requires a large cell quantity generated under defined conditions. Herein, we investigated the applicability of a three-dimensional (3D) perfusion cultivation system to facilitate the expansion of CPCs harvested from human heart biopsies and characterized by a relatively high percentage of c-kit(+) cells. The cells were seeded in macroporous alginate scaffolds and after cultivation for 7 days under static conditions, some of the constructs were transferred into a perfusion bioreactor, which was operated for an additional 14 days. A robust and highly reproducible human CPC (hCPC) expansion of more than seven-fold was achieved under the 3D perfusion culture conditions, while under static conditions, the expansion of CPCs was limited only to the first 7 days, after which it leveled-off. On day 21 of perfusion cultivation, the expanded cells exhibited a higher expression level of the progenitor marker c-kit, suggesting that the c-kit-positive CPCs are the main cell population undergoing proliferation. The profile of the spontaneous differentiation in the perfused construct was different from that in the static cultivated constructs; genes typical for cardiac and endothelial cell lineages were more widely expressed in the perfused constructs. By contrast, the differentiation to osteogenic (Von Kossa staining and alkaline phosphatase activity) and adipogenic (Oil Red staining) lineages was reduced in the perfused constructs compared with static cultivated constructs. Collectively, our results indicate that 3D perfusion cultivation mode is an appropriate system for robust expansion of human CPCs while maintaining their progenitor state and differentiation potential into the cardiovascular cell lineages.

  15. 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

  16. 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

  17. 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.

  18. Derivation of multipotent progenitors from human circulating CD14+ monocytes.

    PubMed

    Seta, Noriyuki; Kuwana, Masataka

    2010-07-01

    Circulating CD14(+) monocytes are originated from hematopoietic stem cells in the bone marrow and believed to be committed precursors for phagocytes, such as macrophages. Recently, we have reported a primitive cell population termed monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMCs are derived from circulating CD14(+) monocytes, but circulating precursors for MOMCs still remain undetermined. Comparative analysis of gene expression profiles of MOMCs and other monocyte-derived cells has revealed that embryonic stem cell markers, Nanog and Oct-4, are specifically expressed by MOMCs. In vitro generation of MOMCs requires binding to fibronectin and exposure to soluble factors derived from activated platelets. MOMCs contain progenitors with capacity to differentiate into a variety of nonphagocytes, including bone, cartilage, fat, skeletal and cardiac muscle, neuron, and endothelium, indicating that circulating monocytes are more multipotent than previously thought. In addition, MOMCs are capable of promoting ex vivo expansion of human hematopoietic progenitor cells through direct cell-to-cell contact and secretion of a variety of hematopoietic growth factors. These findings obtained from the research on MOMCs indicate that CD14(+) monocytes in circulation are involved in a variety of physiologic functions other than innate and acquired immune responses, such as repair and regeneration of the damaged tissue.

  19. Close Split of Sorghum and Maize Genome Progenitors

    PubMed Central

    Swigoňová, Zuzana; Lai, Jinsheng; Ma, Jianxin; Ramakrishna, Wusirika; Llaca, Victor; Bennetzen, Jeffrey L.; Messing, Joachim

    2004-01-01

    It is generally believed that maize (Zea mays L. ssp. mays) arose as a tetraploid; however, the two progenitor genomes cannot be unequivocally traced within the genome of modern maize. We have taken a new approach to investigate the origin of the maize genome. We isolated and sequenced large genomic fragments from the regions surrounding five duplicated loci from the maize genome and their orthologous loci in sorghum, and then we compared these sequences with the orthologous regions in the rice genome. Within the studied segments, we identified 11 genes that were conserved in location, order, and orientation. We performed phylogenetic and distance analyses and examined the patterns of estimated times of divergence for sorghum and maize gene orthologs and also the time of divergence for maize orthologs. Our results support a tetraploid origin of maize. This analysis also indicates contemporaneous divergence of the ancestral sorghum genome and the two maize progenitor genomes about 11.9 million years ago (Mya). On the basis of a putative conversion event detected for one of the genes, tetraploidization must have occurred before 4.8 Mya, and therefore, preceded the major maize genome expansion by gene amplification and retrotransposition. PMID:15466289

  20. Resident cardiac progenitor cells: at the heart of regeneration.

    PubMed

    Bollini, Sveva; Smart, Nicola; Riley, Paul R

    2011-02-01

    Stem cell therapy has recently emerged as an innovative strategy over conventional cardiovascular treatments to restore cardiac function in patients affected by ischemic heart disease. Various stem cell populations have been tested and their potential for cardiac repair has been analyzed. Embryonic stem cells retain the greatest differentiation potential, but concerns persist with regard to their immunogenic and teratogenic effects. Although adult somatic stem cells are not tumourigenic and easier to use in an autologous setting, they exist in small numbers and possess reduced differentiation potential. Traditionally the heart was considered to be a post-mitotic organ; however, this dogma has recently been challenged with the identification of a reservoir of resident stem cells, defined as cardiac progenitor cells (CPCs). These endogenous progenitors may represent the best candidates for cardiovascular cell therapy, as they are tissue-specific, often pre-committed to a cardiac fate, and display a greater propensity to differentiate towards cardiovascular lineages. This review will focus on current research into the biology of CPCs and their regenerative potential. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  1. 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.

  2. Progressive induction of hepatocyte progenitor cells in chronically injured liver

    PubMed Central

    Tanimizu, Naoki; Ichinohe, Norihisa; Yamamoto, Masahiro; Akiyama, Haruhiko; Nishikawa, Yuji; Mitaka, Toshihiro

    2017-01-01

    Differentiated epithelial cells show substantial lineage plasticity upon severe tissue injuries. In chronically injured mouse livers, part of hepatocytes become Sry-HMG box containing 9 (Sox9) (+) epithelial cell adhesion molecule (−) hepatocyte nuclear factor 4 α (+) biphenotypic hepatocytes. However, it is not clear whether all Sox9+ hepatocytes uniformly possess cellular properties as hepatocyte progenitors. Here, we examined the microarray data comparing Sox9+ hepatocytes with mature hepatocytes and identified CD24 as a novel marker for biphenotypic hepatocytes. Immunohistochemical analyses showed that part of Sox9+ hepatocytes near expanded ductular structures expressed CD24 in the liver injured by 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet and by bile duct ligation. Indeed, Sox9+ hepatocytes could be separated into CD24− and CD24+ cells by fluorescence activated cell sorting. The ratio of CD24+ cells against CD24− ones in Sox9+ hepatocytes gradually increased while DDC-injury progressed and colony-forming capability mostly attributed to CD24+ cells. Although hepatocyte markers were remarkably downregulated in of Sox9+ CD24+ hepatocytes, they re-differentiated into mature hepatocytes in vitro and in vivo. Our current results demonstrate that the emergence of biphenotypic hepatocytes is a sequential event including the transition from CD24− and CD24+ status, which may be a crucial step for hepatocytes to acquire progenitor properties. PMID:28051157

  3. Liver progenitor cells-mediated liver regeneration in liver cirrhosis.

    PubMed

    Shang, Haitao; Wang, Zhijun; Song, Yuhu

    2016-05-01

    Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. In cirrhotic liver where hepatocytes proliferation is compromised, liver progenitor cells (LPCs) are activated and then differentiated into hepatocytes and cholangiocytes, leading to the generation of regenerative nodules and functional restoration. Here, we summarize and discuss recent findings on the mechanisms underlying LPCs-mediated regeneration in liver cirrhosis. Firstly, we provide recent research on the mechanism underlying LPCs activation in severe or chronic liver injury. Secondly, we present new and exciting data on exploring the origin of LPCs, which reveal that the hepatocytes give rise to duct-like progenitors that then differentiate back into hepatocytes in chronic liver injury or liver cirrhosis. Finally, we highlight recent findings from the literature exploring the role of LPCs niche in directing the behavior and fate of LPCs. This remarkable insight into the cellular and molecular mechanisms of LPCs-mediated regeneration in liver cirrhosis will provide a basis for translating this knowledge into clinical application.

  4. Massive star evolution: luminous blue variables as unexpected supernova progenitors

    NASA Astrophysics Data System (ADS)

    Groh, J. H.; Meynet, G.; Ekström, S.

    2013-02-01

    Stars more massive than about 8 M⊙ end their lives as a supernova (SN), an event of fundamental importance Universe-wide. Theoretically, these stars have been expected to be either at the red supergiant, blue supergiant, or Wolf-Rayet stage before the explosion. We performed coupled stellar evolution and atmospheric modeling of stars with initial masses between 20 M⊙ and 120 M⊙. We found that the 20 M⊙ and 25 M⊙ rotating models, before exploding as SN, have spectra that do not resemble any of the aforementioned classes of massive stars. Rather, they have remarkable similarities with rare, unstable massive stars known as luminous blue variables (LBV). While observations show that some SNe seem to have had LBVs as progenitors, no theoretical model had yet predicted that a star could explode at this stage. Our models provide theoretical support for relatively low-luminosity LBVs exploding as SN in the framework of single stellar evolution. This is a significant shift in paradigm, meaning that a fraction of LBVs could be the end stage of massive star evolution, rather than a transitory evolutionary phase. We suggest that type IIb SN could have LBV as progenitors, and a prime example could be SN 2008ax.

  5. Reduced in vitro erythroid progenitor cell growth in bronchial cancer.

    PubMed Central

    Masters, G S; Baines, P; Bailey-Wood, R; Gorvett, T; Littlewood, T; Bentley, P; Parry-Jones, H; Jacobs, A

    1987-01-01

    Peripheral blood and bone marrow were studied in 21 men with disseminated untreated bronchial cancer in an attempt to define abnormalities of erythropoiesis associated with the development of anaemia. Haemoglobin concentration at or below 13 g/dl was present in 13 cases. Marrow morphology was normal in all cases except one, in which small numbers of tumour cells were found. Clonal assay of erythroid progenitors showed a significant decrease in the number of BFU-E (p = 0.03) and CFU-E (p = 0.01) compared with cultures from normal marrow (12 subjects). The growth of granulocyte and macrophage progenitors (GM-CFCs) was similar in patients with bronchial cancer and normal subjects. When normal marrow was incubated in the presence of serum from bronchial cancer patients, no inhibitory factors could be detected either for BFU-E or CFU-E growth. In all patients circulating T8 numbers were significantly raised (p = 0.0002). Consequently, the median T4:T8 ratio in blood was 1.2, and this was significantly lower than the ratio of 1.7 found in 20 normal subjects (p = 0.036). In 18 patients the bone marrow T4:T8 ratio of 1.1 was significantly lower than the ratio of 2.9 found in seven normal subjects (p = 0.04). Total blood white cell counts, neutrophils, and monocyte numbers were also increased (p = 0.0001; p = 0.0001; p = 0.002). PMID:3818975

  6. 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

  7. Adult stem cell and mesenchymal progenitor theories of aging.

    PubMed

    Fukada, So-Ichiro; Ma, Yuran; Uezumi, Akiyoshi

    2014-01-01

    Advances in medical science and technology allow people live longer lives, which results in age-related problems. Humans cannot avoid the various aged-related alterations of aging; in other words, humans cannot remain young at molecular and cellular levels. In 1956, Harman proposed the "free radical theory of aging" to explain the molecular mechanisms of aging. Telomere length, and accumulation of DNA or mitochondrial damage are also considered to be mechanisms of aging. On the other hand, stem cells are essential for maintaining tissue homeostasis by replacing parenchymal cells; therefore, the stem cell theory of aging is also used to explain the progress of aging. Importantly, the stem cell theory of aging is likely related to other theories. In addition, recent studies have started to reveal the essential roles of tissue-resident mesenchymal progenitors/stem cells/stromal cells in maintaining tissue homeostasis, and some evidence of their fundamental roles in the progression of aging has been presented. In this review, we discuss how stem cell and other theories connect to explain the progress of aging. In addition, we consider the mesenchymal progenitor theory of aging to describing the process of aging.

  8. Notch3 marks clonogenic mammary luminal progenitor cells in vivo

    PubMed Central

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis

    2013-01-01

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells. PMID:24100291

  9. Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

    PubMed

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

    2013-10-14

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

  10. Apheresis techniques for collection of peripheral blood progenitor cells.

    PubMed

    Moog, Rainer

    2004-12-01

    The combination of effective mobilisation protocols and efficient use of apheresis machines has caused peripheral blood progenitor cells (PBPC) transplantation to grow rapidly. The development of apheresis technology has improved over the years. Today PBSC procedures have changed towards systems to minimise operator interaction and to reduce the collection of undesired cells such as polymorphonuclear cells and platelets using functionally closed, sterile environments for PBSC collection in keeping with Good Manufacturing Practice guidelines. Blood cell separators with continuous flow technique allow the processing of more blood than intermittent flow devices resulting in higher PBSC yields. Large volume leukapheresis with the processing of 3-4-fold donor's/patient's blood volume can increase the number of collected progenitor cells. Therefore, intermittent flow cell separators are indicated if only single vein access is available. Anticoagulant induced hypocalcaemia is an often observed side effect in long lasting PBPC harvesting and monitoring of electrolytes should be performed especially at the end of the apheresis procedure to supplement low levels of potassium, calcium or magnesium. Refinement and improvement of collection techniques continue to add to the armamentarium of current approaches for cancer and non-malignant conditions and will enable future strategies.

