Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage.

PubMed

Van Keymeulen, Alexandra; Fioramonti, Marco; Centonze, Alessia; Bouvencourt, Gaëlle; Achouri, Younes; Blanpain, Cédric

2017-08-15

The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER) + and ER - cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER + lineage is maintained by multipotent SCs or by lineage-restricted SCs. To this end, we generated doxycycline-inducible ER-rtTA mice that allowed us to perform genetic lineage tracing of ER + LCs and study their fate and long-term maintenance. Our results show that ER + cells are maintained by lineage-restricted SCs that exclusively contribute to the expansion of the ER + lineage during puberty and their maintenance during adult life. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Generation of enteroendocrine cell diversity in midgut stem cell lineages

PubMed Central

Beehler-Evans, Ryan; Micchelli, Craig A.

2015-01-01

The endocrine system mediates long-range peptide hormone signaling to broadcast changes in metabolic status to distant target tissues via the circulatory system. In many animals, the diffuse endocrine system of the gut is the largest endocrine tissue, with the full spectrum of endocrine cell subtypes not yet fully characterized. Here, we combine molecular mapping, lineage tracing and genetic analysis in the adult fruit fly to gain new insight into the cellular and molecular mechanisms governing enteroendocrine cell diversity. Neuropeptide hormone distribution was used as a basis to generate a high-resolution cellular map of the diffuse endocrine system. Our studies show that cell diversity is seen at two distinct levels: regional and local. We find that class I and class II enteroendocrine cells can be distinguished locally by combinatorial expression of secreted neuropeptide hormones. Cell lineage tracing studies demonstrate that class I and class II cells arise from a common stem cell lineage and that peptide profiles are a stable feature of enteroendocrine cell identity during homeostasis and following challenge with the enteric pathogen Pseudomonas entomophila. Genetic analysis shows that Notch signaling controls the establishment of class II cells in the lineage, but is insufficient to reprogram extant class I cells into class II enteroendocrine cells. Thus, one mechanism by which secretory cell diversity is achieved in the diffuse endocrine system is through cell-cell signaling interactions within individual adult stem cell lineages. PMID:25670792

Epigenomic Analysis of Multi-lineage Differentiation of Human Embryonic Stem Cells

PubMed Central

Xie, Wei; Schultz, Matthew D.; Lister, Ryan; Hou, Zhonggang; Rajagopal, Nisha; Ray, Pradipta; Whitaker, John W.; Tian, Shulan; Hawkins, R. David; Leung, Danny; Yang, Hongbo; Wang, Tao; Lee, Ah Young; Swanson, Scott A.; Zhang, Jiuchun; Zhu, Yun; Kim, Audrey; Nery, Joseph R.; Urich, Mark A.; Kuan, Samantha; Yen, Chia-an; Klugman, Sarit; Yu, Pengzhi; Suknuntha, Kran; Propson, Nicholas E.; Chen, Huaming; Edsall, Lee E.; Wagner, Ulrich; Li, Yan; Ye, Zhen; Kulkarni, Ashwinikumar; Xuan, Zhenyu; Chung, Wen-Yu; Chi, Neil C.; Antosiewicz-Bourget, Jessica E.; Slukvin, Igor; Stewart, Ron; Zhang, Michael Q.; Wang, Wei; Thomson, James A.; Ecker, Joseph R.; Ren, Bing

2013-01-01

SUMMARY Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells, and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in non-expressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation. PMID:23664764

Cell Expansion During Directed Differentiation of Stem Cells Toward the Hepatic Lineage

PubMed Central

Raju, Ravali; Chau, David; Cho, Dong Seong; Park, Yonsil; Verfaillie, Catherine M.

2017-01-01

The differentiation of human pluripotent stem cells toward the hepatocyte lineage can potentially provide an unlimited source of functional hepatocytes for transplantation and extracorporeal bioartificial liver applications. It is anticipated that the quantities of cells needed for these applications will be in the order of 109–1010 cells, because of the size of the liver. An ideal differentiation protocol would be to enable directed differentiation to the hepatocyte lineage with simultaneous cell expansion. We introduced a cell expansion stage after the commitment of human embryonic stem cells to the endodermal lineage, to allow for at least an eightfold increase in cell number, with continuation of cell maturation toward the hepatocyte lineage. The progressive changes in the transcriptome were measured by expression array, and the expression dynamics of certain lineage markers was measured by mass cytometry during the differentiation and expansion process. The findings revealed that while cells were expanding they were also capable of progressing in their differentiation toward the hepatocyte lineage. In addition, our transcriptome, protein and functional studies, including albumin secretion, drug-induced CYP450 expression and urea production, all indicated that the hepatocyte-like cells obtained with or without cell expansion are very similar. This method of simultaneous cell expansion and hepatocyte differentiation should facilitate obtaining large quantities of cells for liver cell applications. PMID:27806669

Cell Expansion During Directed Differentiation of Stem Cells Toward the Hepatic Lineage.

PubMed

Raju, Ravali; Chau, David; Cho, Dong Seong; Park, Yonsil; Verfaillie, Catherine M; Hu, Wei-Shou

2017-02-15

The differentiation of human pluripotent stem cells toward the hepatocyte lineage can potentially provide an unlimited source of functional hepatocytes for transplantation and extracorporeal bioartificial liver applications. It is anticipated that the quantities of cells needed for these applications will be in the order of 10 9 -10 10 cells, because of the size of the liver. An ideal differentiation protocol would be to enable directed differentiation to the hepatocyte lineage with simultaneous cell expansion. We introduced a cell expansion stage after the commitment of human embryonic stem cells to the endodermal lineage, to allow for at least an eightfold increase in cell number, with continuation of cell maturation toward the hepatocyte lineage. The progressive changes in the transcriptome were measured by expression array, and the expression dynamics of certain lineage markers was measured by mass cytometry during the differentiation and expansion process. The findings revealed that while cells were expanding they were also capable of progressing in their differentiation toward the hepatocyte lineage. In addition, our transcriptome, protein and functional studies, including albumin secretion, drug-induced CYP450 expression and urea production, all indicated that the hepatocyte-like cells obtained with or without cell expansion are very similar. This method of simultaneous cell expansion and hepatocyte differentiation should facilitate obtaining large quantities of cells for liver cell applications.

Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution

PubMed Central

Spiewak, Jessica E.

2014-01-01

Summary Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage and mate choice and have played important roles in speciation. Here, we review recent studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns. PMID:25421288

Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in Drosophila melanogaster

PubMed Central

Matsuoka, Shinya; Armstrong, Alissa R.; Sampson, Leesa L.; Laws, Kaitlin M.; Drummond-Barbosa, Daniela

2017-01-01

Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-CoA production are upregulated, promoting a shift of glucose metabolism toward macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results show a functional relationship between specific metabolic pathways in adipocytes and distinct processes in the GSC lineage, suggesting the adipocyte metabolism–stem cell link as an important area of investigation in other stem cell systems. PMID:28396508

Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in Drosophila melanogaster.

PubMed

Matsuoka, Shinya; Armstrong, Alissa R; Sampson, Leesa L; Laws, Kaitlin M; Drummond-Barbosa, Daniela

2017-06-01

Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-CoA production are upregulated, promoting a shift of glucose metabolism toward macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results show a functional relationship between specific metabolic pathways in adipocytes and distinct processes in the GSC lineage, suggesting the adipocyte metabolism-stem cell link as an important area of investigation in other stem cell systems. Copyright © 2017 by the Genetics Society of America.

Different roles of TGF-β in the multi-lineage differentiation of stem cells

PubMed Central

Wang, Ming-Ke; Sun, Hui-Qin; Xiang, Ying-Chun; Jiang, Fan; Su, Yong-Ping; Zou, Zhong-Min

2012-01-01

Stem cells are a population of cells that has infinite or long-term self-renewal ability and can produce various kinds of descendent cells. Transforming growth factor β (TGF-β) family is a superfamily of growth factors, including TGF-β1, TGF-β2 and TGF-β3, bone morphogenetic proteins, activin/inhibin, and some other cytokines such as nodal, which plays very important roles in regulating a wide variety of biological processes, such as cell growth, differentiation, cell death. TGF-β, a pleiotropic cytokine, has been proved to be differentially involved in the regulation of multi-lineage differentiation of stem cells, through the Smad pathway, non-Smad pathways including mitogen-activated protein kinase pathways, phosphatidylinositol-3-kinase/AKT pathways and Rho-like GTPase signaling pathways, and their cross-talks. For instance, it is generally known that TGF-β promotes the differentiation of stem cells into smooth muscle cells, immature cardiomyocytes, chondrocytes, neurocytes, hepatic stellate cells, Th17 cells, and dendritic cells. However, TGF-β inhibits the differentiation of stem cells into myotubes, adipocytes, endothelial cells, and natural killer cells. Additionally, TGF-β can provide competence for early stages of osteoblastic differentiation, but at late stages TGF-β acts as an inhibitor. The three mammalian isoforms (TGF-β1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Understanding the mechanisms underlying the regulatory effect of TGF-β in the stem cell multi-lineage differentiation is of importance in stem cell biology, and will facilitate both basic research and clinical applications of stem cells. In this article, we discuss the current status and progress in our understanding of different mechanisms by which TGF-β controls multi-lineage differentiation of stem cells. PMID:22993659

Biomechanics of running indicates endothermy in bipedal dinosaurs.

PubMed

Pontzer, Herman; Allen, Vivian; Hutchinson, John R

2009-11-11

One of the great unresolved controversies in paleobiology is whether extinct dinosaurs were endothermic, ectothermic, or some combination thereof, and when endothermy first evolved in the lineage leading to birds. Although it is well established that high, sustained growth rates and, presumably, high activity levels are ancestral for dinosaurs and pterosaurs (clade Ornithodira), other independent lines of evidence for high metabolic rates, locomotor costs, or endothermy are needed. For example, some studies have suggested that, because large dinosaurs may have been homeothermic due to their size alone and could have had heat loss problems, ectothermy would be a more plausible metabolic strategy for such animals. Here we describe two new biomechanical approaches for reconstructing the metabolic rate of 14 extinct bipedal dinosauriforms during walking and running. These methods, well validated for extant animals, indicate that during walking and slow running the metabolic rate of at least the larger extinct dinosaurs exceeded the maximum aerobic capabilities of modern ectotherms, falling instead within the range of modern birds and mammals. Estimated metabolic rates for smaller dinosaurs are more ambiguous, but generally approach or exceed the ectotherm boundary. Our results support the hypothesis that endothermy was widespread in at least larger non-avian dinosaurs. It was plausibly ancestral for all dinosauriforms (perhaps Ornithodira), but this is perhaps more strongly indicated by high growth rates than by locomotor costs. The polarity of the evolution of endothermy indicates that rapid growth, insulation, erect postures, and perhaps aerobic power predated advanced "avian" lung structure and high locomotor costs.

Biomechanics of Running Indicates Endothermy in Bipedal Dinosaurs

PubMed Central

Pontzer, Herman; Allen, Vivian; Hutchinson, John R.

2009-01-01

Background One of the great unresolved controversies in paleobiology is whether extinct dinosaurs were endothermic, ectothermic, or some combination thereof, and when endothermy first evolved in the lineage leading to birds. Although it is well established that high, sustained growth rates and, presumably, high activity levels are ancestral for dinosaurs and pterosaurs (clade Ornithodira), other independent lines of evidence for high metabolic rates, locomotor costs, or endothermy are needed. For example, some studies have suggested that, because large dinosaurs may have been homeothermic due to their size alone and could have had heat loss problems, ectothermy would be a more plausible metabolic strategy for such animals. Methodology/Principal Findings Here we describe two new biomechanical approaches for reconstructing the metabolic rate of 14 extinct bipedal dinosauriforms during walking and running. These methods, well validated for extant animals, indicate that during walking and slow running the metabolic rate of at least the larger extinct dinosaurs exceeded the maximum aerobic capabilities of modern ectotherms, falling instead within the range of modern birds and mammals. Estimated metabolic rates for smaller dinosaurs are more ambiguous, but generally approach or exceed the ectotherm boundary. Conclusions/Significance Our results support the hypothesis that endothermy was widespread in at least larger non-avian dinosaurs. It was plausibly ancestral for all dinosauriforms (perhaps Ornithodira), but this is perhaps more strongly indicated by high growth rates than by locomotor costs. The polarity of the evolution of endothermy indicates that rapid growth, insulation, erect postures, and perhaps aerobic power predated advanced “avian” lung structure and high locomotor costs. PMID:19911059

Early cretaceous dinosaurs from the sahara.