  11. Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells

    PubMed Central

    Jadali, Azadeh; Song, Zhichao; Ruiz-Laureano, Alejandra S.; Toro-Ramos, Alana

    2017-01-01

    Use of human induced pluripotent stem cells (iPSC) or embryonic stem cells (ESC) for cell replacement therapies holds great promise. Several limitations including low yields and heterogeneous populations of differentiated cells hinder the progress of stem cell therapies. A fate restricted immortalized multipotent otic progenitor (iMOP) cell line was generated to facilitate efficient differentiation of large numbers of functional hair cells and spiral ganglion neurons (SGN) for inner ear cell replacement therapies. Starting from dissociated cultures of single iMOP cells, protocols that promote cell cycle exit and differentiation by growth factor (bFGF) withdrawal were described. A significant decrease in proliferating cells after bFGF withdrawal was confirmed using an EdU cell proliferation assay. Concomitant with a decrease in proliferation, successful differentiation resulted in expression of molecular markers and morphological changes. Immunostaining of Cdkn1b (p27KIP) and Cdh1 (E-cadherin) in iMOP-derived otospheres was used as an indicator for differentiation into inner ear sensory epithelia while immunostaining of Cdkn1b and Tubb3 (neuronal β-tubulin) was used to identify iMOP-derived neurons. Use of iMOP cells provides an important tool for understanding cell fate decisions made by inner ear neurosensory progenitors and will help develop protocols for generating large numbers of iPSC or ESC-derived hair cells and SGNs. These methods will accelerate efforts for generating otic cells for replacement therapies. PMID:26780605

  12. Bone marrow-derived progenitor cells in pulmonary fibrosis.

    PubMed

    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 alpha-smooth muscle actin. Treatment of isolated GFP(+) fibroblasts with TGF-beta 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-1 alpha and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells.

  13. Adenosine signaling promotes hematopoietic stem and progenitor cell emergence.

    PubMed

    Jing, Lili; Tamplin, Owen J; Chen, Michael J; Deng, Qing; Patterson, Shenia; Kim, Peter G; Durand, Ellen M; McNeil, Ashley; Green, Julie M; Matsuura, Shinobu; Ablain, Julien; Brandt, Margot K; Schlaeger, Thorsten M; Huttenlocher, Anna; Daley, George Q; Ravid, Katya; Zon, Leonard I

    2015-05-04

    Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1(+)/cmyb(+) HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl(+) hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.

  14. 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

  15. THE PROGENITOR OF SN 2011ja: CLUES FROM CIRCUMSTELLAR INTERACTION

    SciTech Connect

    Chakraborti, Sayan; Ray, Alak; Yadav, Naveen; Smith, Randall; Ryder, Stuart; Sutaria, Firoza; Dwarkadas, Vikram V.; Chandra, Poonam; Pooley, David; Roy, Rupak

    2013-09-01

    Massive stars, possibly red supergiants, which retain extended hydrogen envelopes until core collapse, produce Type II plateau (IIP) supernovae. The ejecta from these explosions shocks the circumstellar matter originating from the mass loss of the progenitor during the final phases of its life. This interaction accelerates particles to relativistic energies which then lose energy via synchrotron radiation in the shock-amplified magnetic fields and inverse Compton scattering against optical photons from the supernova. These processes produce different signatures in the radio and X-ray parts of the electromagnetic spectrum. Observed together, they allow us to break the degeneracy between shock acceleration and magnetic field amplification. In this work, we use X-rays observations from the Chandra and radio observations from the Australia Telescope Compact Array to study the relative importance of processes which accelerate particles and those which amplify magnetic fields in producing the non-thermal radiation from SN 2011ja. We use radio observations to constrain the explosion date. Multiple Chandra observations allow us to probe the history of variable mass loss from the progenitor. The ejecta expands into a low-density bubble followed by interaction with a higher density wind from a red supergiant consistent with M{sub ZAMS} {approx}> 12 M{sub Sun }. Our results suggest that a fraction of Type IIP supernovae may interact with circumstellar media set up by non-steady winds.

  16. Progenitor Cell Self-renewal and Cyclic Neutropenia

    PubMed Central

    Dingli, David; Antal, Tibor; Traulsen, Arne; Pacheco, Jorge M.

    2009-01-01

    Cyclic neutropenia (CN) is a rare genetic disorder where patients experience regular cycling of neutrophils and various other hematopoietic lineages. The nadir in the neutrophil count is the main source of problems due to the risk of life-threatening infections. Patients with CN benefit from G-CSF therapy although cycling persists. Mutations in the neutrophil elastase gene (ELA2) have been found in more than half of the patients with CN. However, neither the connection between phenotypic expression of ELA2 and CN nor the mechanism of cycling are known. Recently a multi-compartment model of hematopoiesis that couples stem cell replication with marrow output was proposed. In the following, we couple this model of hematopoiesis with a linear feedback mechanism via G-CSF. We propose that the phenotypic effect of ELA2 mutations leads to a reduction in self-renewal of granulocytic progenitors. The body responds by an overall relative increase of G-CSF and increasing progenitor cell self-renewal leading to cell count cycling. The model is compatible with the available experimental data and makes testable predictions. PMID:19397594

  17. Lung stem and progenitor cells in tissue homeostasis and disease.

    PubMed

    Leeman, Kristen T; Fillmore, Christine M; Kim, Carla F

    2014-01-01

    The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of cell surface markers, these cells can also be isolated from murine and human lung and tested in 3D culture systems and in vivo transplant assays. The pathology of devastating lung diseases, including lung cancers, is likely in part due to dysregulation and dysfunction of lung stem cells. More precise characterization of stem cells with identification of new, unique markers; improvement in isolation and transplant techniques; and further development of functional assays will ultimately lead to new therapies for a host of human lung diseases. In particular, lung cancer biology may be greatly informed by findings in normal lung stem cell biology as evidence suggests that lung cancer is a disease that begins in, and may be driven by, neoplastic lung stem cells. © 2014 Elsevier Inc. All rights reserved.

  18. Potential implications of vascular wall resident endothelial progenitor cells.

    PubMed

    Ergün, Süleyman; Tilki, Derya; Hohn, Hans-Peter; Gehling, Ursula; Kilic, Nerbil

    2007-11-01

    A rapidly increasing body of data suggests an essential role of endothelial progenitor cells (EPCs) in vascular regeneration, formation of new vessels in cardiovascular diseases and also in tumor vasculogenesis. Moreover, recent data obtained from clinical studies with anti-angiogenic drugs in tumor therapy or with pro-angiogenic stimuli in ischemic disorders implicate a predictive role of the number of EPCs circulating in the peripheral blood in monitoring of these diseases. However, there is still some controversial data regarding the relevance of the EPCs in vascular formation depending on models used and diseases studied. One of the essential prerequisites for a better understanding of the whole contribution of EPCs to vascular formation in adult, a process called postnatal vasculogenesis, is to identify their exact sources. We could recently discover the existence of EPCs in a distinct zone of the vascular wall of large and middle sized adult blood vessels and showed that these cells are capable to differentiate into mature endothelial cells, to form capillary sprouts in arterial ring assay and to build vasa vasorum-like structures within the vascular wall. They also can be mobilized very rapidly from the vascular wall by tumor cells. This review will discuss the functional implications of these vascular wall resident endothelial progenitor cells (VW-EPCs) in relation to those of EPCs circulating in peripheral blood or derived from the bone marrow in cardiovascular and neoplastic diseases.

  19. The involvement of multipotential progenitor cells in Mooren's ulcer.

    PubMed

    Lee, In Gul; Ye, Juan; Kim, Jae Chan

    2005-06-30

    The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and a-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.

  20. Activin A expression regulates multipotency of mesenchymal progenitor cells

    PubMed Central

    2010-01-01

    Introduction Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional similarities of MPCs from different tissues and to identify specific factor(s) related to their multipotency. Methods For this purpose, we directly compared MPCs isolated from different adult tissues, including bone marrow, tonsil, muscle, and dental pulp. We first examined and compared proliferation rates, immunomodulatory properties, and multidifferentiation potential of these MPCs in vitro. Next, we specifically evaluated activin A expression profile and activin A:follistatin ratio in MPCs from the four sources. Results The multidifferentiation potential of the MPCs is correlated with activin A level and/or the activin A:follistatin ratio. Interestingly, by siRNA-mediated activin A knockdown, activin A was shown to be required for the chondrogenic and osteogenic differentiation of MPCs. These findings strongly suggest that activin A has a pivotal differentiation-related role in the early stages of chondrogenesis and osteogenesis while inhibiting adipogenesis of MPCs. Conclusions This comparative analysis of MPCs from different tissue sources also identifies bone marrow-derived MPCs as the most potent MPCs in terms of multilineage differentiation and immunosuppression, two key requirements in cell-based regenerative medicine. In addition, this study implicates the significance of activin A as a functional marker of MPC identity. PMID:20637060

  1. Lin28 sustains early renal progenitors and induces Wilms tumor.

    PubMed

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S; Zhu, Hao; Perez-Atayde, Antonio R; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q

    2014-05-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis.

  2. Prostate cancer stem/progenitor cells: identification, characterization, and implications.

    PubMed

    Tang, Dean G; Patrawala, Lubna; Calhoun, Tammy; Bhatia, Bobby; Choy, Grace; Schneider-Broussard, Robin; Jeter, Collene

    2007-01-01

    Several solid tumors have now been shown to contain stem cell-like cells called cancer stem cells (CSC). These cells, although generally rare, appear to be highly tumorigenic and may be the cells that drive tumor formation, maintain tumor homeostasis, and mediate tumor metastasis. In this Perspective, we first provide our insight on how a CSC should be defined. We then summarize our current knowledge of stem/progenitor cells in the normal human prostate (NHP), an organ highly susceptible to hyperproliferative diseases such as benign prostate hyperplasia (BPH) and prostate cancer (PCa). We further review the evidence that cultured PCa cells, xenograft prostate tumors, and patient tumors may contain stem/progenitor cells. Along with our discussion, we present several methodologies that can be potentially used to identify putative tumor-reinitiating CSC. Finally, we present a hypothetical model for the hierarchical organization of human PCa cells and discuss the implications of this model in helping understand prostate carcinogenesis and design novel diagnostic, prognostic, and therapeutic approaches.

  3. 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.

  4. A new multiple sex chromosome system X1X1X2X2/X1Y1X2Y2 in Siluriformes: cytogenetic characterization of Bunocephalus coracoideus (Aspredinidae).

    PubMed

    Ferreira, Milena; Garcia, Caroline; Matoso, Daniele Aparecida; de Jesus, Isac Silva; Feldberg, Eliana

    2016-10-01

    We analyzed one Bunocephalus coracoideus population from the Negro River basin using cytogenetic techniques. The results showed a diploid number of 42 chromosomes in both sexes, with the karyotypic formula 4m + 14sm + 24a and fundamental number (FN) = 60 for females and the formula 5m + 14sm + 23a and FN = 61 for males, constituting an X1X1X2X2/X1Y1X2Y2 multiple sex chromosome system. The constitutive heterochromatin is distributed in the pericentromeric regions of most of the chromosomes, except for the sex chromosomes, of which the X1, X2, and Y1 chromosomes were euchromatic and the Y2 chromosome was partially heterochromatic. 18S rDNA mapping confirmed the presence of nucleolar organizer regions on the short arms of the fifth chromosomal pair for both sexes. The 5S rDNA is present in the terminal regions of the short arms on the 2nd, 10th, and 12th pairs and on the X2 chromosome of both sexes; however, we observed variations in the presence of these ribosomal cistrons on the Y1 chromosome, on which the cistrons are pericentromeric, and on the Y2 chromosome, on which these cistrons are present in the terminal portions of the short and long arms. Telomeric sequences are located in the terminal regions of all of the chromosomes, particularly conspicuous blocks on the 10th and 12th pairs and internal telomeric sequences in the centromeric regions of the 1st, 6th, and 9th pairs for both sexes. This work describes an new sex chromosomes system for the Siluriformes and increases our genetic knowledge of the Aspredinidae family.