PubMed

Sereno, P C; Wilson, J A; Larsson, H C; Dutheil, D B; Sues, H D

1994-10-14

A major question in Mesozoic biogeography is how the land-based dinosaurian radiation responded to fragmentation of Pangaea. A rich fossil record has been uncovered on northern continents that spans the Cretaceous, when continental isolation reached its peak. In contrast, dinosaur remains on southern continents are scarce. The discovery of dinosaurian skeletons from Lower Cretaceous beds in the southern Sahara shows that several lineages of tetanuran theropods and broad-toothed sauropods had a cosmopolitan distribution across Pangaea before the onset of continental fragmentation. The distinct dinosaurian faunas of Africa, South America, and Asiamerica arose during the Cretaceous by differential survival of once widespread lineages on land masses that were becoming increasingly isolated from one another.

The generation of the epicardial lineage from human pluripotent stem cells

PubMed Central

Witty, Alec D.; Mihic, Anton; Tam, Roger Y.; Fisher, Stephanie A.; Mikryukov, Alexander; Shoichet, Molly S.; Li, Ren-Ke; Kattman, Steven J.; Keller, Gordon

2014-01-01

The epicardium supports cardiomyocyte proliferation early in development and provides fibroblasts and vascular smooth muscle cells to the developing heart. The epicardium has been shown to play an important role during tissue remodeling after cardiac injury, making access to this cell lineage necessary for the study of regenerative medicine. Here we describe the generation of epicardial lineage cells from human pluripotent stem cells by stage-specific activation of the BMP and WNT signaling pathways. These cells display morphological characteristics and express markers of the epicardial lineage, including the transcription factors WT1 and TBX18 and the retinoic acid–producing enzyme ALDH1A2. When induced to undergo epicardial-tomesenchymal transition, the cells give rise to populations that display characteristics of the fibroblast and vascular smooth muscle lineages. These findings identify BMP and WNT as key regulators of the epicardial lineage in vitro and provide a model for investigating epicardial function in human development and disease. PMID:25240927

Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

PubMed

Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

2016-03-17

Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated.

Melanosome evolution indicates a key physiological shift within feathered dinosaurs.

PubMed

Li, Quanguo; Clarke, Julia A; Gao, Ke-Qin; Zhou, Chang-Fu; Meng, Qingjin; Li, Daliang; D'Alba, Liliana; Shawkey, Matthew D

2014-03-20

Inference of colour patterning in extinct dinosaurs has been based on the relationship between the morphology of melanin-containing organelles (melanosomes) and colour in extant bird feathers. When this relationship evolved relative to the origin of feathers and other novel integumentary structures, such as hair and filamentous body covering in extinct archosaurs, has not been evaluated. Here we sample melanosomes from the integument of 181 extant amniote taxa and 13 lizard, turtle, dinosaur and pterosaur fossils from the Upper-Jurassic and Lower-Cretaceous of China. We find that in the lineage leading to birds, the observed increase in the diversity of melanosome morphologies appears abruptly, near the origin of pinnate feathers in maniraptoran dinosaurs. Similarly, mammals show an increased diversity of melanosome form compared to all ectothermic amniotes. In these two clades, mammals and maniraptoran dinosaurs including birds, melanosome form and colour are linked and colour reconstruction may be possible. By contrast, melanosomes in lizard, turtle and crocodilian skin, as well as the archosaurian filamentous body coverings (dinosaur 'protofeathers' and pterosaur 'pycnofibres'), show a limited diversity of form that is uncorrelated with colour in extant taxa. These patterns may be explained by convergent changes in the key melanocortin system of mammals and birds, which is known to affect pleiotropically both melanin-based colouration and energetic processes such as metabolic rate in vertebrates, and may therefore support a significant physiological shift in maniraptoran dinosaurs.

Wear biomechanics in the slicing dentition of the giant horned dinosaur Triceratops

PubMed Central

Erickson, Gregory M.; Sidebottom, Mark A.; Kay, David I.; Turner, Kevin T.; Ip, Nathan; Norell, Mark A.; Sawyer, W. Gregory; Krick, Brandon A.

2015-01-01

Herbivorous reptiles rarely evolve occluding dentitions that allow for the mastication (chewing) of plant matter. Conversely, most herbivorous mammals have occluding teeth with complex tissue architectures that self-wear to complex morphologies for orally processing plants. Dinosaurs stand out among reptiles in that several lineages acquired the capacity to masticate. In particular, the horned ceratopsian dinosaurs, among the most successful Late Cretaceous dinosaurian lineages, evolved slicing dentitions for the exploitation of tough, bulky plant matter. We show how Triceratops, a 9-m-long ceratopsian, and its relatives evolved teeth that wore during feeding to create fullers (recessed central regions on cutting blades) on the chewing surfaces. This unique morphology served to reduce friction during feeding. It was achieved through the evolution of a complex suite of osseous dental tissues rivaling the complexity of mammalian dentitions. Tribological (wear) properties of the tissues are preserved in ~66-million-year-old teeth, allowing the creation of a sophisticated three-dimensional biomechanical wear model that reveals how the complexes synergistically wore to create these implements. These findings, along with similar discoveries in hadrosaurids (duck-billed dinosaurs), suggest that tissue-mediated changes in dental morphology may have played a major role in the remarkable ecological diversification of these clades and perhaps other dinosaurian clades capable of mastication. PMID:26601198

A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes

PubMed Central

Zhao, Xiangshan; Malhotra, Gautam K.; Band, Hamid; Band, Vimla

2011-01-01

Introduction: Emerging evidence suggests a direct role of cancer stem cells (CSCs) in the development of breast cancer. In vitro cellular models that recapitulate properties of CSCs are therefore highly desirable. We have previously shown that normal human mammary epithelial cells (hMECs) immortalized with human telomerase reverse transcriptase (hTERT) possess properties of mammary stem / progenitor cells. Materials and Methods: In the present study, we used this cell system to test the idea that other known hMEC-immortalizing oncogenes (RhoA, HPVE6, HPVE7, p53 mutant, and treatment with γ-radiation), share with hTERT, the ability to maintain mammary stem / progenitor cells. Results: The results presented here demonstrate that similar to hMECs immortalized with hTERT, all hMEC cell lines immortalized using various oncogenic strategies express stem / progenitor cell markers. Furthermore, analyses using 2D and 3D culture assays demonstrate that all the immortal cell lines retain their ability to self-renew and to differentiate along the luminal lineage. Remarkably, the stem / progenitor cell lines generated using various oncogenic strategies exhibit a block in differentiation along the myoepithelial lineage, a trait that is retained on hTERT-immortalized stem / progenitors. The inability to differentiate along the myoepithelial lineage could be induced by ectopic mutant p53 expression in hTERT-immortalized hMEC. Conclusions: Our studies demonstrate that stem / progenitor cell characteristics of hMECs are maintained upon immortalization by using various cancer-relevant oncogenic strategies. Oncogene-immortalized hMECs show a block in their ability to differentiate along the myoepithelial lineage. Abrogation of the myoepithelial differentiation potential by a number of distinct oncogenic insults suggests a potential explanation for the predominance of luminal and rarity of myoepithelial breast cancers. PMID:22279424

A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes.

PubMed

Zhao, Xiangshan; Malhotra, Gautam K; Band, Hamid; Band, Vimla

2011-01-01

Emerging evidence suggests a direct role of cancer stem cells (CSCs) in the development of breast cancer. In vitro cellular models that recapitulate properties of CSCs are therefore highly desirable. We have previously shown that normal human mammary epithelial cells (hMECs) immortalized with human telomerase reverse transcriptase (hTERT) possess properties of mammary stem / progenitor cells. In the present study, we used this cell system to test the idea that other known hMEC-immortalizing oncogenes (RhoA, HPVE6, HPVE7, p53 mutant, and treatment with γ-radiation), share with hTERT, the ability to maintain mammary stem / progenitor cells. The results presented here demonstrate that similar to hMECs immortalized with hTERT, all hMEC cell lines immortalized using various oncogenic strategies express stem / progenitor cell markers. Furthermore, analyses using 2D and 3D culture assays demonstrate that all the immortal cell lines retain their ability to self-renew and to differentiate along the luminal lineage. Remarkably, the stem / progenitor cell lines generated using various oncogenic strategies exhibit a block in differentiation along the myoepithelial lineage, a trait that is retained on hTERT-immortalized stem / progenitors. The inability to differentiate along the myoepithelial lineage could be induced by ectopic mutant p53 expression in hTERT-immortalized hMEC. Our studies demonstrate that stem / progenitor cell characteristics of hMECs are maintained upon immortalization by using various cancer-relevant oncogenic strategies. Oncogene-immortalized hMECs show a block in their ability to differentiate along the myoepithelial lineage. Abrogation of the myoepithelial differentiation potential by a number of distinct oncogenic insults suggests a potential explanation for the predominance of luminal and rarity of myoepithelial breast cancers.

Dinosaurs.

ERIC Educational Resources Information Center

Miller, Vicki; Happel, Sue

Facts, activities, and student worksheets about dinosaurs are presented. General information about dinosaurs (when they lived and what they were like) and fossils (how they are created and what information they can provide) is followed by a worksheet and answer sheet. A timeline of the dinosaur age and a classification chart which divides…

Dinosaur Day!

ERIC Educational Resources Information Center

Nakamura, Sandra; Baptiste, H. Prentice

2006-01-01

In this article, the authors describe how they capitalized on their first-grade students' love of dinosaurs by hosting a fun-filled Dinosaur Day in their classroom. On Dinosaur Day, students rotated through four dinosaur-related learning stations that integrated science content with art, language arts, math, and history in a fun and time-efficient…

Adult stem cell lineage tracing and deep tissue imaging

PubMed Central

Fink, Juergen; Andersson-Rolf, Amanda; Koo, Bon-Kyoung

2015-01-01

Lineage tracing is a widely used method for understanding cellular dynamics in multicellular organisms during processes such as development, adult tissue maintenance, injury repair and tumorigenesis. Advances in tracing or tracking methods, from light microscopy-based live cell tracking to fluorescent label-tracing with two-photon microscopy, together with emerging tissue clearing strategies and intravital imaging approaches have enabled scientists to decipher adult stem and progenitor cell properties in various tissues and in a wide variety of biological processes. Although technical advances have enabled time-controlled genetic labeling and simultaneous live imaging, a number of obstacles still need to be overcome. In this review, we aim to provide an in-depth description of the traditional use of lineage tracing as well as current strategies and upcoming new methods of labeling and imaging. [BMB Reports 2015; 48(12): 655-667] PMID:26634741

SHIP1-expressing mesenchymal stem cells regulate hematopoietic stem cell homeostasis and lineage commitment during aging.

PubMed

Iyer, Sonia; Brooks, Robert; Gumbleton, Matthew; Kerr, William G

2015-05-01

Hematopoietic stem cell (HSC) self-renewal and lineage choice are subject to intrinsic control. However, this intrinsic regulation is also impacted by external cues provided by niche cells. There are multiple cellular components that participate in HSC support with the mesenchymal stem cell (MSC) playing a pivotal role. We had previously identified a role for SH2 domain-containing inositol 5'-phosphatase-1 (SHIP1) in HSC niche function through analysis of mice with germline or induced SHIP1 deficiency. In this study, we show that the HSC compartment expands significantly when aged in a niche that contains SHIP1-deficient MSC; however, this expanded HSC compartment exhibits a strong bias toward myeloid differentiation. In addition, we show that SHIP1 prevents chronic G-CSF production by the aging MSC compartment. These findings demonstrate that intracellular signaling by SHIP1 in MSC is critical for the control of HSC output and lineage commitment during aging. These studies increase our understanding of how myeloid bias occurs in aging and thus could have implications for the development of myeloproliferative disease in aging.