  5. Hand2 Function in Second Heart Field Progenitors is Essential for Cardiogenesis

    PubMed Central

    Tsuchihashi, Takatoshi; Maeda, Jun; Shin, Chong; Ivey, Kathryn N.; Black, Brian; Olson, Eric N.; Yamagishi, Hiroyuki; Srivastava, Deepak

    2011-01-01

    Cardiogenesis involves the contributions of multiple progenitor pools, including mesoderm-derived cardiac progenitors known as the first and second heart fields. Disruption of genetic pathways regulating individual subsets of cardiac progenitors likely underlies many forms of human cardiac malformations. Hand2 is a member of the basic helix loop helix (bHLH) family of transcription factors and is expressed in numerous cell lineages that contribute to the developing heart. However, the early embryonic lethality of Hand2-null mice has precluded lineage-specific study of its function in myocardial progenitors. Here, we generated and used a floxed allele of Hand2 to ablate its expression in specific cardiac cell populations at defined developmental points. We found that Hand2 expression within the mesoderm-derived second heart field progenitors was required for their survival and deletion in this domain recapitulated the complete Hand2-null phenotype. Loss of Hand2 at later stages of development and in restricted domains of the second heart field revealed a spectrum of cardiac anomalies resembling forms of human congenital heart disease. Molecular analyses of Hand2 mutant cells revealed several genes by which Hand2 may influence expansion of the cardiac progenitors. These findings demonstrate that Hand2 is essential for survival of second heart field progenitors and that the graded loss of Hand2 function in this cardiac progenitor pool can cause a spectrum of congenital heart malformation. PMID:21185281

  6. 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.

  7. 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

  8. FGF/EGF signaling regulates the renewal of early nephron progenitors during embryonic development.

    PubMed

    Brown, Aaron C; Adams, Derek; de Caestecker, Mark; Yang, Xuehui; Friesel, Robert; Oxburgh, Leif

    2011-12-01

    Recent studies indicate that nephron progenitor cells of the embryonic kidney are arranged in a series of compartments of an increasing state of differentiation. The earliest progenitor compartment, distinguished by expression of CITED1, possesses greater capacity for renewal and differentiation than later compartments. Signaling events governing progression of nephron progenitor cells through stages of increasing differentiation are poorly understood, and their elucidation will provide key insights into normal and dysregulated nephrogenesis, as well as into regenerative processes that follow kidney injury. In this study, we found that the mouse CITED1(+) progenitor compartment is maintained in response to receptor tyrosine kinase (RTK) ligands that activate both FGF and EGF receptors. This RTK signaling function is dependent on RAS and PI3K signaling but not ERK. In vivo, RAS inactivation by expression of sprouty 1 (Spry1) in CITED1(+) nephron progenitors results in loss of characteristic molecular marker expression and in increased death of progenitor cells. Lineage tracing shows that surviving Spry1-expressing progenitor cells are impaired in their subsequent epithelial differentiation, infrequently contributing to epithelial structures. These findings demonstrate that the survival and developmental potential of cells in the earliest embryonic nephron progenitor cell compartment are dependent on FGF/EGF signaling through RAS.

  9. Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window.

    PubMed

    Cras-Méneur, Corentin; Li, Lin; Kopan, Raphael; Permutt, M Alan

    2009-09-01

    Canonical Notch signaling is thought to control the endocrine/exocrine decision in early pancreatic progenitors. Later, RBP-Jkappa interacts with Ptf1a and E12 to promote acinar differentiation. To examine the involvement of Notch signaling in selecting specific endocrine lineages, we deregulated this pathway by targeted deletion of presenilin1 and presenilin2, the catalytic core of gamma-secretase, in Ngn3- or Pax6-expressing endocrine progenitors. Surprisingly, whereas Pax6(+) progenitors were irreversibly committed to the endocrine fate, we discovered that Ngn3(+) progenitors were bipotential in vivo and in vitro. When presenilin amounts are limiting, Ngn3(+) progenitors default to an acinar fate; subsequently, they expand rapidly to form the bulk of the exocrine pancreas. gamma-Secretase inhibitors confirmed that enzymatic activity was required to block acinar fate selection by Ngn3 progenitors. Genetic interactions identified Notch2 as the substrate, and suggest that gamma-secretase and Notch2 act in a noncanonical titration mechanism to sequester RBP-Jkappa away from Ptf1a, thus securing selection of the endocrine fate by Ngn3 progenitors. These results revise the current view of pancreatic cell fate hierarchy, establish that Ngn3 is not in itself sufficient to commit cells to the endocrine fate in the presence of Ptf1a, reveal a noncanonical action for Notch2 protein in endocrine cell fate selection, and demonstrate that acquisition of an endocrine fate by Ngn3(+) progenitors is gamma-secretase-dependent until Pax6 expression begins.

  10. Role of progenitor cell producing normal vagina by metaplasia in laparoscopic peritoneal vaginoplasty

    PubMed Central

    Mhatre, Pravin N.; Narkhede, Hemraj R.; Pawar, P. Amol; Mhatre, P. Jyoti; Kumar, Das Dhanjit

    2016-01-01

    CONTEXT: Host of vaginoplasty techniques have been described. None has been successful in developing normal vagina. Laparoscopic peritoneal vaginoplasty (LPV) is performed in Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS) culminating in normal vagina. AIMS: This study aims to confirm normal development of neovagina by anatomical and functional parameters of histology, cytology, and ultrasonography (USG) in LPV. To identify peritoneal progenitor cell by OCT4/SOX2 markers. To demonstrate the metaplastic conversion of peritoneum to neovagina and the progenitor cell concentration, distribution pattern. SETTINGS AND DESIGN: This is prospective experimental study, conducted at teaching hospital and private hospital. SUBJECTS AND METHODS: Fifteen women of MRKHS underwent LPV followed by histology, cytology, two-/three-dimensional USG of neovagina. Four women underwent peritoneal biopsy for identification of progenitor cells with OCT4/SOX2 markers. One patient underwent serial biopsies for 4 weeks for histology and progenitor cell immunohistochemistry. RESULTS: Normal vaginal histology and cytology were apparent. USG of neovagina showed normal appearance and blood flow. Two peritoneal samples confirmed the presence of progenitor cells. Serial biopsies demonstrated the epithelial change from single to multilayer with stromal compaction and neoangiogenesis. The progenitor cells concentration and different distribution patterns were described using SOX2/OCT4 markers. CONCLUSIONS: We have shown successful peritoneal metaplastic conversion to normal vagina in LPV. The progenitor cell was identified in normal peritoneum using SOX2/OCT4 markers. The progenitor cell concentration and pattern were demonstrated at various stages of neovaginal development. PMID:28216908

  11. A  Complex Code of Extrinsic Influences on Cortical Progenitor Cells of Higher Mammals.

    PubMed

    Reillo, Isabel; de Juan Romero, Camino; Cárdenas, Adrián; Clascá, Francisco; Martínez-Martinez, Maria Ángeles; Borrell, Víctor

    2017-09-01

    Development of the cerebral cortex depends critically on the regulation of progenitor cell proliferation and fate. Cortical progenitor cells are remarkably diverse with regard to their morphology as well as laminar and areal position. Extrinsic factors, such as thalamic axons, have been proposed to play key roles in progenitor cell regulation, but the diversity, extent and timing of interactions between extrinsic elements and each class of cortical progenitor cell in higher mammals remain undefined. Here we use the ferret to demonstrate the existence of a complex set of extrinsic elements that may interact, alone or in combination, with subpopulations of progenitor cells, defining a code of extrinsic influences. This code and its complexity vary significantly between developmental stages, layer of residence and morphology of progenitor cells. By analyzing the spatial-temporal overlap of progenitor cell subtypes with neuronal and axonal populations, we show that multiple sets of migrating neurons and axon tracts overlap extensively with subdivisions of the Subventricular Zones, in an exquisite lamina-specific pattern. Our findings provide a framework for understanding the feedback influence of both intra- and extra-cortical elements onto progenitor cells to modulate their dynamics and fate decisions in gyrencephalic brains. © The Author 2017. Published by Oxford University Press.

  12. Identification and Characterization of Aortic Valve Mesenchymal Progenitor Cells with Robust Osteogenic Calcification Potential

    PubMed Central

    Chen, Jan-Hung; Yip, Cindy Ying Yin; Sone, Eli D.; Simmons, Craig A.

    2009-01-01

    Advanced valvular lesions often contain ectopic mesenchymal tissues, which may be elaborated by an unidentified multipotent progenitor subpopulation within the valve interstitium. The identity, frequency, and differentiation potential of the putative progenitor subpopulation are unknown. The objectives of this study were to determine whether valve interstitial cells (VICs) contain a subpopulation of multipotent mesenchymal progenitor cells, to measure the frequencies of the mesenchymal progenitors and osteoprogenitors, and to characterize the osteoprogenitor subpopulation because of its potential role in calcific aortic valve disease. The multilineage potential of freshly isolated and subcultured porcine aortic VICs was tested in vitro. Progenitor frequencies and self-renewal capacity were determined by limiting dilution and colony-forming unit assays. VICs were inducible to osteogenic, adipogenic, chondrogenic, and myofibrogenic lineages. Osteogenic differentiation was also observed in situ in sclerotic porcine leaflets. Primary VICs had strikingly high frequencies of mesenchymal progenitors (48.0 ± 5.7%) and osteoprogenitors (44.1 ± 12.0%). High frequencies were maintained for up to six population doublings, but decreased after nine population doublings to 28.2 ± 9.9% and 5.8 ± 1.3%, for mesenchymal progenitors and osteoprogenitors, respectively. We further identified the putative osteoprogenitor subpopulation as morphologically distinct cells that occur at high frequency, self-renew, and elaborate bone matrix from single cells. These findings demonstrate that the aortic valve is rich in a mesenchyma l progenitor cell population that has strong potential to contribute to valve calcification. PMID:19218344

  13. Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors

    PubMed Central

    Ninov, Nikolay; Borius, Maxim; Stainier, Didier Y. R.

    2012-01-01

    Genetic studies have implicated Notch signaling in the maintenance of pancreatic progenitors. However, how Notch signaling regulates the quiescent, proliferative or differentiation behaviors of pancreatic progenitors at the single-cell level remains unclear. Here, using single-cell genetic analyses and a new transgenic system that allows dynamic assessment of Notch signaling, we address how discrete levels of Notch signaling regulate the behavior of endocrine progenitors in the zebrafish intrapancreatic duct. We find that these progenitors experience different levels of Notch signaling, which in turn regulate distinct cellular outcomes. High levels of Notch signaling induce quiescence, whereas lower levels promote progenitor amplification. The sustained downregulation of Notch signaling triggers a multistep process that includes cell cycle entry and progenitor amplification prior to endocrine differentiation. Importantly, progenitor amplification and differentiation can be uncoupled by modulating the duration and/or extent of Notch signaling downregulation, indicating that these processes are triggered by distinct levels of Notch signaling. These data show that different levels of Notch signaling drive distinct behaviors in a progenitor population. PMID:22492351

  14. Regulation of development of rat stem and progenitor Leydig cells by activin.

    PubMed

    Li, L; Wang, Y; Li, X; Liu, S; Wang, G; Lin, H; Zhu, Q; Guo, J; Chen, H; Ge, H-S; Ge, R-S

    2017-01-01

    Stem Leydig cells have been demonstrated to differentiate into adult Leydig cells via intermediate stages of progenitor and immature Leydig cells. However, the exact regulatory mechanisms are unclear. We hypothesized that the development of stem or progenitor Leydig cells depends upon locally produced growth factors. Microarray analysis revealed that the expression levels of activin type I receptor (Acvr1) and activin A receptor type II-like 1 (Acvrl1) were stem > progenitor = immature = adult Leydig cells. This indicates that their ligand activin might play an important role in stem and progenitor Leydig cell proliferation and differentiation. When seminiferous tubules were incubated with 1 or 10 ng/mL activin A for 3 days, it concentration-dependently increased EdU incorporation into stem Leydig cells by up to 20-fold. When progenitor Leydig cells were incubated with 1 or 10 ng/mL activin A for 2 days, it concentration-dependently increased (3) H-thymidine incorporation into progenitor Leydig cells by up to 200%. Real-time PCR analysis showed that activin A primarily increased Pcna expression but reduced Star, Hsd3b1, and Cyp17a1 expression levels. Activin A also significantly inhibited the basal and luteinizing hormone-stimulated androgen production. In conclusion, activin A primarily stimulates the proliferation of stem and progenitor Leydig cells, but inhibits the differentiation of stem and progenitor Leydig cells into the Leydig cell lineage in rat testis.

  15. Characterization of adipocytes derived from fibro/adipogenic progenitors resident in human skeletal muscle

    PubMed Central

    Arrighi, N; Moratal, C; Clément, N; Giorgetti-Peraldi, S; Peraldi, P; Loubat, A; Kurzenne, J-Y; Dani, C; Chopard, A; Dechesne, C A

    2015-01-01

    A population of fibro/adipogenic but non-myogenic progenitors located between skeletal muscle fibers was recently discovered. The aim of this study was to determine the extent to which these progenitors differentiate into fully functional adipocytes. The characterization of muscle progenitor-derived adipocytes is a central issue in understanding muscle homeostasis. They are considered as being the cellular origin of intermuscular adipose tissue that develops in several pathophysiological situations. Here fibro/adipogenic progenitors were isolated from a panel of 15 human muscle biopsies on the basis of the specific cell-surface immunophenotype CD15+/PDGFRα+CD56−. This allowed investigations of their differentiation into adipocytes and the cellular functions of terminally differentiated adipocytes. Adipogenic differentiation was found to be regulated by the same effectors as those regulating differentiation of progenitors derived from white subcutaneous adipose tissue. Similarly, basic adipocyte functions, such as triglyceride synthesis and lipolysis occurred at levels similar to those observed with subcutaneous adipose tissue progenitor-derived adipocytes. However, muscle progenitor-derived adipocytes were found to be insensitive to insulin-induced glucose uptake, in association with the impairment of phosphorylation of key insulin-signaling effectors. Our findings indicate that muscle adipogenic progenitors give rise to bona fide white adipocytes that have the unexpected feature of being insulin-resistant. PMID:25906156

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

    PubMed

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

    2010-04-01

    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.

  17. Growth factor- and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization

    PubMed Central

    Peplow, Philip V.

    2014-01-01

    Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes specific growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endothelial progenitor cells migrate and home to specific sites following ischemic stroke via growth factor/cytokine gradients. Some growth factors are less stable under acidic conditions of tissue ischemia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovascularization following ischemic stroke. PMID:25317152

  18. 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

  19. 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.

  20. RBP-J (Rbpsuh) is essential to maintain muscle progenitor cells and to generate satellite cells.

    PubMed

    Vasyutina, Elena; Lenhard, Diana C; Wende, Hagen; Erdmann, Bettina; Epstein, Jonathan A; Birchmeier, Carmen

    2007-03-13

    In the developing muscle, a pool of myogenic progenitor cells is formed and maintained. These resident progenitors provide a source of cells for muscle growth in development and generate satellite cells in the perinatal period. By the use of conditional mutagenesis in mice, we demonstrate here that the major mediator of Notch signaling, the transcription factor RBP-J, is essential to maintain this pool of progenitor cells in an undifferentiated state. In the absence of RBP-J, these cells undergo uncontrolled myogenic differentiation, leading to a depletion of the progenitor pool. This results in a lack of muscle growth in development and severe muscle hypotrophy. In addition, satellite cells are not formed late in fetal development in conditional RBP-J mutant mice. We conclude that RBP-J is required in the developing muscle to set aside proliferating progenitors and satellite cells.

  1. Diabetes Irreversibly Depletes Bone Marrow–Derived Mesenchymal Progenitor Cell Subpopulations

    PubMed Central

    Januszyk, Michael; Sorkin, Michael; Glotzbach, Jason P.; Vial, Ivan N.; Maan, Zeshaan N.; Rennert, Robert C.; Duscher, Dominik; Thangarajah, Hariharan; Longaker, Michael T.; Butte, Atul J.

    2014-01-01

    Diabetic vascular pathology is largely attributable to impairments in tissue recovery from hypoxia. Circulating progenitor cells have been postulated to play a role in ischemic recovery, and deficiencies in these cells have been well described in diabetic patients. Here, we examine bone marrow–derived mesenchymal progenitor cells (BM-MPCs) that have previously been shown to be important for new blood vessel formation and demonstrate significant deficits in the context of diabetes. Further, we determine that this dysfunction is attributable to intrinsic defects in diabetic BM-MPCs that are not correctable by restoring glucose homeostasis. We identify two transcriptionally distinct subpopulations that are selectively depleted by both type 1 and type 2 diabetes, and these subpopulations have provasculogenic expression profiles, suggesting that they are vascular progenitor cells. These results suggest that the clinically observed deficits in progenitor cells may be attributable to selective and irreversible depletion of progenitor cell subsets in patients with diabetes. PMID:24740572

  2. 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

  3. 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

  4. 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

    2016-04-12

    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.

  5. 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

  6. 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

    2016-06-01

    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.

  7. Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors

    PubMed Central

    Kwon, Chulan; Arnold, Joshua; Hsiao, Edward C.; Taketo, Makoto M.; Conklin, Bruce R.; Srivastava, Deepak

    2007-01-01

    Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Wnt pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Wnt ligands are thought to negatively regulate cardiomyogenesis in several species. However, the cell-autonomous role of canonical Wnt signaling within precardiac mesoderm, through its obligatory transcriptional mediator, β-catenin, is unknown. Using tissue-specific in vivo genetic manipulation, we found that β-catenin is required for development of cardiac progenitors and is a positive regulator of proliferative expansion of such progenitor cells. At discrete windows of development in embryonic stem cells, activation of canonical Wnt signaling promoted expansion of cardiac progenitors after initial commitment and was required for cardiac differentiation. Together, these data provide in vivo and in vitro evidence that canonical Wnt signaling promotes the expansion of cardiac progenitors and differentiation of cardiomyocytes. PMID:17576928

  8. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development.

    PubMed

    Azim, Eiman; Jabaudon, Denis; Fame, Ryann M; Macklis, Jeffrey D

    2009-10-01

    The neuronal diversity of the CNS emerges largely from controlled spatial and temporal segregation of cell type-specific molecular regulators. We found that the transcription factor SOX6 controls the molecular segregation of dorsal (pallial) from ventral (subpallial) telencephalic progenitors and the differentiation of cortical interneurons, regulating forebrain progenitor and interneuron heterogeneity. During corticogenesis in mice, SOX6 and SOX5 were largely mutually exclusively expressed in pallial and subpallial progenitors, respectively, and remained mutually exclusive in a reverse pattern in postmitotic neuronal progeny. Loss of SOX6 from pallial progenitors caused their inappropriate expression of normally subpallium-restricted developmental controls, conferring mixed dorsal-ventral identity. In postmitotic cortical interneurons, loss of SOX6 disrupted the differentiation and diversity of cortical interneuron subtypes, analogous to SOX5 control over cortical projection neuron development. These data indicate that SOX6 is a central regulator of both progenitor and cortical interneuron diversity during neocortical development.

  9. Yap controls stem/progenitor cell proliferation in the mouse postnatal epidermis.

    PubMed

    Beverdam, Annemiek; Claxton, Christina; Zhang, Xiaomeng; James, Gregory; Harvey, Kieran F; Key, Brian

    2013-06-01

    Tissue renewal is an ongoing process in the epithelium of the skin. We have begun to examine the genetic mechanisms that control stem/progenitor cell activation in the postnatal epidermis. The conserved Hippo pathway regulates stem cell turnover in arthropods through to vertebrates. Here we show that its downstream effector, yes-associated protein (YAP), is active in the stem/progenitor cells of the postnatal epidermis. Overexpression of a C-terminally truncated YAP mutant in the basal epidermis of transgenic mice caused marked expansion of epidermal stem/progenitor cell populations. Our data suggest that the C-terminus of YAP controls the balance between stem/progenitor cell proliferation and differentiation in the postnatal interfollicular epidermis. We conclude that YAP functions as a molecular switch of stem/progenitor cell activation in the epidermis. Moreover, our results highlight YAP as a possible therapeutic target for diseases such as skin cancer, psoriasis, and epidermolysis bullosa.

  10. A Twist2-dependent progenitor cell contributes to adult skeletal muscle.

    PubMed

    Liu, Ning; Garry, Glynnis A; Li, Stephen; Bezprozvannaya, Svetlana; Sanchez-Ortiz, Efrain; Chen, Beibei; Shelton, John M; Jaichander, Priscilla; Bassel-Duby, Rhonda; Olson, Eric N

    2017-03-01

    Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells. Tw2(+) progenitors contribute specifically to type IIb/x myofibres during adulthood and muscle regeneration, and their genetic ablation causes wasting of type IIb myofibres. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that extinguish Tw2 expression. Tw2-expressing myogenic progenitors represent a previously unrecognized, fibre-type-specific stem cell involved in postnatal muscle growth and regeneration.

  11. Roles of nonmyogenic mesenchymal progenitors in pathogenesis and regeneration of skeletal muscle

    PubMed Central

    Uezumi, Akiyoshi; Ikemoto-Uezumi, Madoka; Tsuchida, Kunihiro

    2014-01-01

    Adult skeletal muscle possesses a remarkable regenerative ability that is dependent on satellite cells. However, skeletal muscle is replaced by fatty and fibrous connective tissue in several pathological conditions. Fatty and fibrous connective tissue becomes a major cause of muscle weakness and leads to further impairment of muscle function. Because the occurrence of fatty and fibrous connective tissue is usually associated with severe destruction of muscle, the idea that dysregulation of the fate switch in satellite cells may underlie this pathological change has emerged. However, recent studies identified nonmyogenic mesenchymal progenitors in skeletal muscle and revealed that fatty and fibrous connective tissue originates from these progenitors. Later, these progenitors were also demonstrated to be the major contributor to heterotopic ossification in skeletal muscle. Because nonmyogenic mesenchymal progenitors represent a distinct cell population from satellite cells, targeting these progenitors could be an ideal therapeutic strategy that specifically prevents pathological changes of skeletal muscle, while preserving satellite cell-dependent regeneration. In addition to their roles in pathogenesis of skeletal muscle, nonmyogenic mesenchymal progenitors may play a vital role in muscle regeneration by regulating satellite cell behavior. Conversely, muscle cells appear to regulate behavior of nonmyogenic mesenchymal progenitors. Thus, these cells regulate each other reciprocally and a proper balance between them is a key determinant of muscle integrity. Furthermore, nonmyogenic mesenchymal progenitors have been shown to maintain muscle mass in a steady homeostatic condition. Understanding the nature of nonmyogenic mesenchymal progenitors will provide valuable insight into the pathophysiology of skeletal muscle. In this review, we focus on nonmyogenic mesenchymal progenitors and discuss their roles in muscle pathogenesis, regeneration, and homeostasis. PMID

  12. 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

  13. 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.

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

    PubMed Central

    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 56Fe 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 56Fe 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 56Fe. 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

  15. FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney.

    PubMed

    Fetting, Jennifer L; Guay, Justin A; Karolak, Michele J; Iozzo, Renato V; Adams, Derek C; Maridas, David E; Brown, Aaron C; Oxburgh, Leif

    2014-01-01

    Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. Foxd1 is required during kidney development and its inactivation results in failure of nephron progenitor cell differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron progenitor cells, suggesting an essential role for the progenitor cell niche in nephrogenesis. To better understand how cortical interstitial cells in general, and FOXD1 in particular, influence the progenitor cell niche, we examined the differentiation states of two progenitor cell subtypes in Foxd1(-/-) tissue. We found that although nephron progenitor cells are retained in a primitive CITED1-expressing compartment, cortical interstitial cells prematurely differentiate. To identify pathways regulated by FOXD1, we screened for target genes by comparison of Foxd1 null and wild-type tissues. We found that the gene encoding the small leucine-rich proteoglycan decorin (DCN) is repressed by FOXD1 in cortical interstitial cells, and we show that compound genetic inactivation of Dcn partially rescues the failure of progenitor cell differentiation in the Foxd1 null. We demonstrate that DCN antagonizes BMP/SMAD signaling, which is required for the transition of CITED1-expressing nephron progenitor cells to a state that is primed for WNT-induced epithelial differentiation. On the basis of these studies, we propose a mechanism for progenitor cell retention in the Foxd1 null in which misexpressed DCN produced by prematurely differentiated interstitial cells accumulates in the extracellular matrix, inhibiting BMP7-mediated transition of nephron progenitor cells to a compartment in which they can respond to epithelial induction signals.

  16. The effect of hematopoietic progenitor cells' temperature on cardiac arrhythmias in patients given peripheral blood progenitor cells.