Sox2+ Stem Cells Contribute to All Epithelial Lineages of the Tooth via Sfrp5+ Progenitors

PubMed Central

Juuri, Emma; Saito, Kan; Ahtiainen, Laura; Seidel, Kerstin; Tummers, Mark; Hochedlinger, Konrad; Klein, Ophir D.; Thesleff, Irma; Michon, Frederic

2012-01-01

SUMMARY The continuously growing mouse incisor serves as a valuable model to study stem cell regulation during organ renewal. Epithelial stem cells are localized in the proximal end of the incisor in the labial cervical loop. Here, we show that the transcription factor Sox2 is a specific marker for these stem cells. Sox2+ cells became restricted to the labial cervical loop during tooth morphogenesis, and they contributed to the renewal of enamel-producing ameloblasts as well as all other epithelial cell lineages of the tooth. The early progeny of Sox2-positive stem cells transiently expressed the Wnt inhibitor Sfrp5. Sox2 expression was regulated by the tooth initiation marker FGF8 and specific miRNAs, suggesting a fine-tuning to maintain homeostasis of the dental epithelium. The identification of Sox2 as a marker for the dental epithelial stem cells will facilitate further studies on their lineage segregation and differentiation during tooth renewal. PMID:22819339

Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells.

PubMed

Semrau, Stefan; Goldmann, Johanna E; Soumillon, Magali; Mikkelsen, Tarjei S; Jaenisch, Rudolf; van Oudenaarden, Alexander

2017-10-23

Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues.

Signaling Molecules Governing Pluripotency and Early Lineage Commitments in Human Pluripotent Stem Cells

PubMed Central

Fathi, Ali; Eisa-Beygi, Shahram; Baharvand, Hossein

2017-01-01

Signaling in pluripotent stem cells is a complex and dynamic process involving multiple mediators, finely tuned to balancing pluripotency and differentiation states. Characterizing and modifying the necessary signaling pathways to attain desired cell types is required for stem-cell applications in various fields of regenerative medicine. These signals may help enhance the differentiation potential of pluripotent cells towards each of the embryonic lineages and enable us to achieve pure in vitro cultures of various cell types. This review provides a timely synthesis of recent advances into how maintenance of pluripotency in hPSCs is regulated by extrinsic cues, such as the fibroblast growth factor (FGF) and ACTIVIN signaling pathways, their interplay with other signaling pathways, namely, wingless- type MMTV integration site family (WNT) and mammalian target of rapamycin (mTOR), and the pathways governing the determination of multiple lineages. PMID:28670512

Developmental origin and lineage plasticity of endogenous cardiac stem cells

PubMed Central

Santini, Maria Paola; Forte, Elvira; Harvey, Richard P.; Kovacic, Jason C.

2016-01-01

Over the past two decades, several populations of cardiac stem cells have been described in the adult mammalian heart. For the most part, however, their lineage origins and in vivo functions remain largely unexplored. This Review summarizes what is known about different populations of embryonic and adult cardiac stem cells, including KIT+, PDGFRα+, ISL1+ and SCA1+ cells, side population cells, cardiospheres and epicardial cells. We discuss their developmental origins and defining characteristics, and consider their possible contribution to heart organogenesis and regeneration. We also summarize the origin and plasticity of cardiac fibroblasts and circulating endothelial progenitor cells, and consider what role these cells have in contributing to cardiac repair. PMID:27095490

Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

PubMed Central

Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine

2015-01-01

Adult stem cells (SCs) reside in niches which balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, SCs outside their niche often display fate flexibility1-4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult SCs in vivo. Using hair follicle (HF) as model, we map the global chromatin domains of HFSCs and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicenters’) of transcription factor (TF) binding sites change upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicenters, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, HFSCs dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicenters, enabling them to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of HFSC super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense TF-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status, but also stemness, plasticity in transitional states and differentiation. PMID:25799994

Dinosaur lactation?

PubMed

Else, Paul L

2013-02-01

Lactation is a process associated with mammals, yet a number of birds feed their newly hatched young on secretions analogous to the milk of mammals. These secretions are produced from various sections (crop organ, oesophageal lining and proventriculus) of the upper digestive tract and possess similar levels of fat and protein, as well as added carotenoids, antibodies and, in the case of pigeons and doves, epidermal growth factor. Parental care in avian species has been proposed to originate from dinosaurs. This study examines the possibility that some dinosaurs used secretory feeding to increase the rate of growth of their young, estimated to be similar to that of present day birds and mammals. Dinosaur 'lactation' could also have facilitated immune responses as well as extending parental protection as a result of feeding newly hatched young in nest environments. While the arguments for dinosaur lactation are somewhat generic, a case study for lactation in herbivorous site-nesting dinosaurs is presented. It is proposes that secretory feeding could have been used to bridge the gap between hatching and establishment of the normal diet in some dinosaurs.

Lineage specific expression of Polycomb Group Proteins in human embryonic stem cells in vitro.

PubMed

Pethe, Prasad; Pursani, Varsha; Bhartiya, Deepa

2015-05-01

Human embryonic (hES) stem cells are an excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression. PcG proteins form complexes called Polycomb Repressive Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1, H3K27me3, and H3K9me3. PcG proteins play a crucial role during differentiation of stem cells. The expression of PcG transcripts during differentiation of hES cells into endoderm, mesoderm, and ectoderm lineage is yet to be shown. In-house derived hES cell line KIND1 was differentiated into endoderm, mesoderm, and ectoderm lineages; followed by characterization using RT-PCR for HNF4A, CDX2, MEF2C, TBX5, SOX1, and MAP2. qRT-PCR and western blotting was performed to compare expression of PcG transcripts and proteins across all the three lineages. We observed that cells differentiated into endoderm showed upregulation of RING1B, BMI1, EZH2, and EED transcripts. Mesoderm differentiation was characterized by significant downregulation of all PcG transcripts during later stages. BMI1 and RING1B were upregulated while EZH2, SUZ12, and EED remained low during ectoderm differentiation. Western blotting also showed distinct expression of BMI1 and EZH2 during differentiation into three germ layers. Our study shows that hES cells differentiating into endoderm, mesoderm, and ectoderm lineages show distinct PcG expression profile at transcript and protein level. © 2015 International Federation for Cell Biology.

Generation of polyhormonal and multipotent pancreatic progenitor lineages from human pluripotent stem cells.

PubMed

Korytnikov, Roman; Nostro, Maria Cristina

2016-05-15

Generation of pancreatic β-cells from human pluripotent stem cells (hPSCs) has enormous importance in type 1 diabetes (T1D), as it is fundamental to a treatment strategy based on cellular therapeutics. Being able to generate β-cells, as well as other mature pancreatic cells, from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) will also enable the development of platforms that can be used for disease modeling and drug testing for a variety of pancreas-associated diseases, including cystic fibrosis. For this to occur, it is crucial to develop differentiation strategies that are robust and reproducible across cell lines and laboratories. In this article we describe two serum-free differentiation protocols designed to generate specific pancreatic lineages from hPSCs. Our approach employs a variety of cytokines and small molecules to mimic developmental pathways active during pancreatic organogenesis and allows for the in vitro generation of distinct pancreatic populations. The first protocol is designed to give rise to polyhormonal cells that have the potential to differentiate into glucagon-producing cells. The second protocol is geared to generate multipotent pancreatic progenitor cells, which harbor the potential to generate all pancreatic lineages including: monohormonal endocrine cells, acinar, and ductal cells. Copyright © 2016 Elsevier Inc. All rights reserved.

New Australian sauropods shed light on Cretaceous dinosaur palaeobiogeography

PubMed Central

Poropat, Stephen F.; Mannion, Philip D.; Upchurch, Paul; Hocknull, Scott A.; Kear, Benjamin P.; Kundrát, Martin; Tischler, Travis R.; Sloan, Trish; Sinapius, George H. K.; Elliott, Judy A.; Elliott, David A.

2016-01-01

Australian dinosaurs have played a rare but controversial role in the debate surrounding the effect of Gondwanan break-up on Cretaceous dinosaur distribution. Major spatiotemporal gaps in the Gondwanan Cretaceous fossil record, coupled with taxon incompleteness, have hindered research on this effect, especially in Australia. Here we report on two new sauropod specimens from the early Late Cretaceous of Queensland, Australia, that have important implications for Cretaceous dinosaur palaeobiogeography. Savannasaurus elliottorum gen. et sp. nov. comprises one of the most complete Cretaceous sauropod skeletons ever found in Australia, whereas a new specimen of Diamantinasaurus matildae includes the first ever cranial remains of an Australian sauropod. The results of a new phylogenetic analysis, in which both Savannasaurus and Diamantinasaurus are recovered within Titanosauria, were used as the basis for a quantitative palaeobiogeographical analysis of macronarian sauropods. Titanosaurs achieved a worldwide distribution by at least 125 million years ago, suggesting that mid-Cretaceous Australian sauropods represent remnants of clades which were widespread during the Early Cretaceous. These lineages would have entered Australasia via dispersal from South America, presumably across Antarctica. High latitude sauropod dispersal might have been facilitated by Albian–Turonian warming that lifted a palaeoclimatic dispersal barrier between Antarctica and South America. PMID:27763598

New Australian sauropods shed light on Cretaceous dinosaur palaeobiogeography.

PubMed

Poropat, Stephen F; Mannion, Philip D; Upchurch, Paul; Hocknull, Scott A; Kear, Benjamin P; Kundrát, Martin; Tischler, Travis R; Sloan, Trish; Sinapius, George H K; Elliott, Judy A; Elliott, David A

2016-10-20

Australian dinosaurs have played a rare but controversial role in the debate surrounding the effect of Gondwanan break-up on Cretaceous dinosaur distribution. Major spatiotemporal gaps in the Gondwanan Cretaceous fossil record, coupled with taxon incompleteness, have hindered research on this effect, especially in Australia. Here we report on two new sauropod specimens from the early Late Cretaceous of Queensland, Australia, that have important implications for Cretaceous dinosaur palaeobiogeography. Savannasaurus elliottorum gen. et sp. nov. comprises one of the most complete Cretaceous sauropod skeletons ever found in Australia, whereas a new specimen of Diamantinasaurus matildae includes the first ever cranial remains of an Australian sauropod. The results of a new phylogenetic analysis, in which both Savannasaurus and Diamantinasaurus are recovered within Titanosauria, were used as the basis for a quantitative palaeobiogeographical analysis of macronarian sauropods. Titanosaurs achieved a worldwide distribution by at least 125 million years ago, suggesting that mid-Cretaceous Australian sauropods represent remnants of clades which were widespread during the Early Cretaceous. These lineages would have entered Australasia via dispersal from South America, presumably across Antarctica. High latitude sauropod dispersal might have been facilitated by Albian-Turonian warming that lifted a palaeoclimatic dispersal barrier between Antarctica and South America.

Feeding height stratification among the herbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta, Canada

PubMed Central

2013-01-01

Background Herbivore coexistence on the Late Cretaceous island continent of Laramidia has been a topic of great interest, stemming from the paradoxically high diversity and biomass of these animals in relation to the relatively small landmass available to them. Various hypotheses have been advanced to account for these facts, of which niche partitioning is among the most frequently invoked. However, despite its wide acceptance, this hypothesis has not been rigorously tested. This study uses the fossil assemblage from the Dinosaur Park Formation of Alberta as a model to investigate whether niche partitioning facilitated herbivorous dinosaur coexistence on Laramidia. Specifically, the question of feeding height stratification is examined in light of the role it plays in facilitating modern ungulate coexistence. Results Most herbivorous dinosaur species from the Dinosaur Park Formation were restricted to feeding no higher than approximately 1 m above the ground. There is minimal evidence for feeding height partitioning at this level, with ceratopsids capable of feeding slightly higher than ankylosaurs, but the ecological significance of this is ambiguous. Hadrosaurids were uniquely capable of feeding up to 2 m quadrupedally, or up to 5 m bipedally. There is no evidence for either feeding height stratification within any of these clades, or for change in these ecological relationships through the approximately 1.5 Ma record of the Dinosaur Park Formation. Conclusions Although we cannot reject the possibility, we find no good evidence that feeding height stratification, as revealed by reconstructed maximum feeding heights, played an important role in facilitating niche partitioning among the herbivorous dinosaurs of Laramidia. Most browsing pressure was concentrated in the herb layer, although hadrosaurids were capable of reaching shrubs and low-growing trees that were out of reach from ceratopsids, ankylosaurs, and other small herbivores, effectively dividing the

Feeding height stratification among the herbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta, Canada.