    PubMed

    Donmez, Ayhan; Zoghi, Mehdi; Cagirgan, Seckin; Acarlar, Ceylan; Tombuloglu, Murat

    2006-06-01

    Infusion of cryopreserved and non-cryopreserved hematopoietic progenitor cells (HPC) is associated with a broad variety of symptoms. In this study, we have investigated infusion-related toxicity regarding temperature of cryopreserved autologous peripheral blood progenitor cells (PBPCs) transplanted in 31 and allogeneic non-cryopreserved PBPCs in 4 patients receiving high dose chemotherapy and stem cells transplantation for hematological malignancies. A 24h ECG-Holter recording system was used to obtain cardiac arrhythmias. Two milliliters HPC were collected from entrance site of venous access to evaluate the temperature of infused HPC. We have detected arrhythmias in 17 (48.58%) of our patients before, during and after infusion. Median temperature of the infusat was 21 degrees C (18-28.2). Arrhythmias during infusion were detected in 8 (22.85%) patients. The temperatures of infused HPCs were not statistically different in group with and without arrhythmias as 22 degrees C and 21 degrees C, respectively (P>0.05). And also, volume, contents [dimethylsulphoxide (DMSO), red blood cells (RBC), platelet (PLT), and total nucleated cell (TNC)] of product, and rate of infusion speed did not have any effect on arrhythmias. As a result of this study, we have concluded that the temperature of HPC does not cause any systemic hypothermia and does not have any relation to arrhythmias detected during infusion.

  17. Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

    PubMed Central

    TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA

    2013-01-01

    Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in

  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. Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome.

    PubMed

    Timeus, Fabio; Crescenzio, Nicoletta; Baldassarre, Giuseppina; Doria, Alessandra; Vallero, Stefano; Foglia, Luiselda; Pagliano, Sara; Rossi, Cesare; Silengo, Margherita Cirillo; Ramenghi, Ugo; Fagioli, Franca; Cordero di Montezemolo, Luca; Ferrero, Giovanni Battista

    2013-08-01

    Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis>1,000/µl. Ten out of the 27 NS patients showed monocytosis>1,000/µl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/µl; range, 44-232) with a low rate of apoptosis (median, 2.1%; range, 0.4-12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/µl, 205.7; range, 58-1374; median apoptotic rate, 1.4%; range, 0.2-2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/µl, 4.9; range, 1.3-17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the

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

    PubMed

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

    2015-03-09

    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.

  1. Fibro/Adipogenic Progenitors (FAPs): Isolation by FACS and Culture.

    PubMed

    Low, Marcela; Eisner, Christine; Rossi, Fabio

    2017-01-01

    Fibro/adipogenic progenitors (FAPs ) are tissue-resident mesenchymal stromal cells (MSCs). Current literature supports a role for these cells in the homeostasis and repair of multiple tissues suggesting that FAPs may have extensive therapeutic potential in the treatment of numerous diseases. In this context, it is crucial to establish efficient and reproducible procedures to purify FAP populations from various tissues. Here, we describe a protocol for the isolation and cell culture of FAPs from murine skeletal muscle using fluorescence -activated cell sorting (FACS), which is particularly useful for experiments where high cell purity is an essential requirement. Identification, isolation, and cell culture of FAPs represent powerful tools that will help us to understand the role of these cells in different conditions and facilitate the development of safe and effective new treatments for diseases.

  2. Tbx16 regulates hox gene activation in mesodermal progenitor cells

    PubMed Central

    Payumo, Alexander Y.; McQuade, Lindsey E.; Walker, Whitney J.; Yamazoe, Sayumi; Chen, James K.

    2016-01-01

    The transcription factor T-box 16 (Tbx16/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. The mechanisms by which Tbx16 controls mesoderm patterning have remained enigmatic, and we describe here the application of photoactivatable morpholino oligonucleotides to determine the Tbx16 transcriptome in MPCs. We identify 124 Tbx16-regulated genes that are expressed in zebrafish gastrulae, including several developmental signaling proteins and regulators of gastrulation, myogenesis, and somitogenesis. Unexpectedly, we observe that loss of Tbx16 function precociously activates posterior hox genes in MPCs, and overexpression of a single posterior hox gene is 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

  3. Mass Loss From SN Ib/c Progenitors

    NASA Astrophysics Data System (ADS)

    Young, P. A.; Arnett, D.

    2002-12-01

    We examine mass loss in possible SN Ib/c progenitor stars. Super-Eddington luminosities are seen at the base of the hydrogen envelope in 1-D stellar evolution simulations for stars exceeding approximately 40 solar masses. The resulting hydrodynamic instabilities are modelled in multi-dimensional numerical simulations as a possible mechanism for the catastrophic mass loss seen in luminous blue variables (LBVs) and the complete envelope loss leading to a Wolf-Rayet morphology. The evolution of the ejected mass is followed, as structure produced by instabilities in the outflowing material may have an important and observable effect on the subsequent evolution of a supernova remnant. This work was supported by a grant from the D.O.E. and a subcontract from the ASCI FLASH Center at the University of Chicago.

  4. Endothelial Progenitor Cells=EPC=Elemental Pernicious Complexity

    PubMed Central

    Ushio-Fukai, Masuko

    2011-01-01

    Abstract Endothelial progenitor cells (EPCs) represent a heterogeneous population of cells with a pro-angiogenic potential that are derived not only from bone marrow but also from other tissues. Depending on the model and cell type used, the pro-angiogenic effect is a consequence of direct vascular integration, the paracrine release of growth factors and cytokines, or complex interactions with other cellular components like monocytes or platelets. The pro-angiogenic potential of EPCs is dependent on the particular type of EPC studied and modulated by the risk and life style factors of the patient as well as by local factors determining the homing to diseased tissue and the EPC proteome. In this Forum on EPCs these aspects will be covered in individual review articles, which are accompanied by two original research studies on the role of NADPH oxidases for EPC mobilization and the impact of organic nitrates on EPCs. Antioxid. Redox Signal. 15, 911–914. PMID:21128729

  5. SWI/SNF in cardiac progenitor cell differentiation

    PubMed Central

    Lei, Ienglam; Liu, Liu; Sham, Mai Har; Wang, Zhong

    2014-01-01

    Cardiogenesis requires proper specification, proliferation, and differentiation of cardiac progenitor cells (CPCs). The differentiation of CPCs to specific cardiac cell types is likely guided by a comprehensive network comprised of cardiac transcription factors and epigenetic complexes. In this review, we describe how the ATP-dependent chromatin remodeling SWI/SNF complexes work synergistically with transcription and epigenetic factors to direct specific cardiac gene expression during CPC differentiation. Furthermore, we discuss how SWI/SNF may prime chromatin for cardiac gene expression at a genome-wide level. A detailed understanding of SWI/SNF-mediated CPC differentiation will provide important insight into the etiology of cardica defects and help design novel therapies for heart disease. PMID:23606236

  6. Coronary Artery Development: Progenitor Cells and Differentiation Pathways

    PubMed Central

    Sharma, Bikram; Chang, Andrew; Red-Horse, Kristy

    2017-01-01

    Coronary artery disease (CAD) is the number one cause of death worldwide and involves the accumulation of plaques within the artery wall that can occlude blood flow to the heart and cause myocardial infarction. The high mortality associated with CAD makes the development of medical interventions that repair and replace diseased arteries a high priority for the cardiovascular research community. Advancements in arterial regenerative medicine could benefit from a detailed understanding of coronary artery development during embryogenesis and of how these pathways might be reignited during disease. Recent research has advanced our knowledge on how the coronary vasculature is built and revealed unexpected features of progenitor cell deployment that may have implications for organogenesis in general. Here, we highlight these recent findings and discuss how they set the stage to interrogate developmental pathways during injury and disease. PMID:27959616

  7. [Autotransplantation of hematopoietic progenitor cells in multiple sclerosis].

    PubMed

    Fernández, J; Correale, J; Campestri, R; Koziner, B

    1999-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disease exhibiting great clinical variability. For control of its primary and secondary progressive variants, treatment has met with limited success. In recent years, increasing experience has been gained with the administration of high dose chemotherapy supported by the autologous infusion of hematopoietic progenitor cells (HPC), in some instances depleted of T cells. The European and International Registry of Hematopoietic Cell Transplantation for Autoimmune Diseases include 43 MS patients. BEAM was the most frequently used conditioning therapy. Treatment related mortality was 7%. The actuarial disease free survival and the overall projected survival at 38 months were 85% and 90% respectively. The inclusion of an increasing number of MS patients into these treatment programs and the growing submission of cases to the Registries will provide useful information to determine if the initial enthusiasm generated by this approach for the control of primary and secondary progressive forms of MS is justified.

  8. Possible binary star progenitor for SN1987A

    NASA Astrophysics Data System (ADS)

    White, Graeme L.; Malin, D. F.

    1987-05-01

    Accurate optical astrometry gives a position (B1950.0) for the Large Magellanic Cloud supernova, SN 1987A, relative to the FK 4 system as right ascension, RA = 05h 35min 49.95 s±0.039 s, declination δ = -69°17arcmin57.9arcsec±0.27arcsec. Differential astrometry carried out on prime-focus plates taken with the AAT indicates that the component, star 1, of Sanduleak's star Sk -69202 is within 0.05±0.13 arc s of the supernova. The authors conclude that the progenitor of SN 1987A was star 1 or a fainter binary companion.

  9. Glucocorticoid suppresses steroidogenesis in rat progenitor Leydig cells.

    PubMed

    Xiao, Ye-Chen; Huang, Ya-Dong; Hardy, Dianne O; Li, Xiao-Kun; Ge, Ren-Shan

    2010-01-01

    Glucocorticoid (GC) inhibits testosterone production in adult Leydig cells by the glucocorticoid receptor (GR). However, whether GC affects the development of Leydig cells is unclear. The goal of the present study is to investigate the effects of GC on steroidogenesis of rat progenitor Leydig cells (PLCs) in vitro. Dexamethasone (DEX) inhibited androsterone (AO) production in PLCs. The GR antagonist RU38486 reversed the DEX-induced inhibition of AO, whereas the mineralocorticoid receptor antagonist RU28318 did not. RU38486 also reversed DEX-induced reductions in steady-state mRNA levels of steroidogenic acute regulatory protein (Star) and 3β-hydroxysteroid dehydrogenase 1 (Hsd3b1). Steroidogenic acute regulatory protein (StAR) protein expression and 3β-hydroxysteroid dehydrogenase (3βHSD) enzyme activity were affected similarly. These results show that GCs inhibit steroidogenesis of PLCs by suppression of StAR and 3βHSD via a GR-mediated mechanism.

  10. Electrically Induced Calcium Handling in Cardiac Progenitor Cells

    PubMed Central

    Wagner, Mary B.

    2016-01-01

    For nearly a century, the heart was viewed as a terminally differentiated organ until the discovery of a resident population of cardiac stem cells known as cardiac progenitor cells (CPCs). It has been shown that the regenerative capacity of CPCs can be enhanced by ex vivo modification. Preconditioning CPCs could provide drastic improvements in cardiac structure and function; however, a systematic approach to determining a mechanistic basis for these modifications founded on the physiology of CPCs is lacking. We have identified a novel property of CPCs to respond to electrical stimulation by initiating intracellular Ca2+ oscillations. We used confocal microscopy and intracellular calcium imaging to determine the spatiotemporal properties of the Ca2+ signal and the key proteins involved in this process using pharmacological inhibition and confocal Ca2+ imaging. Our results provide valuable insights into mechanisms to enhance the therapeutic potential in stem cells and further our understanding of human CPC physiology. PMID:27818693

  11. Hepatic progenitor cells of biliary origin with liver repopulation capacity

    PubMed Central

    Boulter, Luke; Tsuchiya, Atsunori; Cole, Alicia M; Hay, Trevor; Guest, Rachel V; Wojtacha, Davina; Man, Tak Yung; Mackinnon, Alison; Ridgway, Rachel A; Kendall, Timothy; Williams, Michael J; Jamieson, Thomas; Raven, Alex; Hay, David C; Iredale, John P; Clarke, Alan R; Sansom, Owen J; Forbes, Stuart J

    2015-01-01

    Summary Hepatocytes and cholangiocytes self renew following liver injury. Following severe injury hepatocytes are increasingly senescent, whether Hepatic Progenitor Cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where Mdm2 is inducibly deleted in over 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease. PMID:26192438

  12. Migrating Oligodendrocyte Progenitor Cells Swell Prior to Soma Dislocation

    PubMed Central

    Happel, Patrick; Möller, Kerstin; Schwering, Nina K.; Dietzel, Irmgard D.

    2013-01-01

    The migration of oligodendrocyte progenitor cells (OPCs) to the white matter is an indispensable requirement for an intact brain function. The mechanism of cell migration in general is not yet completely understood. Nevertheless, evidence is accumulating that besides the coordinated rearrangement of the cytoskeleton, a finetuned interplay of ion and water fluxes across the cell membrane is essential for cell migration. One part of a general hypothesis is that a local volume increase towards the direction of movement triggers a mechano-activated calcium influx that regulates various procedures at the rear end of a migrating cell. Here, we investigated cell volume changes of migrating OPCs using scanning ion conductance microscopy. We found that during accelerated migration OPCs undergo an increase in the frontal cell body volume. These findings are supplemented with time lapse calcium imaging data that hint an increase in calcium content the frontal part of the cell soma. PMID:23657670

  13. 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.

  14. Neural stem/progenitor cells in Alzheimer's disease.

    PubMed

    Tincer, Gizem; Mashkaryan, Violeta; Bhattarai, Prabesh; Kizil, Caghan

    2016-03-01

    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.

  15. 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

  16. Cell trafficking of endothelial progenitor cells in tumor progression.

    PubMed

    de la Puente, Pilar; Muz, Barbara; Azab, Feda; Azab, Abdel Kareem

    2013-07-01

    Blood vessel formation plays an essential role in many physiologic and pathologic processes, including normal tissue growth and healing, as well as tumor progression. Endothelial progenitor cells (EPC) are a subtype of stem cells with high proliferative potential that are capable of differentiating into mature endothelial cells, thus contributing to neovascularization in tumors. In response to tumor-secreted cytokines, EPCs mobilize from the bone marrow to the peripheral blood, home to the tumor site, and differentiate to mature endothelial cells and secrete proangiogenic factors to facilitate vascularization of tumors. In this review, we summarize the expression of surface markers, cytokines, receptors, adhesion molecules, proteases, and cell signaling mechanisms involved in the different steps (mobilization, homing, and differentiation) of EPC trafficking from the bone marrow to the tumor site. Understanding the biologic mechanisms of EPC cell trafficking opens a window for new therapeutic targets in cancer.

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

    PubMed

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

    2015-08-05

    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.

  18. 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.

  19. Spontaneous Calcium Oscillations Regulate Human Cardiac Progenitor Cell Growth

    PubMed Central

    Ferreira-Martins, João; Rondon-Clavo, Carlos; Tugal, Derin; Korn, Justin A; Rizzi, Roberto; Padin-Iruegas, Maria Elena; Ottolenghi, Sergio; De Angelis, Antonella; Urbanek, Konrad; Iwata, Noriko; D’Amario, Domenico; Hosoda, Toru; Leri, Annarosa; Kajstura, Jan; Anversa, Piero; Rota, Marcello

    2009-01-01

    Rationale The adult heart possesses a pool of progenitor cells stored in myocardial niches but the mechanisms involved in the activation of this cell compartment are currently unknown. Objective Ca2+ promotes cell growth raising the possibility that changes in intracellular Ca2+ initiate division of c-kit-positive human cardiac progenitor cells (hCPCs) and determine their fate. Methods and Results Ca2+ oscillations were identified in hCPCs and these events occurred independently from coupling with cardiomyocytes or the presence of extracellular Ca2+. These findings were confirmed in the heart of transgenic mice in which EGFP was under the control of the c-kit-promoter. Ca2+ oscillations in hCPCs were regulated by the release of Ca2+ from the ER through activation of inositol 1,4,5-triphosphate receptors (IP3Rs) and the re-uptake of Ca2+ by the sarco/endoplasmic reticulum Ca2+ pump (SERCA). IP3Rs and SERCA were highly expressed in hCPCs while ryanodine receptors were not detected. Although Na+-Ca2+ exchanger, store-operated Ca2+-channels and plasma membrane Ca2+-pump were present and functional in hCPCs, they had no direct effects on Ca2+ oscillations. Conversely, Ca2+ oscillations and their frequency markedly increased with ATP and histamine which activated purinoceptors and histamine-1 receptors highly expressed in hCPCs. Importantly, Ca2+ oscillations in hCPCs were coupled with the entry of cells into the cell cycle and BrdUrd incorporation. Induction of Ca2+ oscillations in hCPCs prior to their intramyocardial delivery to infarcted hearts was associated with enhanced engraftment and expansion of these cells promoting the generation of a large myocyte progeny. Conclusion IP3R-mediated Ca2+ mobilization control hCPC growth and their regenerative potential. PMID:19745162

  20. Uncaria tomentosa stimulates the proliferation of myeloid progenitor cells.

    PubMed

    Farias, Iria; do Carmo Araújo, Maria; Zimmermann, Estevan Sonego; Dalmora, Sergio Luiz; Benedetti, Aloisio Luiz; Alvarez-Silva, Marcio; Asbahr, Ana Carolina Cavazzin; Bertol, Gustavo; Farias, Júlia; Schetinger, Maria Rosa Chitolina

    2011-09-01

    The Asháninkas, indigenous people of Peru, use cat's claw (Uncaria tomentosa) to restore health. Uncaria tomentosa has antioxidant activity and works as an agent to repair DNA damage. It causes different effects on cell proliferation depending on the cell type involved; specifically, it can stimulate the proliferation of myeloid progenitors and cause apoptosis of neoplastic cells. Neutropenia is the most common collateral effect of chemotherapy. For patients undergoing cancer treatment, the administration of a drug that stimulates the proliferation of healthy hematopoietic tissue cells is very desirable. It is important to assess the acute effects of Uncaria tomentosa on granulocyte-macrophage colony-forming cells (CFU-GM) and in the recovery of neutrophils after chemotherapy-induced neutropenia, by establishing the correlation with filgrastim (rhG-CSF) treatment to evaluate its possible use in clinical oncology. The in vivo assay was performed in ifosfamide-treated mice receiving oral doses of 5 and 15 mg of Uncaria tomentosa and intraperitoneal doses of 3 and 9 μg of filgrastim, respectively, for four days. Colony-forming cell (CFC) assays were performed with human hematopoietic stem/precursor cells (hHSPCs) obtained from umbilical cord blood (UCB). Bioassays showed that treatment with Uncaria tomentosa significantly increased the neutrophil count, and a potency of 85.2% was calculated in relation to filgrastim at the corresponding doses tested. An in vitro CFC assay showed an increase in CFU-GM size and mixed colonies (CFU-GEMM) size at the final concentrations of 100 and 200 μg extract/mL. At the tested doses, Uncaria tomentosa had a positive effect on myeloid progenitor number and is promising for use with chemotherapy to minimize the adverse effects of this treatment. These results support the belief of the Asháninkas, who have classified Uncaria tomentosa as a 'powerful plant'. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Pak2 regulates hematopoietic progenitor cell proliferation, survival and differentiation

    PubMed Central

    Zeng, Yi; Broxmeyer, Hal E.; Staser, Karl; Chitteti, Brahmananda Reddy; Park, Su-Jung; Hahn, Seongmin; Cooper, Scott; Sun, Zejin; Jiang, Li; Yang, XianLin; Yuan, Jin; Kosoff, Rachelle; Sandusky, George; Srour, Edward F.; Chernoff, Jonathan; Clapp, Wade

    2015-01-01

    p21-activated kinase 2 (Pak2), a serine/threonine kinase, has been previously shown to be essential for hematopoietic stem cell (HSC) engraftment. However, Pak2 modulation of long-term hematopoiesis and lineage commitment remain unreported. Utilizing a conditional Pak2 knock out (KO) mouse model, we found that disruption of Pak2 in HSCs induced profound leukopenia and a mild macrocytic anemia. Although loss of Pak2 in HSCs leads to less efficient short- and long-term competitive hematopoiesis than wild type (WT) cells, it does not affect HSC self-renewal per se. Pak2 disruption decreased the survival and proliferation of multi-cytokine stimulated immature progenitors. Loss of Pak2 skewed lineage differentiation toward granulocytopoiesis and monocytopoiesis in mice as evidenced by 1) a three to six-fold increase in the percentage of peripheral blood granulocytes and a significant increase in the percentage of granulocyte-monocyte progenitors (GMPs) in mice transplanted with Pak2-disrupted BM; 2) Pak2-disrupted BM and c-kit+ cells yielded higher numbers of more mature subsets of granulocyte-monocyte colonies and polymophonuclear neutrophils (PMNs), respectively, when cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF). Pak2 disruption resulted respectively in decreased and increased gene expression of transcription factors JunB and c-Myc, which may suggest underlying mechanisms by which Pak2 regulates granulocyte-monocyte lineage commitment. Furthermore, Pak2 disruption led to 1) higher percentage of CD4+CD8+ double positive T cells and lower percentages of CD4+CD8− or CD4−CD8+ single positive T cells in thymus and 2) decreased numbers of mature B cells and increased numbers of Pre-Pro B cells in BM, suggesting defects in lymphopoiesis. PMID:25586960

  2. [Isolation and gene modification of amniotic fluid derived progenitor cells].

    PubMed

    Yang, Chenmin; Fan, Shuyue; Tang, Huixiang; Gong, Zhijuan; Gong, Xiuli; Ren, Zhaorui; Zeng, Fanyi

    2014-03-01

    We established methods to isolate human amniotic fluid-derived progenitor cells (hAFPCs), and analyze the ability of hAFPCs to secrete human coagulation factor IX (hFIX) after gene modification. The hAFPCs were manually isolated by selection for attachment to gelatin coated culture dish. hFIX cDNA was transfected into hAPFCs by using a lentiviral vector. The hFIX protein concentration and activity produced from hAFPCs were determined by enzyme-linked immunosorbent assay (ELISA) and clotting assay. The isolated spindle-shaped cells showed fibroblastoid morphology after three culture passages. The doubling time in culture was 39.05 hours. Immunocytochemistry staining of the fibroblast-like cells from amniotic fluid detected expression of stem cell markers such as SSEA4 and TRA1-60. Quantitative PCR analysis demonstrated the expression of NANOG, OCT4 and SOX2 mRNAs. Transfected hAFPCs could produce and secrete hFIX into the culture medium. The observed concentration of secreted hFIX was 20.37% +/- 2.77% two days after passage, with clotting activity of 16.42% +/- 1.78%. The amount of hFIX:Ag reached a plateau of 50.35% +/- 5.42%, with clotting activity 45.34% +/- 4.67%. In conclusion, this study established method to isolate and culture amniotic fluid progenitor cells. Transfected hAFPCs can produce hFIX at stable levels in vitro, and clotting activity increases with higher hFIX concentration. Genetically engineered hAFPC are a potential method for prenatal treatment of hemophilia B.

  3. Stem and progenitor cell alterations in myelodysplastic syndromes.

    PubMed

    Shastri, Aditi; Will, Britta; Steidl, Ulrich; Verma, Amit

    2017-03-23

    Recent studies have demonstrated that myelodysplastic syndromes (MDSs) arise from a small population of disease-initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in hematopoietic stem and progenitor cell (HSPC) numbers are also seen in a stage-specific manner in human MDS samples as well as in murine models of the disease. Overexpression of several markers such as interleukin-1 (IL-1) receptor accessory protein (IL1RAP), CD99, T-cell immunoglobulin mucin-3, and CD123 have begun to differentiate MDS HSPCs from healthy counterparts. Overactivation of innate immune components such as Toll-like receptors, IL-1 receptor-associated kinase/tumor necrosis factor receptor-associated factor-6, IL8/CXCR2, and IL1RAP signaling pathways has been demonstrated in MDS HSPCs and is being targeted therapeutically in preclinical and early clinical studies. Other dysregulated pathways such as signal transducer and activator of transcription 3, tyrosine kinase with immunoglobulinlike and EGF-like domains 1/angiopoietin-1, p21-activated kinase, microRNA 21, and transforming growth factor β are also being explored as therapeutic targets against MDS HSPCs. Taken together, these studies have demonstrated that MDS stem cells are functionally critical for the initiation, transformation, and relapse of disease and need to be targeted therapeutically for future curative strategies in MDSs.

  4. Functional genetic targeting of embryonic kidney progenitor cells ex vivo.

    PubMed

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

    2015-05-01

    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.

  5. 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.

  6. Presence of stem/progenitor cells in the rat penis.

    PubMed

    Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu; Wang, Jianwen; Wang, Lin; Li, Huixi; Wang, Guifang; Ning, Hongxiu; Lin, Ching-Shwun; Xin, Zhongcheng; Lue, Tom F

    2015-01-15

    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.