PubMed

Mallon, Jordan C; Evans, David C; Ryan, Michael J; Anderson, Jason S

2013-04-04

Herbivore coexistence on the Late Cretaceous island continent of Laramidia has been a topic of great interest, stemming from the paradoxically high diversity and biomass of these animals in relation to the relatively small landmass available to them. Various hypotheses have been advanced to account for these facts, of which niche partitioning is among the most frequently invoked. However, despite its wide acceptance, this hypothesis has not been rigorously tested. This study uses the fossil assemblage from the Dinosaur Park Formation of Alberta as a model to investigate whether niche partitioning facilitated herbivorous dinosaur coexistence on Laramidia. Specifically, the question of feeding height stratification is examined in light of the role it plays in facilitating modern ungulate coexistence. Most herbivorous dinosaur species from the Dinosaur Park Formation were restricted to feeding no higher than approximately 1 m above the ground. There is minimal evidence for feeding height partitioning at this level, with ceratopsids capable of feeding slightly higher than ankylosaurs, but the ecological significance of this is ambiguous. Hadrosaurids were uniquely capable of feeding up to 2 m quadrupedally, or up to 5 m bipedally. There is no evidence for either feeding height stratification within any of these clades, or for change in these ecological relationships through the approximately 1.5 Ma record of the Dinosaur Park Formation. Although we cannot reject the possibility, we find no good evidence that feeding height stratification, as revealed by reconstructed maximum feeding heights, played an important role in facilitating niche partitioning among the herbivorous dinosaurs of Laramidia. Most browsing pressure was concentrated in the herb layer, although hadrosaurids were capable of reaching shrubs and low-growing trees that were out of reach from ceratopsids, ankylosaurs, and other small herbivores, effectively dividing the herbivores in terms of relative

Concise Review: Plasma and Nuclear Membranes Convey Mechanical Information to Regulate Mesenchymal Stem Cell Lineage.

PubMed

Uzer, Gunes; Fuchs, Robyn K; Rubin, Janet; Thompson, William R

2016-06-01

Numerous factors including chemical, hormonal, spatial, and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well-characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on "outside-in" signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell uses integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these outside-in connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the biochemical signals generated at the cell membrane and the nucleus, and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis. Stem Cells 2016;34:1455-1463. © 2016 AlphaMed Press.

Digging into Dinosaurs.

ERIC Educational Resources Information Center

Oleson, Barb

This four-week unit of study for grades 1-3 provides information and activities on 17 different dinosaurs. A 21-item pre- and post-test and a brief history of dinosaurs precede descriptions and full-page drawings of the following dinosaurs: (1) giant plant-eaters (brachiosaurus, brontosaurus, and diplodocus); (2) giant meat-eaters (allosaurus,…

Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells.

PubMed

Rostovskaya, Maria; Bredenkamp, Nicholas; Smith, Austin

2015-10-19

Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification. © 2015 The Authors.

Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa).

PubMed

Barfield, Sarah; Aglyamova, Galina V; Matz, Mikhail V

2016-01-13

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. © 2016 The Author(s).

Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa)

PubMed Central

Barfield, Sarah; Aglyamova, Galina V.; Matz, Mikhail V.

2016-01-01

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. PMID:26763699

Dinosaur Impressions

NASA Astrophysics Data System (ADS)

Taquet, Philippe

1998-09-01

Perhaps you are a paleontologist or have always wondered what it is like to be one. Or you are fascinated by fossils and like to read about the origins and natural history of dinosaurs. Or maybe you are an avid traveler and reader of travelogues. If you are any of these things, then this book is for you. Originally published in 1994 in French, Dinosaur Impressions is the engaging account of thirty years of travel and paleontological exploration by Philippe Taquet, one of the world's most noted paleontologists. Dr. Taquet takes the reader on a surprisingly far-flung tour ranging from the Provence countryside to the Niger desert, from the Brazilian bush to the Mongolian Steppes, and from the Laos jungle to the Moroccan mountains in search of dinosaur bones and what they have to tell us about a vanished world. With wry humor and lively anecdotes, Dr. Taquet retraces the history of paleontological research, along the way discussing the latest theories of dinosaur existence and extinction. Elegantly translated by Kevin Padian, Dinosaur Impressions provides a unique, thoughtful perspective not often encountered in American- and English-language works. This insightful, first-hand account of an exceptional career is also a travelogue par excellence that will enthrall enthusiasts and general readers alike. Philippe Taquet is the Director of the National Museum of Natural History in Paris and is a member of the French Academy of Sciences. Kevin Padian is a professor in the Department of Integrative Biology and Curator of the Museum of Paleontology at the University of California, Berkeley. He is also the editor of The Beginning of the Age of Dinosaurs (Cambridge, 1986) and The Encyclopedia of Dinosaurs (1997).

Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

PubMed Central

Soucie, Erinn L.; Weng, Ziming; Geirsdóttir, Laufey; Molawi, Kaaweh; Maurizio, Julien; Fenouil, Romain; Mossadegh-Keller, Noushine; Gimenez, Gregory; VanHille, Laurent; Beniazza, Meryam; Favret, Jeremy; Berruyer, Carole; Perrin, Pierre; Hacohen, Nir; Andrau, J.-C.; Ferrier, Pierre; Dubreuil, Patrice; Sidow, Arend; Sieweke, Michael H.

2016-01-01

Differentiated macrophages can self-renew in tissues and expand long-term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. Single cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells. PMID:26797145

The last polar dinosaurs: high diversity of latest Cretaceous arctic dinosaurs in Russia

NASA Astrophysics Data System (ADS)

Godefroit, Pascal; Golovneva, Lina; Shchepetov, Sergei; Garcia, Géraldine; Alekseev, Pavel

2009-04-01

A latest Cretaceous (68 to 65 million years ago) vertebrate microfossil assemblage discovered at Kakanaut in northeastern Russia reveals that dinosaurs were still highly diversified in Arctic regions just before the Cretaceous-Tertiary mass extinction event. Dinosaur eggshell fragments, belonging to hadrosaurids and non-avian theropods, indicate that at least several latest Cretaceous dinosaur taxa could reproduce in polar region and were probably year-round residents of high latitudes. Palaeobotanical data suggest that these polar dinosaurs lived in a temperate climate (mean annual temperature about 10°C), but the climate was apparently too cold for amphibians and ectothermic reptiles. The high diversity of Late Maastrichtian dinosaurs in high latitudes, where ectotherms are absent, strongly questions hypotheses according to which dinosaur extinction was a result of temperature decline, caused or not by the Chicxulub impact.

Dermal Stem Cells Can Differentiate Down an Endothelial Lineage

PubMed Central

Bell, Emma; Richardson, Gavin D.; Jahoda, Colin A.; Gledhill, Karl; Phillips, Helen M.; Henderson, Deborah; Owens, W. Andrew

2012-01-01

In this study, we have demonstrated that cells of neural crest origin located in the dermal papilla (DP) exhibit endothelial marker expression and a functional activity. When grown in endothelial growth media, DP primary cultures upregulate expression of vascular endothelial growth factor receptor 1 (FLT1) mRNA and downregulate expression of the dermal stem cell marker α-smooth muscle actin. DP cells have demonstrated functional characteristics of endothelial cells, including the ability to form capillary-like structures on Matrigel, increase uptake of low-density lipoprotein and upregulate ICAM1 (CD54) in response to tumour necrosis factor alpha (TNF-α) stimulation. We confirmed that these observations were not due to contaminating endothelial cells, by using DP clones. We have also used the WNT1cre/ROSA26R and WNT1cre/YFP lineage-tracing mouse models to identify a population of neural crest-derived cells in DP cultures that express the endothelial marker PECAM (CD31); these cells also form capillary-like structures on Matrigel. Importantly, cells of neural crest origin that express markers of endothelial and mesenchymal lineages exist within the dermal sheath of the vibrissae follicle. PMID:22571645

Dynamic Locomotor Capabilities Revealed by Early Dinosaur Trackmakers from Southern Africa

PubMed Central

Wilson, Jeffrey A.; Marsicano, Claudia A.; Smith, Roger M. H.

2009-01-01

Background A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. Methodology/Principal Findings The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31°), and plantigrade and digitigrade foot posture. Conclusions/Significance The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect ‘real time’ responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors. PMID:19806213

Dynamic locomotor capabilities revealed by early dinosaur trackmakers from southern Africa.

PubMed

Wilson, Jeffrey A; Marsicano, Claudia A; Smith, Roger M H

2009-10-06

A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31 degrees ), and plantigrade and digitigrade foot posture. The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect 'real time' responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.

A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages.

PubMed

Pearson, Bret J; Sánchez Alvarado, Alejandro

2010-01-01

The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus far. Planaria have a single p53 family member, Smed-p53, which is predominantly expressed in newly made stem cell progeny. When Smed-p53 is targeted by RNAi, the stem cell population increases at the expense of progeny, resulting in hyper-proliferation. However, ultimately the stem cell population fails to self-renew. Our results suggest that prior to the vertebrates, an ancestral p53-like molecule already had functions in stem cell proliferation control and self-renewal.

Dinosaur Extinction, Early Childhood Style

ERIC Educational Resources Information Center

Murray, Mary; Valentine-Anand, Lesley

2008-01-01

Do dinosaurs have bellybuttons? This intriguing question launched a journey into inquiry science that captivated a class of four-year-olds for eight months. As students enjoyed dinosaur books, examined dinosaur artifacts, drew pictures, watched videos, and generally immersed themselves in all things dinosaur, the authors built a culture of…

Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.

PubMed

Soucie, Erinn L; Weng, Ziming; Geirsdóttir, Laufey; Molawi, Kaaweh; Maurizio, Julien; Fenouil, Romain; Mossadegh-Keller, Noushine; Gimenez, Gregory; VanHille, Laurent; Beniazza, Meryam; Favret, Jeremy; Berruyer, Carole; Perrin, Pierre; Hacohen, Nir; Andrau, J-C; Ferrier, Pierre; Dubreuil, Patrice; Sidow, Arend; Sieweke, Michael H

2016-02-12

Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells. Copyright © 2016, American Association for the Advancement of Science.

New horned dinosaurs from Utah provide evidence for intracontinental dinosaur endemism.

PubMed

Sampson, Scott D; Loewen, Mark A; Farke, Andrew A; Roberts, Eric M; Forster, Catherine A; Smith, Joshua A; Titus, Alan L

2010-09-22

During much of the Late Cretaceous, a shallow, epeiric sea divided North America into eastern and western landmasses. The western landmass, known as Laramidia, although diminutive in size, witnessed a major evolutionary radiation of dinosaurs. Other than hadrosaurs (duck-billed dinosaurs), the most common dinosaurs were ceratopsids (large-bodied horned dinosaurs), currently known only from Laramidia and Asia. Remarkably, previous studies have postulated the occurrence of latitudinally arrayed dinosaur "provinces," or "biomes," on Laramidia. Yet this hypothesis has been challenged on multiple fronts and has remained poorly tested. Here we describe two new, co-occurring ceratopsids from the Upper Cretaceous Kaiparowits Formation of Utah that provide the strongest support to date for the dinosaur provincialism hypothesis. Both pertain to the clade of ceratopsids known as Chasmosaurinae, dramatically increasing representation of this group from the southern portion of the Western Interior Basin of North America. Utahceratops gettyi gen. et sp. nov.-characterized by short, rounded, laterally projecting supraorbital horncores and an elongate frill with a deep median embayment-is recovered as the sister taxon to Pentaceratops sternbergii from the late Campanian of New Mexico. Kosmoceratops richardsoni gen. et sp. nov.-characterized by elongate, laterally projecting supraorbital horncores and a short, broad frill adorned with ten well developed hooks-has the most ornate skull of any known dinosaur and is closely allied to Chasmosaurus irvinensis from the late Campanian of Alberta. Considered in unison, the phylogenetic, stratigraphic, and biogeographic evidence documents distinct, co-occurring chasmosaurine taxa north and south on the diminutive landmass of Laramidia. The famous Triceratops and all other, more nested chasmosaurines are postulated as descendants of forms previously restricted to the southern portion of Laramidia. Results further suggest the presence of

An evolutionary cascade model for sauropod dinosaur gigantism--overview, update and tests.

PubMed

Sander, P Martin

2013-01-01

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism"). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

A mex3 homolog is required for differentiation during planarian stem cell lineage development

PubMed Central

Zhu, Shu Jun; Hallows, Stephanie E; Currie, Ko W; Xu, ChangJiang; Pearson, Bret J

2015-01-01

Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment. DOI: http://dx.doi.org/10.7554/eLife.07025.001 PMID:26114597

Clonal analysis of lineage fate in native haematopoiesis.