  7. Cartilage engineering from ovine umbilical cord blood mesenchymal progenitor cells.

    PubMed

    Fuchs, Julie R; Hannouche, Didier; Terada, Shinichi; Zand, Sarvenaz; Vacanti, Joseph P; Fauza, Dario O

    2005-08-01

    We aimed to determine whether three-dimensional (3D) cartilage could be engineered from umbilical cord blood (CB) cells and compare it with both engineered fetal cartilage and native tissue. Ovine mesenchymal progenitor cells were isolated from CB samples (n=4) harvested at 80-120 days of gestation by low-density fractionation, expanded, and seeded onto polyglycolic acid scaffolds. Constructs (n=28) were maintained in a rotating bioreactor with serum-free medium supplemented with transforming growth factor-beta1 for 4-12 weeks. Similar constructs seeded with fetal chondrocytes (n=13) were cultured in parallel for 8 weeks. All specimens were analyzed and compared with native fetal cartilage samples (n=10). Statistical analysis was by analysis of variance and Student's t-test (p<.01). At 12 weeks, CB constructs exhibited chondrogenic differentiation by both standard and matrix-specific staining. In the CB constructs, there was a significant time-dependent increase in extracellular matrix levels of glycosaminoglycans (GAGs) and type-II collagen (C-II) but not of elastin (EL). Fetal chondrocyte and CB constructs had similar GAG and C-II contents, but CB constructs had less EL. Compared with both hyaline and elastic native fetal cartilage, C-II and EL levels were, respectively, similar and lower in the CB constructs, which had correspondingly lower and similar GAG levels than native hyaline and elastic fetal cartilage. We conclude that CB mesenchymal progenitor cells can be successfully used for the engineering of 3D cartilaginous tissue in vitro, displaying select histological and functional properties of both native and engineered fetal cartilage. Cartilage engineered from CB may prove useful for the treatment of select congenital anomalies.

  8. Role of circulating osteogenic progenitor cells in calcific aortic stenosis.

    PubMed

    Gössl, Mario; Khosla, Sundeep; Zhang, Xin; Higano, Nara; Jordan, Kyra L; Loeffler, Darrell; Enriquez-Sarano, Maurice; Lennon, Ryan J; McGregor, Ulrike; Lerman, Lilach O; Lerman, Amir

    2012-11-06

    The purpose of this study was to determine the role of circulating endothelial progenitor cells with osteoblastic phenotype (EPC-OCN) in human aortic valve calcification (AVC). Recent evidence suggests that rather than passive mineralization, AVC is an active atherosclerotic process with an osteoblastic component resembling coronary calcification. We have recently identified circulating EPCs with osteogenic properties carrying both endothelial progenitor (CD34, KDR) and osteoblastic (osteocalcin [OCN]) cell surface markers. Blood samples from controls (n = 22) and patients with mild to moderate calcific aortic stenosis (mi-moAS, n = 17), severe calcific AS (sAS, n = 26), and both sAS and severe coronary artery disease (sCAD) (n = 33) were collected during diagnostic coronary angiography. By using flow cytometry, peripheral blood mononuclear cells were analyzed for CD34, KDR, and OCN. Resected normal and calcified aortic valves were analyzed histologically. Patients with mi-moAS and patients with sAS/sCAD had significantly less EPCs (CD34+/KDR+/OCN-) than controls. Patients with sAS showed significantly higher numbers of EPC-OCN (CD34+/KDR+/OCN+) than controls. In addition, the percentage of EPC costaining for OCN was higher in all disease groups compared with controls. A subgroup analysis of younger patients with bicuspid sAS showed a similar pattern of significantly lower EPCs but a high percentage of coexpression of OCN. Immunofluorescence showed colocalization of nuclear factor kappa-B and OCN in diseased and normal valves. CD34+/OCN+ cells were abundant in the endothelial and deeper cell layers of calcific aortic valve tissue but not in normal aortic valve tissue. Circulating EPC-OCN may play a significant role in the pathogenesis and as markers of prognostication of calcific AS. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Human neural progenitor cells promote photoreceptor survival in retinal explants.

    PubMed

    Englund-Johansson, Ulrica; Mohlin, Camilla; Liljekvist-Soltic, Ingela; Ekström, Per; Johansson, Kjell

    2010-02-01

    Different types of progenitor and stem cells have been shown to provide neuroprotection in animal models of photoreceptor degeneration. The present study was conducted to investigate whether human neural progenitor cells (HNPCs) have neuroprotective properties on retinal explants models with calpain- and caspase-3-dependent photoreceptor cell death. In the first experiments, HNPCs in a feeder layer were co-cultured for 6 days either with postnatal rd1 mouse or normal rat retinas. Retinal histological sections were used to determine outer nuclear layer (ONL) thickness, and to detect the number of photoreceptors with labeling for calpain activity, cleaved caspase-3 and TUNEL. The ONL thickness of co-cultured rat and rd1 retinas was found to be almost 10% and 40% thicker, respectively, compared to controls. Cell counts of calpain activity, cleaved caspase-3 and TUNEL labeled photoreceptors in both models revealed a 30-50% decrease when co-cultured with HNPCs. The results represent significant increases of photoreceptor survival in the co-cultured retinas. In the second experiments, for an identification of putative survival factors, or a combination of them, a growth factor profile was performed on conditioned medium. The relative levels of various growth factors were analyzed by densitometric measurements of growth factor array membranes. Following growth factors were identified as most potential survival factors; granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GMCSF), insulin-like growth factor II (IGF-II), neurotrophic factor 3 (NT-3), placental growth factor (PIGF), transforming growth factors (TGF-beta1 and TGF-beta2) and vascular endothelial growth factor (VEGF-D). HNPCs protect both against calpain- and caspase-3-dependent photoreceptor cell death in the rd1 mouse and against caspase-3-dependent photoreceptor cell death in normal rat retinas in vitro. The protective effect is possibly achieved by a variety of

  10. Isolated rat cortical progenitor cells are maintained in division in vitro by membrane-associated factors.

    PubMed

    Temple, S; Davis, A A

    1994-04-01

    Ventricular zone cells in the developing CNS undergo extensive cell division in vivo and under certain conditions in vitro. The culture conditions that promote cell division have been studied to determine the role that contact with cell membrane associated factors play in the proliferation of these cells. Progenitor cells have been taken from the ventricular zone of developing rat cerebral cortex and placed into microwells. Small clusters of these cells can generate large numbers of neurons and non-neuronal progeny. In contrast, single progenitor cells largely cease division, approximately 90% acquiring neuron-like characteristics by 1 day in vitro. DiI-labeled, single cells from embryonic day 14 cortex plated onto clusters of unmarked progenitor cells have a significantly higher probability (approximately 3-fold) of maintaining a progenitor cell phenotype than if plated onto the plastic substratum around 100 microns away from the clusters. Contact with purified astrocytes also promotes the progenitor cell phenotype, whereas contact with meningeal fibroblasts or balb3T3 cells promotes their differentiation. Membrane homogenates from cortical astrocytes stimulate significantly more incorporation of BrdU by E14 cortical progenitor cells than membrane homogenates from meningeal fibroblasts. These data indicate that the proliferation of rat cortical progenitor cells can be maintained by cell-type specific, membrane-associated factors.

  11. Slit/Robo signaling modulates the proliferation of central nervous system progenitors.

    PubMed

    Borrell, Víctor; Cárdenas, Adrián; Ciceri, Gabriele; Galcerán, Joan; Flames, Nuria; Pla, Ramón; Nóbrega-Pereira, Sandrina; García-Frigola, Cristina; Peregrín, Sandra; Zhao, Zhen; Ma, Le; Tessier-Lavigne, Marc; Marín, Oscar

    2012-10-18

    Neurogenesis relies on a delicate balance between progenitor maintenance and neuronal production. Progenitors divide symmetrically to increase the pool of dividing cells. Subsequently, they divide asymmetrically to self-renew and produce new neurons or, in some brain regions, intermediate progenitor cells (IPCs). Here we report that central nervous system progenitors express Robo1 and Robo2, receptors for Slit proteins that regulate axon guidance, and that absence of these receptors or their ligands leads to loss of ventricular mitoses. Conversely, production of IPCs is enhanced in Robo1/2 and Slit1/2 mutants, suggesting that Slit/Robo signaling modulates the transition between primary and intermediate progenitors. Unexpectedly, these defects do not lead to transient overproduction of neurons, probably because supernumerary IPCs fail to detach from the ventricular lining and cycle very slowly. At the molecular level, the role of Slit/Robo in progenitor cells involves transcriptional activation of the Notch effector Hes1. These findings demonstrate that Robo signaling modulates progenitor cell dynamics in the developing brain.

  12. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development.

    PubMed

    Bello, Bruno C; Izergina, Natalya; Caussinus, Emmanuel; Reichert, Heinrich

    2008-02-19

    In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  13. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver

    PubMed Central

    Benhamouche, Samira; Curto, Marcello; Saotome, Ichiko; Gladden, Andrew B.; Liu, Ching-Hui; Giovannini, Marco; McClatchey, Andrea I.

    2010-01-01

    The molecular signals that control the maintenance and activation of liver stem/progenitor cells are poorly understood, and the role of liver progenitor cells in hepatic tumorigenesis is unclear. We report here that liver-specific deletion of the neurofibromatosis type 2 (Nf2) tumor suppressor gene in the developing or adult mouse specifically yields a dramatic, progressive expansion of progenitor cells throughout the liver without affecting differentiated hepatocytes. All surviving mice eventually developed both cholangiocellular and hepatocellular carcinoma, suggesting that Nf2−/− progenitors can be a cell of origin for these tumors. Despite the suggested link between Nf2 and the Hpo/Wts/Yki signaling pathway in Drosophila, and recent studies linking the corresponding Mst/Lats/Yap pathway to mammalian liver tumorigenesis, our molecular studies suggest that Merlin is not a major regulator of YAP in liver progenitors, and that the overproliferation of Nf2−/− liver progenitors is instead driven by aberrant epidermal growth factor receptor (EGFR) activity. Indeed, pharmacologic inhibition of EGFR blocks the proliferation of Nf2−/− liver progenitors in vitro and in vivo, consistent with recent studies indicating that the Nf2-encoded protein Merlin can control the abundance and signaling of membrane receptors such as EGFR. Together, our findings uncover a critical role for Nf2/Merlin in controlling homeostasis of the liver stem cell niche. PMID:20675406

  14. Matrix adhesion polarizes heart progenitor induction in the invertebrate chordate Ciona intestinalis

    PubMed Central

    Norton, Jennifer; Cooley, James; Islam, A. F. M. Tariqul; Cota, Christina D.; Davidson, Brad

    2013-01-01

    Cell-matrix adhesion strongly influences developmental signaling. Resulting impacts on cell migration and tissue morphogenesis are well characterized. However, the in vivo impact of adhesion on fate induction remains ambiguous. Here, we employ the invertebrate chordate Ciona intestinalis to delineate an essential in vivo role for matrix adhesion in heart progenitor induction. In Ciona pre-cardiac founder cells, invasion of the underlying epidermis promotes localized induction of the heart progenitor lineage. We found that these epidermal invasions are associated with matrix adhesion along the pre-cardiac cell/epidermal boundary. Through targeted manipulations of RAP GTPase activity, we were able to manipulate pre-cardiac cell-matrix adhesion. Targeted disruption of pre-cardiac cell-matrix adhesion blocked heart progenitor induction. Conversely, increased matrix adhesion generated expanded induction. We were also able to selectively restore cell-matrix adhesion and heart progenitor induction through targeted expression of Ci-Integrin β2. These results indicate that matrix adhesion functions as a necessary and sufficient extrinsic cue for regional heart progenitor induction. Furthermore, time-lapse imaging suggests that cytokinesis acts as an intrinsic temporal regulator of heart progenitor adhesion and induction. Our findings highlight a potentially conserved role for matrix adhesion in early steps of vertebrate heart progenitor specification. PMID:23444358

  15. Thymus-autonomous T cell development in the absence of progenitor import

    PubMed Central

    Martins, Vera C.; Ruggiero, Eliana; Schlenner, Susan M.; Madan, Vikas; Schmidt, Manfred; Fink, Pamela J.; von Kalle, Christof

    2012-01-01

    Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self-renewal capacity is based on thymus transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell–deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2−/−γc−/−KitW/Wv mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2−/−γc−/−KitW/Wv hosts, γc-mediated signals alone played a key role in the competition between thymus-resident and bone marrow–derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus. PMID:22778389

  16. Matrix adhesion polarizes heart progenitor induction in the invertebrate chordate Ciona intestinalis.

    PubMed

    Norton, Jennifer; Cooley, James; Islam, A F M Tariqul; Cota, Christina D; Davidson, Brad

    2013-03-01

    Cell-matrix adhesion strongly influences developmental signaling. Resulting impacts on cell migration and tissue morphogenesis are well characterized. However, the in vivo impact of adhesion on fate induction remains ambiguous. Here, we employ the invertebrate chordate Ciona intestinalis to delineate an essential in vivo role for matrix adhesion in heart progenitor induction. In Ciona pre-cardiac founder cells, invasion of the underlying epidermis promotes localized induction of the heart progenitor lineage. We found that these epidermal invasions are associated with matrix adhesion along the pre-cardiac cell/epidermal boundary. Through targeted manipulations of RAP GTPase activity, we were able to manipulate pre-cardiac cell-matrix adhesion. Targeted disruption of pre-cardiac cell-matrix adhesion blocked heart progenitor induction. Conversely, increased matrix adhesion generated expanded induction. We were also able to selectively restore cell-matrix adhesion and heart progenitor induction through targeted expression of Ci-Integrin β2. These results indicate that matrix adhesion functions as a necessary and sufficient extrinsic cue for regional heart progenitor induction. Furthermore, time-lapse imaging suggests that cytokinesis acts as an intrinsic temporal regulator of heart progenitor adhesion and induction. Our findings highlight a potentially conserved role for matrix adhesion in early steps of vertebrate heart progenitor specification.

  17. Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line.

    PubMed

    Steiner, Aaron B; Kim, Taeryn; Cabot, Victoria; Hudspeth, A J

    2014-04-08

    Hearing loss is most commonly caused by the destruction of mechanosensory hair cells in the ear. This condition is usually permanent: Despite the presence of putative hair-cell progenitors in the cochlea, hair cells are not naturally replenished in adult mammals. Unlike those of the mammalian ear, the progenitor cells of nonmammalian vertebrates can regenerate hair cells throughout life. The basis of this difference remains largely unexplored but may lie in molecular dissimilarities that affect how progenitors respond to hair-cell death. To approach this issue, we analyzed gene expression in hair-cell progenitors of the lateral-line system. We developed a transgenic line of zebrafish that expresses a red fluorescent protein in the presumptive hair-cell progenitors known as mantle cells. Fluorescence-activated cell sorting from the skins of transgenic larvae, followed by microarray-based expression analysis, revealed a constellation of transcripts that are specifically enriched in these cells. Gene expression analysis after hair-cell ablation uncovered a cohort of genes that are differentially regulated early in regeneration, suggesting possible roles in the response of progenitors to hair-cell death. These results provide a resource for studying hair-cell regeneration and the biology of sensory progenitor cells.

  18. Distal airway epithelial progenitor cells are radiosensitive to High-LET radiation

    PubMed Central

    McConnell, Alicia M.; Konda, Bindu; Kirsch, David G.; Stripp, Barry R.

    2016-01-01

    Exposure to high-linear energy transfer (LET) radiation occurs in a variety of situations, including charged particle radiotherapy, radiological accidents, and space travel. However, the extent of normal tissue injury in the lungs following high-LET radiation exposure is unknown. Here we show that exposure to high-LET radiation led to a prolonged loss of in vitro colony forming ability by airway epithelial progenitor cells. Furthermore, exposure to high-LET radiation induced clonal expansion of a subset of progenitor cells in the distal airway epithelium. Clonal expansion following high-LET radiation exposure was correlated with elevated progenitor cell apoptosis, persistent γ-H2AX foci, and defects in mitotic progression of distal airway progenitors. We discovered that the effects of high-LET radiation exposure on progenitor cells occur in a p53-dependent manner. These data show that high-LET radiation depletes the distal airway progenitor pool by inducing cell death and loss of progenitor function, leading to clonal expansion. Importantly, high-LET radiation induces greater long-term damage to normal lung tissue than the relative equivalent dose of low-LET γ-rays, which has implications in therapeutic development and risk assessment. PMID:27659946

  19. Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line

    PubMed Central

    Kim, Taeryn; Cabot, Victoria; Hudspeth, A. J.

    2014-01-01

    Hearing loss is most commonly caused by the destruction of mechanosensory hair cells in the ear. This condition is usually permanent: Despite the presence of putative hair-cell progenitors in the cochlea, hair cells are not naturally replenished in adult mammals. Unlike those of the mammalian ear, the progenitor cells of nonmammalian vertebrates can regenerate hair cells throughout life. The basis of this difference remains largely unexplored but may lie in molecular dissimilarities that affect how progenitors respond to hair-cell death. To approach this issue, we analyzed gene expression in hair-cell progenitors of the lateral-line system. We developed a transgenic line of zebrafish that expresses a red fluorescent protein in the presumptive hair-cell progenitors known as mantle cells. Fluorescence-activated cell sorting from the skins of transgenic larvae, followed by microarray-based expression analysis, revealed a constellation of transcripts that are specifically enriched in these cells. Gene expression analysis after hair-cell ablation uncovered a cohort of genes that are differentially regulated early in regeneration, suggesting possible roles in the response of progenitors to hair-cell death. These results provide a resource for studying hair-cell regeneration and the biology of sensory progenitor cells. PMID:24706895

  20. Laminin promotes metalloproteinase-mediated dystroglycan processing to regulate oligodendrocyte progenitor cell proliferation.

    PubMed

    Leiton, Cindy V; Aranmolate, Azeez; Eyermann, Christopher; Menezes, Michael J; Escobar-Hoyos, Luisa F; Husain, Solomon; Winder, Steve J; Colognato, Holly

    2015-11-01

    The cell surface receptor dystroglycan mediates interactions between oligodendroglia and laminin-211, an extracellular matrix protein that regulates timely oligodendroglial development. However, dystroglycan's precise role in oligodendroglial development and the potential mechanisms to regulate laminin-dystroglycan interactions remain unknown. Here we report that oligodendroglial dystroglycan is cleaved by metalloproteinases, thereby uncoupling oligodendroglia from laminin binding. Dystroglycan cleavage is selectively stimulated by oligodendrocyte progenitor cell attachment to laminin-211, but not laminin-111 or poly-D-lysine. In addition, dystroglycan cleavage occurs most prominently in oligodendrocyte progenitor cells, with limited dystroglycan cleavage observed in differentiating oligodendrocytes. When dystroglycan cleavage is blocked by metalloproteinase inhibitors, oligodendrocyte progenitor cell proliferation is substantially decreased. Conversely, expression of the intracellular portion of cleaved dystroglycan results in increased oligodendrocyte progenitor cell proliferation, suggesting that endogenous dystroglycan cleavage may promote oligodendrocyte progenitor cell cycle progression. Intriguingly, while matrix metalloproteinase-2 and/or -9 have been reported to be responsible for dystroglycan cleavage, we find that these two metalloproteinases are neither necessary nor sufficient for cleavage of oligodendroglial dystroglycan. In summary, laminin-211 stimulates metalloproteinase-mediated dystroglycan cleavage in oligodendrocyte progenitor cells (but not in differentiated oligodendrocytes), which in turn promotes oligodendrocyte progenitor cell proliferation. This novel regulation of oligodendroglial laminin-dystroglycan interactions may have important consequences for oligodendroglial differentiation, both during development and during disease when metalloproteinase levels become elevated. © 2015 International Society for Neurochemistry.

  1. Thymus-autonomous T cell development in the absence of progenitor import.

    PubMed

    Martins, Vera C; Ruggiero, Eliana; Schlenner, Susan M; Madan, Vikas; Schmidt, Manfred; Fink, Pamela J; von Kalle, Christof; Rodewald, Hans-Reimer

    2012-07-30

    Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self-renewal capacity is based on thymus transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell-deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2(-/-)γ(c)(-/-)Kit(W/Wv) mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2(-/-)γ(c)(-/-)Kit(W/Wv) hosts, γ(c)-mediated signals alone played a key role in the competition between thymus-resident and bone marrow-derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus.

  2. 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

  3. Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex.

    PubMed

    Stenzel, Denise; Wilsch-Bräuninger, Michaela; Wong, Fong Kuan; Heuer, Heike; Huttner, Wieland B

    2014-02-01

    Neocortex expansion during evolution is associated with the enlargement of the embryonic subventricular zone, which reflects an increased self-renewal and proliferation of basal progenitors. In contrast to human, the vast majority of mouse basal progenitors lack self-renewal capacity, possibly due to lack of a basal process contacting the basal lamina and downregulation of cell-autonomous production of extracellular matrix (ECM) constituents. Here we show that targeted activation of the ECM receptor integrin αvβ3 on basal progenitors in embryonic mouse neocortex promotes their expansion. Specifically, integrin αvβ3 activation causes an increased cell cycle re-entry of Pax6-negative, Tbr2-positive intermediate progenitors, rather than basal radial glia, and a decrease in the proportion of intermediate progenitors committed to neurogenic division. Interestingly, integrin αvβ3 is the only known cell surface receptor for thyroid hormones. Remarkably, tetrac, a thyroid hormone analog that inhibits the binding of thyroid hormones to integrin αvβ3, completely abolishes the intermediate progenitor expansion observed upon targeted integrin αvβ3 activation, indicating that this expansion requires the binding of thyroid hormones to integrin αvβ3. Convergence of ECM and thyroid hormones on integrin αvβ3 thus appears to be crucial for cortical progenitor proliferation and self-renewal, and hence for normal brain development and the evolutionary expansion of the neocortex.

  4. 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

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

    PubMed

    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.

  6. Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors.

    PubMed

    Kobayashi, Michihiro; Nabinger, Sarah C; Bai, Yunpeng; Yoshimoto, Momoko; Gao, Rui; Chen, Sisi; Yao, Chonghua; Dong, Yuanshu; Zhang, Lujuan; Rodriguez, Sonia; Yashiro-Ohtani, Yumi; Pear, Warren S; Carlesso, Nadia; Yoder, Mervin C; Kapur, Reuben; Kaplan, Mark H; Daniel Lacorazza, Hugo; Zhang, Zhong-Yin; Liu, Yan

    2017-04-01

    The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances stem cell factor/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors. Stem Cells 2017;35:1053-1064.

  7. Time-lapse live imaging of clonally related neural progenitor cells in the developing zebrafish forebrain.

    PubMed

    Dong, Zhiqiang; Wagle, Mahendra; Guo, Su

    2011-04-06

    Precise patterns of division, migration and differentiation of neural progenitor cells are crucial for proper brain development and function. To understand the behavior of neural progenitor cells in the complex in vivo environment, time-lapse live imaging of neural progenitor cells in an intact brain is critically required. In this video, we exploit the unique features of zebrafish embryos to visualize the development of forebrain neural progenitor cells in vivo. We use electroporation to genetically and sparsely label individual neural progenitor cells. Briefly, DNA constructs coding for fluorescent markers were injected into the forebrain ventricle of 22 hours post fertilization (hpf) zebrafish embryos and electric pulses were delivered immediately. Six hours later, the electroporated zebrafish embryos were mounted with low melting point agarose in glass bottom culture dishes. Fluorescently labeled neural progenitor cells were then imaged for 36 hours with fixed intervals under a confocal microscope using water dipping objective lens. The present method provides a way to gain insights into the in vivo development of forebrain neural progenitor cells and can be applied to other parts of the central nervous system of the zebrafish embryo.

  8. 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

  9. Long Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers.

    PubMed

    Irudayaswamy, Antony; Muthiah, Mark; Zhou, Lei; Hung, Hau; Jumat, Nur Halisah Bte; Haque, Jamil; Teoh, Narcissus; Farrell, Geoffrey; Riehle, Kimberly J; Lin, Jaymie Siqi; Su, Lin Lin; Chan, Jerry Ky; Choolani, Mahesh; Wong, P C; Wee, Aileen; Lim, Seng Gee; Campbell, Jean; Fausto, Nelson; Dan, Yock Young

    2017-09-28

    Liver progenitor cells have the potential to repair and regenerate a diseased liver. The success of any translational efforts, however, hinges on thorough understanding of the fate of these cells after transplant, especially in terms of long-term safety and efficacy. Here we report transplantation of a liver progenitor population isolated from human fetal livers into immune-permissive mice with follow-up up to 36 weeks after transplant. We found that human progenitor cells engraft and differentiate into functional human hepatocytes in the mouse, producing albumin, alpha-1-antitrypsin, and glycogen. They create tight junctions with mouse hepatocytes, with no evidence of cell fusion. Interestingly, they also differentiate into functional endothelial cell and bile duct cells. Transplantation of progenitor cells abrogated carbon tetrachloride-induced fibrosis in recipient mice, with down-regulation of procollagen and anti-smooth muscle actin. Paradoxically, the degree of engraftment of human hepatocytes correlated negatively with the anti-fibrotic effect. Progenitor cell expansion was most prominent in cirrhotic animals, and correlated with transcript levels of pro-fibrotic genes. Animals that had resolution of fibrosis had quiescent native progenitor cells in their livers. No evidence of neoplasia was observed, even up to 9 months after transplantation. Human fetal liver progenitor cells successfully attenuate liver fibrosis in mice. They are activated in the setting of liver injury, but become quiescent when injury resolves, mimicking the behavior of de novo progenitor cells. Our data suggest that liver progenitor cells transplanted into injured livers maintain a functional role in the repair and regeneration of the liver. This article is protected by copyright. All rights reserved. © 2017 AlphaMed Press.

  10. 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.

  11. Characterization of Interstitial Cajal Progenitors Cells and Their Changes in Hirschsprung’s Disease

    PubMed Central

    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