PubMed

Rodriguez-Fraticelli, Alejo E; Wolock, Samuel L; Weinreb, Caleb S; Panero, Riccardo; Patel, Sachin H; Jankovic, Maja; Sun, Jianlong; Calogero, Raffaele A; Klein, Allon M; Camargo, Fernando D

2018-01-11

Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate. Here we use transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed haematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other haematopoietic fates. Our data, combined with single-cell RNA sequencing, identify a functional hierarchy of unilineage- and oligolineage-producing clones within the multipotent progenitor population. Finally, our results demonstrate that traditionally defined long-term haematopoietic stem cells are a significant source of megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage is the predominant native fate of long-term haematopoietic stem cells. Our study provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.

Dinosaur physiology. Evidence for mesothermy in dinosaurs.

PubMed

Grady, John M; Enquist, Brian J; Dettweiler-Robinson, Eva; Wright, Natalie A; Smith, Felisa A

2014-06-13

Were dinosaurs ectotherms or fast-metabolizing endotherms whose activities were unconstrained by temperature? To date, some of the strongest evidence for endothermy comes from the rapid growth rates derived from the analysis of fossil bones. However, these studies are constrained by a lack of comparative data and an appropriate energetic framework. Here we compile data on ontogenetic growth for extant and fossil vertebrates, including all major dinosaur clades. Using a metabolic scaling approach, we find that growth and metabolic rates follow theoretical predictions across clades, although some groups deviate. Moreover, when the effects of size and temperature are considered, dinosaur metabolic rates were intermediate to those of endotherms and ectotherms and closest to those of extant mesotherms. Our results suggest that the modern dichotomy of endothermic versus ectothermic is overly simplistic. Copyright © 2014, American Association for the Advancement of Science.

What's New, Dinosaur?

ERIC Educational Resources Information Center

Prime, Carol Spirkoff; Cox, Judy

1987-01-01

Activities and information relating to dinosaurs are presented, including: study of warm- and cold-blooded animals; research about recent dinosaur discoveries; track-making; studying and making fossils; and extinction theories. (CB)

Bony cranial ornamentation linked to rapid evolution of gigantic theropod dinosaurs

NASA Astrophysics Data System (ADS)

Gates, Terry A.; Organ, Chris; Zanno, Lindsay E.

2016-09-01

Exaggerated cranial structures such as crests and horns, hereafter referred to collectively as ornaments, are pervasive across animal species. These structures perform vital roles in visual communication and physical interactions within and between species. Yet the origin and influence of ornamentation on speciation and ecology across macroevolutionary time scales remains poorly understood for virtually all animals. Here, we explore correlative evolution of osseous cranial ornaments with large body size in theropod dinosaurs using a phylogenetic comparative framework. We find that body size evolved directionally toward phyletic giantism an order of magnitude faster in theropod species possessing ornaments compared with unadorned lineages. In addition, we find a body mass threshold below which bony cranial ornaments do not originate. Maniraptoriform dinosaurs generally lack osseous cranial ornaments despite repeatedly crossing this body size threshold. Our study provides novel, quantitative support for a shift in selective pressures on socio-sexual display mechanisms in theropods coincident with the evolution of pennaceous feathers.

Bony cranial ornamentation linked to rapid evolution of gigantic theropod dinosaurs

PubMed Central

Gates, Terry A.; Organ, Chris; Zanno, Lindsay E.

2016-01-01

Exaggerated cranial structures such as crests and horns, hereafter referred to collectively as ornaments, are pervasive across animal species. These structures perform vital roles in visual communication and physical interactions within and between species. Yet the origin and influence of ornamentation on speciation and ecology across macroevolutionary time scales remains poorly understood for virtually all animals. Here, we explore correlative evolution of osseous cranial ornaments with large body size in theropod dinosaurs using a phylogenetic comparative framework. We find that body size evolved directionally toward phyletic giantism an order of magnitude faster in theropod species possessing ornaments compared with unadorned lineages. In addition, we find a body mass threshold below which bony cranial ornaments do not originate. Maniraptoriform dinosaurs generally lack osseous cranial ornaments despite repeatedly crossing this body size threshold. Our study provides novel, quantitative support for a shift in selective pressures on socio-sexual display mechanisms in theropods coincident with the evolution of pennaceous feathers. PMID:27676310

New developmental evidence clarifies the evolution of wrist bones in the dinosaur-bird transition.

PubMed

Botelho, João Francisco; Ossa-Fuentes, Luis; Soto-Acuña, Sergio; Smith-Paredes, Daniel; Nuñez-León, Daniel; Salinas-Saavedra, Miguel; Ruiz-Flores, Macarena; Vargas, Alexander O

2014-09-01

From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowing whole-mount immunofluorescence of the embryonic cartilaginous skeleton. Beyond previous controversy, we establish that the proximal-anterior ossification develops from a composite radiale+intermedium cartilage, consistent with fusion of radiale and intermedium observed in some theropod dinosaurs. Despite previous claims that the development of the distal-anterior ossification does not support the dinosaur-bird link, we found its embryonic precursor shows two distinct regions of both collagen type II and collagen type IX expression, resembling the composite semilunate bone of bird-like dinosaurs (distal carpal 1+distal carpal 2). The distal-posterior ossification develops from a cartilage referred to as "element x," but its position corresponds to distal carpal 3. The proximal-posterior ossification is perhaps most controversial: It is labelled as the ulnare in palaeontology, but we confirm the embryonic ulnare is lost during development. Re-examination of the fossil evidence reveals the ulnare was actually absent in bird-like dinosaurs. We confirm the proximal-posterior bone is a pisiform in terms of embryonic position and its development as a sesamoid associated to a tendon. However, the pisiform is absent in bird-like dinosaurs, which are known from several articulated specimens. The combined data provide compelling evidence of a remarkable evolutionary reversal: A large, ossified pisiform re-evolved in the lineage leading to birds, after a period in which it was either absent, nonossified, or very small, consistently escaping fossil preservation. The bird wrist provides a modern example of how developmental and paleontological data illuminate

Evolution of dinosaur epidermal structures.

PubMed

Barrett, Paul M; Evans, David C; Campione, Nicolás E

2015-06-01

Spectacularly preserved non-avian dinosaurs with integumentary filaments/feathers have revolutionized dinosaur studies and fostered the suggestion that the dinosaur common ancestor possessed complex integumentary structures homologous to feathers. This hypothesis has major implications for interpreting dinosaur biology, but has not been tested rigorously. Using a comprehensive database of dinosaur skin traces, we apply maximum-likelihood methods to reconstruct the phylogenetic distribution of epidermal structures and interpret their evolutionary history. Most of these analyses find no compelling evidence for the appearance of protofeathers in the dinosaur common ancestor and scales are usually recovered as the plesiomorphic state, but results are sensitive to the outgroup condition in pterosaurs. Rare occurrences of ornithischian filamentous integument might represent independent acquisitions of novel epidermal structures that are not homologous with theropod feathers. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Recent advances in lineage differentiation from stem cells: hurdles and opportunities?

PubMed Central

Terryn, Joke; Tricot, Tine; Gajjar, Madhavsai; Verfaillie, Catherine

2018-01-01

Pluripotent stem cells have the property of long-term self-renewal and the potential to give rise to descendants of the three germ layers and hence all mature cells in the human body. Therefore, they hold the promise of offering insight not only into human development but also for human disease modeling and regenerative medicine. However, the generation of mature differentiated cells that closely resemble their in vivo counterparts remains challenging. Recent advances in single-cell transcriptomics and computational modeling of gene regulatory networks are revealing a better understanding of lineage commitment and are driving modern genome editing approaches. Additional modification of the chemical microenvironment, as well as the use of bioengineering tools to recreate the cellular, extracellular matrix, and physical characteristics of the niche wherein progenitors and mature cells reside, is now being used to further improve the maturation and functionality of stem cell progeny. PMID:29552337

Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishikawa, Masaki, E-mail: masakiwestriver@gmail.com; University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343; Yanagawa, Naomi

2012-01-13

Highlights: Black-Right-Pointing-Pointer We induced renal lineages from mESCs by following the in vivo developmental cues. Black-Right-Pointing-Pointer We induced nephrogenic intermediate mesoderm by stepwise addition of factors. Black-Right-Pointing-Pointer We induced two types of renal progenitor cells by reciprocal conditioned media. Black-Right-Pointing-Pointer We propose the potential role of CD24 for the enrichment of renal lineage cells. -- Abstract: The in vitro derivation of renal lineage progenitor cells is essential for renal cell therapy and regeneration. Despite extensive studies in the past, a protocol for renal lineage induction from embryonic stem cells remains unestablished. In this study, we aimed to induce renal lineagesmore » from mouse embryonic stem cells (mESC) by following in vivo developmental stages, i.e., the induction of mesoderm (Stage I), intermediate mesoderm (Stage II) and renal lineages (Stage III). For stage I induction, in accordance with known signaling pathways involved in mesoderm development in vivo, i.e., Nodal, bone morphogenic proteins (BMPs) and Wnt, we found that the sequential addition of three factors, i.e., Activin-A (A), a surrogate for Nodal signaling, during days 0-2, A plus BMP-4 (4) during days 2-4, and A4 plus lithium (L), a surrogate for Wnt signaling, during days 4-6, was most effective to induce the mesodermal marker, Brachyury. For stage II induction, the addition of retinoic acid (R) in the continuous presence of A4L during days 6-8 was most effective to induce nephrogenic intermediate mesodermal markers, such as Pax2 and Lim1. Under this condition, more than 30% of cells were stained positive for Pax2, and there was a concomitant decrease in the expression of non-mesodermal markers. For stage III induction, in resemblance to the reciprocal induction between ureteric bud (UB) and metanephric mesenchyme (MM) during kidney development, we found that the exposure to conditioned media derived from UB and MM

An Evolutionary Cascade Model for Sauropod Dinosaur Gigantism - Overview, Update and Tests

PubMed Central

Sander, P. Martin

2013-01-01

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades (“Reproduction”, “Feeding”, “Head and neck”, “Avian-style lung”, and “Metabolism”). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait “Very high body mass”. Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size. PMID:24205267

Biology of the sauropod dinosaurs: the evolution of gigantism

PubMed Central

Sander, P Martin; Christian, Andreas; Clauss, Marcus; Fechner, Regina; Gee, Carole T; Griebeler, Eva-Maria; Gunga, Hanns-Christian; Hummel, Jürgen; Mallison, Heinrich; Perry, Steven F; Preuschoft, Holger; Rauhut, Oliver W M; Remes, Kristian; Tütken, Thomas; Wings, Oliver; Witzel, Ulrich

2011-01-01

The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism. We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores. The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates. The

Parsing Stem Cell Lineage Development Using High Content Image Analysis of Epigenetic Spatial Markers.

PubMed

Kim, Joseph J; Moghe, Prabhas V

2018-06-14

This unit describes a protocol for acquiring and analyzing high-content super-resolution images of human stem cell nuclei for the characterization and classification of the cell differentiation paths based on distinct patterns of epigenetic mark organization. Here, we describe the cell culture, immunocytochemical labeling, super-resolution imaging parameters, and MATLAB-based quantitative image analysis approaches for monitoring human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cells (hiPSCs) as the cells differentiate towards various lineages. Although this protocol uses specific cell types as examples, this approach could be easily extended to a variety of cell types and nuclear epigenetic and mechanosensitive biomarkers that are relevant to specific cell developmental scenarios. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells.

PubMed

Nakagomi, Takayuki; Kubo, Shuji; Nakano-Doi, Akiko; Sakuma, Rika; Lu, Shan; Narita, Aya; Kawahara, Maiko; Taguchi, Akihiko; Matsuyama, Tomohiro

2015-06-01

Brain vascular pericytes (PCs) are a key component of the blood-brain barrier (BBB)/neurovascular unit, along with neural and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have multipotential stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs following ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis at the site of brain injuries. © 2015 AlphaMed Press.

Paleobiology of Herbivorous Dinosaurs

NASA Astrophysics Data System (ADS)

Barrett, Paul M.

2014-05-01

Herbivorous dinosaurs were abundant, species-rich components of Late Triassic-Cretaceous terrestrial ecosystems. Obligate high-fiber herbivory evolved independently on several occasions within Dinosauria, through the intermediary step of omnivory. Anatomical character complexes associated with this diet exhibit high levels of convergence and morphological disparity, and may have evolved by correlated progression. Dinosaur faunas changed markedly during the Mesozoic, from early faunas dominated by taxa with simple, uniform feeding mechanics to Cretaceous biomes including diverse sophisticated sympatric herbivores; the environmental and biological drivers causing these changes remain unclear. Isotopic, taphonomic, and anatomical evidence implies that niche partitioning reduced competition between sympatric herbivores, via morphological differentiation, dietary preferences, and habitat selection. Large body size in dinosaur herbivores is associated with low plant productivity, and gave these animals prominent roles as ecosystem engineers. Although dinosaur herbivores lived through several major events in floral evolution, there is currently no evidence for plant-dinosaur coevolutionary interactions.

On Dinosaur Growth

NASA Astrophysics Data System (ADS)

Erickson, Gregory M.

2014-05-01

Despite nearly two centuries of investigation, a comprehensive understanding of dinosaur biology has proven intractable. The recent development of means to study tissue-level growth, age these animals, and make growth curves has revolutionized our knowledge of dinosaur lives. From such data it is now understood that dinosaurs grew both disruptively and determinately; that they rarely if ever exceeded a century in age; that they became giants through accelerated growth and dwarfed through truncated development; that they were likely endothermic, sexually matured like crocodiles, and showed survivorship like populations of large mammals; and that basal birds retained dinosaurian physiology.

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters.

PubMed

Tetteh, Paul W; Basak, Onur; Farin, Henner F; Wiebrands, Kay; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; de Sauvage, Frederic; van Es, Johan H; van Oudenaarden, Alexander; Clevers, Hans

2016-02-04

Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an Alpi-IRES-CreERT2 (Alpi(CreER)) knockin allele for lineage tracing. Marked clones consist entirely of enterocytes and are all lost from villus tips within days. Genetic fate-mapping of Alpi(+) cells before or during targeted ablation of Lgr5-expressing stem cells generated numerous long-lived crypt-villus "ribbons," indicative of dedifferentiation of enterocyte precursors into Lgr5(+) stems. By single-cell analysis of dedifferentiating enterocytes, we observed the generation of Paneth-like cells and proliferative stem cells. We conclude that the highly proliferative, short-lived enterocyte precursors serve as a large reservoir of potential stem cells during crypt regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Dinosaur fossils predict body temperatures.

PubMed

Gillooly, James F; Allen, Andrew P; Charnov, Eric L

2006-07-01

Perhaps the greatest mystery surrounding dinosaurs concerns whether they were endotherms, ectotherms, or some unique intermediate form. Here we present a model that yields estimates of dinosaur body temperature based on ontogenetic growth trajectories obtained from fossil bones. The model predicts that dinosaur body temperatures increased with body mass from approximately 25 degrees C at 12 kg to approximately 41 degrees C at 13,000 kg. The model also successfully predicts observed increases in body temperature with body mass for extant crocodiles. These results provide direct evidence that dinosaurs were reptiles that exhibited inertial homeothermy.

If Dung Beetles (Scarabaeidae: Scarabaeinae) Arose in Association with Dinosaurs, Did They Also Suffer a Mass Co-Extinction at the K-Pg Boundary?

PubMed

Gunter, Nicole L; Weir, Tom A; Slipinksi, Adam; Bocak, Ladislav; Cameron, Stephen L

2016-01-01

The evolutionary success of beetles and numerous other terrestrial insects is generally attributed to co-radiation with flowering plants but most studies have focused on herbivorous or pollinating insects. Non-herbivores represent a significant proportion of beetle diversity yet potential factors that influence their diversification have been largely unexamined. In the present study, we examine the factors driving diversification within the Scarabaeidae, a speciose beetle family with a range of both herbivorous and non-herbivorous ecologies. In particular, it has been long debated whether the key event in the evolution of dung beetles (Scarabaeidae: Scarabaeinae) was an adaptation to feeding on dinosaur or mammalian dung. Here we present molecular evidence to show that the origin of dung beetles occurred in the middle of the Cretaceous, likely in association with dinosaur dung, but more surprisingly the timing is consistent with the rise of the angiosperms. We hypothesize that the switch in dinosaur diet to incorporate more nutritious and less fibrous angiosperm foliage provided a palatable dung source that ultimately created a new niche for diversification. Given the well-accepted mass extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, we examine a potential co-extinction of dung beetles due to the loss of an important evolutionary resource, i.e., dinosaur dung. The biogeography of dung beetles is also examined to explore the previously proposed "out of Africa" hypothesis. Given the inferred age of Scarabaeinae as originating in the Lower Cretaceous, the major radiation of dung feeders prior to the Cenomanian, and the early divergence of both African and Gondwanan lineages, we hypothesise that that faunal exchange between Africa and Gondwanaland occurred during the earliest evolution of the Scarabaeinae. Therefore we propose that both Gondwanan vicariance and dispersal of African lineages is responsible for present day distribution of

If Dung Beetles (Scarabaeidae: Scarabaeinae) Arose in Association with Dinosaurs, Did They Also Suffer a Mass Co-Extinction at the K-Pg Boundary?

PubMed Central

Gunter, Nicole L.; Weir, Tom A.; Cameron, Stephen L.

2016-01-01

The evolutionary success of beetles and numerous other terrestrial insects is generally attributed to co-radiation with flowering plants but most studies have focused on herbivorous or pollinating insects. Non-herbivores represent a significant proportion of beetle diversity yet potential factors that influence their diversification have been largely unexamined. In the present study, we examine the factors driving diversification within the Scarabaeidae, a speciose beetle family with a range of both herbivorous and non-herbivorous ecologies. In particular, it has been long debated whether the key event in the evolution of dung beetles (Scarabaeidae: Scarabaeinae) was an adaptation to feeding on dinosaur or mammalian dung. Here we present molecular evidence to show that the origin of dung beetles occurred in the middle of the Cretaceous, likely in association with dinosaur dung, but more surprisingly the timing is consistent with the rise of the angiosperms. We hypothesize that the switch in dinosaur diet to incorporate more nutritious and less fibrous angiosperm foliage provided a palatable dung source that ultimately created a new niche for diversification. Given the well-accepted mass extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, we examine a potential co-extinction of dung beetles due to the loss of an important evolutionary resource, i.e., dinosaur dung. The biogeography of dung beetles is also examined to explore the previously proposed “out of Africa” hypothesis. Given the inferred age of Scarabaeinae as originating in the Lower Cretaceous, the major radiation of dung feeders prior to the Cenomanian, and the early divergence of both African and Gondwanan lineages, we hypothesise that that faunal exchange between Africa and Gondwanaland occurred during the earliest evolution of the Scarabaeinae. Therefore we propose that both Gondwanan vicariance and dispersal of African lineages is responsible for present day distribution of

Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro potential, and Genome‐wide expression analysis

PubMed Central

Sirko, Swetlana; Beckers, Johannes; Irmler, Martin

2015-01-01

Here, we review the stem cell hallmarks of endogenous neural stem cells (NSCs) during development and in some niches of the adult mammalian brain to then compare these with reactive astrocytes acquiring stem cell hallmarks after traumatic and ischemic brain injury. Notably, even endogenous NSCs including the earliest NSCs, the neuroepithelial cells, generate in most cases only a single type of progeny and self‐renew only for a rather short time in vivo. In vitro, however, especially cells cultured under neurosphere conditions reveal a larger potential and long‐term self‐renewal under the influence of growth factors. This is rather well comparable to reactive astrocytes in the traumatic or ischemic brain some of which acquire neurosphere‐forming capacity including multipotency and long‐term self‐renewal in vitro, while they remain within their astrocyte lineage in vivo. Both reactive astrocytes and endogenous NSCs exhibit stem cell hallmarks largely in vitro, but their lineage differs in vivo. Both populations generate largely a single cell type in vivo, but endogenous NSCs generate neurons and reactive astrocytes remain in the astrocyte lineage. However, at some early postnatal stages or in some brain regions reactive astrocytes can be released from this fate restriction, demonstrating that they can also enact neurogenesis. Thus, reactive astrocytes and NSCs share many characteristic hallmarks, but also exhibit key differences. This conclusion is further substantiated by genome‐wide expression analysis comparing NSCs at different stages with astrocytes from the intact and injured brain parenchyma. GLIA 2015;63:1452–1468 PMID:25965557

The extinction of the dinosaurs.

PubMed

Brusatte, Stephen L; Butler, Richard J; Barrett, Paul M; Carrano, Matthew T; Evans, David C; Lloyd, Graeme T; Mannion, Philip D; Norell, Mark A; Peppe, Daniel J; Upchurch, Paul; Williamson, Thomas E

2015-05-01

Non-avian dinosaurs went extinct 66 million years ago, geologically coincident with the impact of a large bolide (comet or asteroid) during an interval of massive volcanic eruptions and changes in temperature and sea level. There has long been fervent debate about how these events affected dinosaurs. We review a wealth of new data accumulated over the past two decades, provide updated and novel analyses of long-term dinosaur diversity trends during the latest Cretaceous, and discuss an emerging consensus on the extinction's tempo and causes. Little support exists for a global, long-term decline across non-avian dinosaur diversity prior to their extinction at the end of the Cretaceous. However, restructuring of latest Cretaceous dinosaur faunas in North America led to reduced diversity of large-bodied herbivores, perhaps making communities more susceptible to cascading extinctions. The abruptness of the dinosaur extinction suggests a key role for the bolide impact, although the coarseness of the fossil record makes testing the effects of Deccan volcanism difficult. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

A Child Centered Approach to Dinosaurs.

ERIC Educational Resources Information Center

Strader, William H.; Rinker, Catherine A.

1989-01-01

Describes a curriculum for teaching young children about dinosaurs. Activity topics included Diplodocus eggs, sorting dinosaurs, creating terrariums, and extinction. Describes the incorporation of dinosaur activities into other subject areas and resource materials. (RJC)

Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis

PubMed Central

Chapple, Richard H.; Tseng, Yu-Jung; Hu, Tianyuan; Kitano, Ayumi; Takeichi, Makiko; Hoegenauer, Kevin A.

2018-01-01

Characterization of hematopoietic stem cells (HSCs) has advanced largely owing to transplantation assays, in which the developmental potential of HSCs is assessed generally in nonhomeostatic conditions. These studies established that adult HSCs extensively contribute to multilineage hematopoietic regeneration upon transplantation. On the contrary, recent studies performing lineage tracing of HSCs under homeostatic conditions have shown that adult HSCs may contribute far less to steady-state hematopoiesis than would be anticipated based on transplantation assays. Here, we used 2 independent HSC-lineage–tracing models to examine the contribution of adult HSCs to steady-state hematopoiesis. We show that adult HSCs contribute robustly to steady-state hematopoiesis, exhibiting faster efflux toward the myeloid lineages compared with lymphoid lineages. Platelets were robustly labeled by HSCs, reaching the same level of labeling as HSCs by 1 year of chase. Our results support the view that adult HSCs contribute to the continuous influx of blood cells during steady-state hematopoiesis. PMID:29848758

Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages.

PubMed

Arsic, Nikola; Mamaeva, Daria; Lamb, Ned J; Fernandez, Anne

2008-04-01

Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal beta III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders.

Brushing up on Dinosaurs.

ERIC Educational Resources Information Center

Weisburd, Stefi

1986-01-01

Describes new methods of reconstruction of dinosaurs using skeletons, mummified skin, and muscle scars, along with clay and paint. Examines some inaccuracies in dinosaur's physical characteristics and behaviors suggested by recent findings. (TW)

Dinosaur Fossils Predict Body Temperatures

PubMed Central

Allen, Andrew P; Charnov, Eric L

2006-01-01

Perhaps the greatest mystery surrounding dinosaurs concerns whether they were endotherms, ectotherms, or some unique intermediate form. Here we present a model that yields estimates of dinosaur body temperature based on ontogenetic growth trajectories obtained from fossil bones. The model predicts that dinosaur body temperatures increased with body mass from approximately 25 °C at 12 kg to approximately 41 °C at 13,000 kg. The model also successfully predicts observed increases in body temperature with body mass for extant crocodiles. These results provide direct evidence that dinosaurs were reptiles that exhibited inertial homeothermy. PMID:16817695

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

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.

Biology of the sauropod dinosaurs: the evolution of gigantism.

PubMed

Sander, P Martin; Christian, Andreas; Clauss, Marcus; Fechner, Regina; Gee, Carole T; Griebeler, Eva-Maria; Gunga, Hanns-Christian; Hummel, Jürgen; Mallison, Heinrich; Perry, Steven F; Preuschoft, Holger; Rauhut, Oliver W M; Remes, Kristian; Tütken, Thomas; Wings, Oliver; Witzel, Ulrich

2011-02-01

The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism. We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores. The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates. The

Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, Paik Wah; Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur; Abdul Hamid, Zariyantey, E-mail: zyantey@ukm.edu.my

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24 h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-formingmore » unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e{sup +} cells but reduced the total counts of Sca-1{sup +}, CD11b{sup +}, Gr-1{sup +}, and CD45{sup +} cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5 μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12 μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage. - Highlights: • We examine 1,4-BQ toxicity targeting mouse hematopoietic cell lineages. • 1,4-BQ induces concentration-dependent cytotoxicity in bone marrow (BM) cells. • 1,4-BQ shows lineage-related toxicity on hematopoietic stem and

A new hypothesis of dinosaur relationships and early dinosaur evolution.

PubMed

Baron, Matthew G; Norman, David B; Barrett, Paul M

2017-03-22

For 130 years, dinosaurs have been divided into two distinct clades-Ornithischia and Saurischia. Here we present a hypothesis for the phylogenetic relationships of the major dinosaurian groups that challenges the current consensus concerning early dinosaur evolution and highlights problematic aspects of current cladistic definitions. Our study has found a sister-group relationship between Ornithischia and Theropoda (united in the new clade Ornithoscelida), with Sauropodomorpha and Herrerasauridae (as the redefined Saurischia) forming its monophyletic outgroup. This new tree topology requires redefinition and rediagnosis of Dinosauria and the subsidiary dinosaurian clades. In addition, it forces re-evaluations of early dinosaur cladogenesis and character evolution, suggests that hypercarnivory was acquired independently in herrerasaurids and theropods, and offers an explanation for many of the anatomical features previously regarded as notable convergences between theropods and early ornithischians.

Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

PubMed

Song, Min Jae; Dean, David; Knothe Tate, Melissa L

2013-07-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Evolution and Extinction of the Dinosaurs

NASA Astrophysics Data System (ADS)

Fastovsky, David E.; Weishampel, David B.

2005-02-01

Written for non-specialists, this detailed survey of dinosaur origins, diversity, and extinction is designed as a series of successive essays covering important and timely topics in dinosaur paleobiology, such as "warm-bloodedness," birds as living dinosaurs, the new, non-flying feathered dinosaurs, dinosaur functional morphology, and cladistic methods in systematics. Its explicitly phylogenetic approach to the group is that taken by dinosaur specialists. The book is not an edited compilation of the works of many individuals, but a unique, cohesive perspective on Dinosauria. Lavishly illustrated with hundreds of new, specially commissioned illustrations by John Sibbick, world-famous illustrator of dinosaurs, the volume includes multi-page drawings as well as sketches and diagrams. First edition Hb (1996): 0-521-44496-9 David E. Fastovsky is Professor of Geosciences at the University of Rhode Island. Fastovsky, the author of numerous scientific publications dealing with Mesozoic vertebrate faunas and their ancient environments, is also scientific co-Editor of Geology. He has undertaken extensive fieldwork studying dinosaurs and their environments in Montana, North Dakota, Arizona, Mexico, and Mongolia. David B. Weishampel is a professor at the Center for Functional Anatomy and Evolution at Johns Hopkins University, School of Medicine. Weishampel is best known for discovering, researching, and naming several rare European dinosaur species. During the 1980s Weishampel gained fame for his work with American paleontologist Jack Horner and later named the famous plant-eating, egg-laying Orodromeus, Horner. Now, a decade after his pioneering studies with Horner, Weishampel is most widely known for his current work on the Romanian dinosaur fauna. He is the author and co-author of many titles, including The Dinosaur Papers, 1676-1906 (Norton, 2003); The Dinosauria, (University of California, 1990); and Dinosaurs of the East Coast, (Johns Hopkins University Press, 1996).

Dinosaur Reproduction and Parenting

NASA Astrophysics Data System (ADS)

Horner, John R.

Non-avian dinosaur reproductive and parenting behaviors were mostly similar to those of extant archosaurs. Non-avian dinosaurs were probably sexually dimorphic and some may have engaged in hierarchical rituals. Non-avian coelurosaurs (e.g. Troodontidae, Oviraptorosauria) had two active oviducts, each of which produced single eggs on a daily or greater time scale. The eggs of non-coelurosaurian dinosaurs (e.g. Ornithischia, Sauropoda) were incubated in soils, whereas the eggs of non-avian coelurosaurs (e.g. Troodon, Oviraptor) were incubated with a combination of soil and direct parental contact. Parental attention to the young was variable, ranging from protection from predators to possible parental feeding of nest-bound hatchlings. Semi-altricial hadrosaur hatchlings exited their respective nests near the time of their first linear doubling. Some reproductive behaviors, once thought exclusive to Aves, arose first in non-avian dinosaurs. The success of the Dinosauria may be related to reproductive strategies.

Simulating Dinosaur Digestion in the Classroom.

ERIC Educational Resources Information Center

Peczkis, Jan

1992-01-01

Describes an activity for use with a chapter on dinosaurs, prehistoric life, or digestion in which children make simulated dinosaur stomachs to gain hands-on experience about the theory of gastroliths, or stomach stones. Presents teacher information about the digestive processes in birds and dinosaurs. Discusses materials needed, objectives,…

Cell lineages of the embryo of the nematode Caenorhabditis elegans.

PubMed

Deppe, U; Schierenberg, E; Cole, T; Krieg, C; Schmitt, D; Yoder, B; von Ehrenstein, G

1978-01-01

Embryogenesis of the free-living soil nematode Caenorhabditis elegans produces a juvenile having about 550 cells at hatching. We have determined the lineages of 182 cells by tracing the divisions of individual cells in living embryos. An invariant pattern of cleavage divisions of the egg generates a set of stem cells. These stem cells are the founders of six stem cell lineages. Each lineage has its own clock--i.e., an autonomous rhythm of synchronous cell divisions. The rhythms are maintained in spite of extensive cellular rearrangement. The rate and the orientation of the cell divisions of the cell lineages are essentially invariant among individuals. Thus, the destiny of cells seems to depend primarily on their lineage history. The anterior position of the site of origin of the stem cells in the egg relates to the rate of the cell cycle clock, suggesting intracellular preprogramming of the uncleaved egg. We used a technique that allows normal embryogenesis, from the fertilized egg to hatching, outside the parent under a cover glass. Embryogenesis was followed microscopically with Nomarski interference optics and high-resolution video recording.

Geochemical and mineralogical studies of dinosaur bone from the Morrison Formation at Dinosaur Ridge

USGS Publications Warehouse

Modreski, P.J.

2001-01-01

The dinosaur bones first discovered in 1877 in the Upper Jurassic Morrison Formation at Morrison, Colorado were the first major find of dinosaur skeletons in the western U.S. and led to the recognition of four new dinosaur genera (Apatosaurus, Allosaurus, Diplodocus, and Stegosaurus). Eight articles dealing with these bones which appeared as research reports in the annual reports of the Friends of Dinosaur Ridge from 1990-1999 are condensed and summarized with some additional comments. Two of the articles are about the mineralogy and preservation of the bones; two are about the physical description of the bone occurrence; two are about the history of the site, and two are about use of novel instrumental methods (ground-penetrating radar and a directional scintillometer) to search for new bones.

What lies beneath: sub-articular long bone shape scaling in eutherian mammals and saurischian dinosaurs suggests different locomotor adaptations for gigantism.

PubMed

Bonnan, Matthew F; Wilhite, D Ray; Masters, Simon L; Yates, Adam M; Gardner, Christine K; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load.

What Lies Beneath: Sub-Articular Long Bone Shape Scaling in Eutherian Mammals and Saurischian Dinosaurs Suggests Different Locomotor Adaptations for Gigantism

PubMed Central

Bonnan, Matthew F.; Wilhite, D. Ray; Masters, Simon L.; Yates, Adam M.; Gardner, Christine K.; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load. PMID:24130690

Consumption of crustaceans by megaherbivorous dinosaurs: dietary flexibility and dinosaur life history strategies.

PubMed

Chin, Karen; Feldmann, Rodney M; Tashman, Jessica N

2017-09-21

Large plant-eating dinosaurs are usually presumed to have been strictly herbivorous, because their derived teeth and jaws were capable of processing fibrous plant foods. This inferred feeding behavior offers a generalized view of dinosaur food habits, but rare direct fossil evidence of diet provides more nuanced insights into feeding behavior. Here we describe fossilized feces (coprolites) that demonstrate recurring consumption of crustaceans and rotted wood by large Late Cretaceous dinosaurs. These multi-liter coprolites from the Kaiparowits Formation are primarily composed of comminuted conifer wood tissues that were fungally degraded before ingestion. Thick fragments of laminar crustacean cuticle are scattered within the coprolite contents and suggest that the dinosaurian defecators consumed sizeable crustaceans that sheltered in rotting logs. The diet of decayed wood and crustaceans offered a substantial supply of plant polysaccharides, with added dividends of animal protein and calcium. Nevertheless, it is unlikely that the fossilized fecal residues depict year-round feeding habits. It is more reasonable to infer that these coprolites reflected seasonal dietary shifts-possibly related to the dinosaurs' oviparous breeding activities. This surprising fossil evidence challenges conventional notions of herbivorous dinosaur diets and reveals a degree of dietary flexibility that is consistent with that of extant herbivorous birds.

Metabolism of dinosaurs as determined from their growth.

PubMed

Lee, Scott A

2015-09-01

A model based on cellular properties is used to analyze the mass growth curves of 20 dinosaurs. This analysis yields the first measurement of the average cellular metabolism of dinosaurs. The organismal metabolism is also determined. The cellular metabolism of dinosaurs is found to decrease with mass at a slower rate than is observed in extant animals. The organismal metabolism increases with the mass of the dinosaur. These results come from both the Saurischia and Ornithischia branches of Dinosauria, suggesting that the observed metabolic features were common to all dinosaurs. The results from dinosaurs are compared to data from extant placental and marsupial mammals, a monotreme, and altricial and precocial birds, reptiles, and fish. Dinosaurs had cellular and organismal metabolisms in the range observed in extant mesotherms.

Metabolism of dinosaurs as determined from their growth

NASA Astrophysics Data System (ADS)

Lee, Scott A.

2015-09-01

A model based on cellular properties is used to analyze the mass growth curves of 20 dinosaurs. This analysis yields the first measurement of the average cellular metabolism of dinosaurs. The organismal metabolism is also determined. The cellular metabolism of dinosaurs is found to decrease with mass at a slower rate than is observed in extant animals. The organismal metabolism increases with the mass of the dinosaur. These results come from both the Saurischia and Ornithischia branches of Dinosauria, suggesting that the observed metabolic features were common to all dinosaurs. The results from dinosaurs are compared to data from extant placental and marsupial mammals, a monotreme, and altricial and precocial birds, reptiles, and fish. Dinosaurs had cellular and organismal metabolisms in the range observed in extant mesotherms.

Body size distribution of the dinosaurs.

PubMed

O'Gorman, Eoin J; Hone, David W E

2012-01-01

The distribution of species body size is critically important for determining resource use within a group or clade. It is widely known that non-avian dinosaurs were the largest creatures to roam the Earth. There is, however, little understanding of how maximum species body size was distributed among the dinosaurs. Do they share a similar distribution to modern day vertebrate groups in spite of their large size, or did they exhibit fundamentally different distributions due to unique evolutionary pressures and adaptations? Here, we address this question by comparing the distribution of maximum species body size for dinosaurs to an extensive set of extant and extinct vertebrate groups. We also examine the body size distribution of dinosaurs by various sub-groups, time periods and formations. We find that dinosaurs exhibit a strong skew towards larger species, in direct contrast to modern day vertebrates. This pattern is not solely an artefact of bias in the fossil record, as demonstrated by contrasting distributions in two major extinct groups and supports the hypothesis that dinosaurs exhibited a fundamentally different life history strategy to other terrestrial vertebrates. A disparity in the size distribution of the herbivorous Ornithischia and Sauropodomorpha and the largely carnivorous Theropoda suggests that this pattern may have been a product of a divergence in evolutionary strategies: herbivorous dinosaurs rapidly evolved large size to escape predation by carnivores and maximise digestive efficiency; carnivores had sufficient resources among juvenile dinosaurs and non-dinosaurian prey to achieve optimal success at smaller body size.

Body Size Distribution of the Dinosaurs

PubMed Central

O’Gorman, Eoin J.; Hone, David W. E.

2012-01-01

The distribution of species body size is critically important for determining resource use within a group or clade. It is widely known that non-avian dinosaurs were the largest creatures to roam the Earth. There is, however, little understanding of how maximum species body size was distributed among the dinosaurs. Do they share a similar distribution to modern day vertebrate groups in spite of their large size, or did they exhibit fundamentally different distributions due to unique evolutionary pressures and adaptations? Here, we address this question by comparing the distribution of maximum species body size for dinosaurs to an extensive set of extant and extinct vertebrate groups. We also examine the body size distribution of dinosaurs by various sub-groups, time periods and formations. We find that dinosaurs exhibit a strong skew towards larger species, in direct contrast to modern day vertebrates. This pattern is not solely an artefact of bias in the fossil record, as demonstrated by contrasting distributions in two major extinct groups and supports the hypothesis that dinosaurs exhibited a fundamentally different life history strategy to other terrestrial vertebrates. A disparity in the size distribution of the herbivorous Ornithischia and Sauropodomorpha and the largely carnivorous Theropoda suggests that this pattern may have been a product of a divergence in evolutionary strategies: herbivorous dinosaurs rapidly evolved large size to escape predation by carnivores and maximise digestive efficiency; carnivores had sufficient resources among juvenile dinosaurs and non-dinosaurian prey to achieve optimal success at smaller body size. PMID:23284818

Dinosaurs in the year of Darwin.

PubMed

Dodson, Peter

2009-09-01

This special issue of The Anatomical Record explores the recent advances in the functional morphology and paleobiology of dinosaurs. Although Darwin did not study dinosaurs because paleontology was in its infancy a century and half ago, he considered both paleontology and anatomy as essential subjects for establishing the validity of evolution. The study of dinosaurs constitutes a vigorous subdiscipline within vertebrate paleontology, and anatomists and evolutionary functional morphologists constitute an especially creative subgroup within dinosaur paleontology. The collection of 17 papers presented in this issue encompass cranial anatomy, postcranial anatomy, and paleobiology of dinosaurs and other archosaurs. Soft tissue subjects include studies of brain structure, jaw adductor muscles, and keratinous appendages of the skull. Taxonomically, it includes four papers with a focus on theropods, including Tyrannosaurus, five papers dealing with ceratopsians, three papers on hadrosaurs, and one on ankylosaurs. Modern anatomical techniques such as CT scanning, finite element analysis, and high resolution histology are emphasized. The visual presentation of results of these studies is spectacular. Results include the first-ever life history table of a plant-eating dinosaur; a determination of the head orientation of Tyrannosaurus and its relatives based on interpretation of the semicircular canals. The claws of Velociraptor appear to best adapted for tree climbing, but not for horrific predatory activities. Pachyrhinosaurus evidently used its massive head for head butting. The tail club of the armored dinosaur Euoplocephalus had the structural integrity to be used as a weapon. The pages abound with insights such as these. Dinosaurs once dead for millions of years live again! (c) 2009 Wiley-Liss, Inc.

Ancestral trees for modeling stem cell lineages genetically rather than functionally: understanding mutation accumulation and distinguishing the restrictive cancer stem cell propagation theory and the unrestricted cell propagation theory of human tumorigenesis.

PubMed

Shibata, Darryl K; Kern, Scott E

2008-01-01

Cancer stem cells either could be rare or common in tumors, constituting the major distinction between the two fundamentally opposed theoretical models of tumor progression: A newer and restrictive stem cell propagation model, in which the stem cells are a small and special minority of the tumor cells, and a standard older model, an unrestricted cell proliferation theory, in which many or most tumor cells are capable of indefinite generations of cell division. Stem cells of tumors are difficult to quantitate using functional assays, and the validity of the most common assays is seriously questioned. Nonetheless, stem cells are an essential component of any tumorigenesis model. Alternative approaches to studying tumor stem cells should be explored. Cell populations can be conceived of as having a genealogy, a relationship of cells to their ancestral lineage, from the zygote to the adult cells or neoplasms. Models using ancestral trees thus offer an anatomic and genetic means to "observe" stem cells independent of artificial conditions. Ancestral trees broaden our attention backward along a lineage, to the zygote stage, and thereby add insight into how the mutations of tumors accumulate. It is possible that a large fraction of mutations in a tumor originate from normal, endogenous, replication errors (nearly all being passenger mutations) occurring prior to the emergence of the first transformed cell. Trees can be constructed from experimental measurements - molecular clocks - of real human tissues and tumors. Detailed analysis of single-cell methylation patterns, heritable yet slightly plastic, now can provide this information in the necessary depth. Trees based on observations of molecular clocks may help us to distinguish between competing theories regarding the proliferative properties among cells of actual human tumors, to observe subtle and difficult phenomena such as the extinction of stem lineages, and to address the origins and rates of mutations in various

Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via re-specification of lineage-restricted precursors

PubMed Central

Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Li, Hu; Hadland, Brandon K.; Bernstein, Irwin D.; Collins, James J.; Zon, Leonard I.; Daley, George Q.

2013-01-01

Summary Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor (HSPCs) has limited their characterization to in vitro assays. We report a strategy to re-specify lineage-restricted CD34+CD45+ myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engraft in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34+CD38− cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, were required for engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription factor-mediated engraftment of blood progenitors from human pluripotent cells. PMID:24094326

Lineage-tracking of stem cell differentiation: a neutral model of hematopoiesis in rhesus macaque

NASA Astrophysics Data System (ADS)

Chou, Tom

How a potentially diverse population of hematopoietic stem cells (HSCs) differentiates and proliferates to supply more than 1011 mature blood cells every day in humans remains a key biological question. We investigated this process by quantitatively analyzing the clonal structure of peripheral blood that is generated by a population of transplanted lentivirus-marked HSCs in myeloablated rhesus macaques. Each transplanted HSC generates a clonal lineage of cells in the peripheral blood that is then detected and quantified through deep sequencing of the viral vector integration sites (VIS) common within each lineage. This approach allowed us to observe, over a period of 4-12 years, hundreds of distinct clonal lineages. Surprisingly, while the distinct clone sizes varied by three orders of magnitude, we found that collectively, they form a steady-state clone size-distribution with a distinctive shape. Our concise model shows that slow HSC differentiation followed by fast progenitor growth is responsible for the observed broad clone size-distribution. Although all cells are assumed to be statistically identical, analogous to a neutral theory for the different clone lineages, our mathematical approach captures the intrinsic variability in the times to HSC differentiation after transplantation. Steady-state solutions of our model show that the predicted clone size-distribution is sensitive to only two combinations of parameters. By fitting the measured clone size-distributions to our mechanistic model, we estimate both the effective HSC differentiation rate and the number of active HSCs. NSF and NIH.

The precise temporal calibration of dinosaur origins

PubMed Central

Marsicano, Claudia A.; Irmis, Randall B.; Mancuso, Adriana C.; Mundil, Roland; Chemale, Farid

2016-01-01

Dinosaurs have been major components of ecosystems for over 200 million years. Although different macroevolutionary scenarios exist to explain the Triassic origin and subsequent rise to dominance of dinosaurs and their closest relatives (dinosauromorphs), all lack critical support from a precise biostratigraphically independent temporal framework. The absence of robust geochronologic age control for comparing alternative scenarios makes it impossible to determine if observed faunal differences vary across time, space, or a combination of both. To better constrain the origin of dinosaurs, we produced radioisotopic ages for the Argentinian Chañares Formation, which preserves a quintessential assemblage of dinosaurian precursors (early dinosauromorphs) just before the first dinosaurs. Our new high-precision chemical abrasion thermal ionization mass spectrometry (CA-TIMS) U–Pb zircon ages reveal that the assemblage is early Carnian (early Late Triassic), 5- to 10-Ma younger than previously thought. Combined with other geochronologic data from the same basin, we constrain the rate of dinosaur origins, demonstrating their relatively rapid origin in a less than 5-Ma interval, thus halving the temporal gap between assemblages containing only dinosaur precursors and those with early dinosaurs. After their origin, dinosaurs only gradually dominated mid- to high-latitude terrestrial ecosystems millions of years later, closer to the Triassic–Jurassic boundary. PMID:26644579

The precise temporal calibration of dinosaur origins.

PubMed

Marsicano, Claudia A; Irmis, Randall B; Mancuso, Adriana C; Mundil, Roland; Chemale, Farid

2016-01-19

Dinosaurs have been major components of ecosystems for over 200 million years. Although different macroevolutionary scenarios exist to explain the Triassic origin and subsequent rise to dominance of dinosaurs and their closest relatives (dinosauromorphs), all lack critical support from a precise biostratigraphically independent temporal framework. The absence of robust geochronologic age control for comparing alternative scenarios makes it impossible to determine if observed faunal differences vary across time, space, or a combination of both. To better constrain the origin of dinosaurs, we produced radioisotopic ages for the Argentinian Chañares Formation, which preserves a quintessential assemblage of dinosaurian precursors (early dinosauromorphs) just before the first dinosaurs. Our new high-precision chemical abrasion thermal ionization mass spectrometry (CA-TIMS) U-Pb zircon ages reveal that the assemblage is early Carnian (early Late Triassic), 5- to 10-Ma younger than previously thought. Combined with other geochronologic data from the same basin, we constrain the rate of dinosaur origins, demonstrating their relatively rapid origin in a less than 5-Ma interval, thus halving the temporal gap between assemblages containing only dinosaur precursors and those with early dinosaurs. After their origin, dinosaurs only gradually dominated mid- to high-latitude terrestrial ecosystems millions of years later, closer to the Triassic-Jurassic boundary.

Multipotent Caudal Neural Progenitors Derived from Human Pluripotent Stem Cells That Give Rise to Lineages of the Central and Peripheral Nervous System

PubMed Central

Hasegawa, Kouichi; Menheniott, Trevelyan; Rollo, Ben; Zhang, Dongcheng; Hough, Shelley; Alshawaf, Abdullah; Febbraro, Fabia; Ighaniyan, Samiramis; Leung, Jessie; Elliott, David A.; Newgreen, Donald F.; Pera, Martin F.

2015-01-01

Abstract The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named “caudal neural progenitors” (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube. Stem Cells 2015;33:1759–1770 PMID:25753817

Defined three-dimensional culture conditions mediate efficient induction of definitive endoderm lineage from human umbilical cord Wharton's jelly mesenchymal stem cells.

PubMed

Al Madhoun, Ashraf; Ali, Hamad; AlKandari, Sarah; Atizado, Valerie Lopez; Akhter, Nadeem; Al-Mulla, Fahd; Atari, Maher

2016-11-16

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are gaining increasing interest as an alternative source of stem cells for regenerative medicine applications. Definitive endoderm (DE) specification is a prerequisite for the development of vital organs such as liver and pancreas. Hence, efficient induction of the DE lineage from stem cells is crucial for subsequent generation of clinically relevant cell types. Here we present a defined 3D differentiation protocol of WJ-MSCs into DE cells. WJ-MSCs were cultured in suspension to generate spheroids, about 1500 cells each, for 7 days. The serum-free differentiation media contained specific growth factors, cytokines, and small molecules that specifically regulate signaling pathways including sonic hedgehog, bone morphogenetic protein, Activin/Wnt, and Notch. We obtained more than 85 % DE cells as shown with FACS analysis using antibodies directed against the DE marker CXCR4. In addition, biochemical and molecular analysis of bona-fide DE markers revealed a time-course induction of Sox17, CXCR4, and FoxA2. Focused PCR-based array also indicated a specific induction into the DE lineage. In this study, we report an efficient serum-free protocol to differentiate WJ-MSCs into DE cells utilizing 3D spheroid formation. Our approach might aid in the development of new protocols to obtain DE-derivative lineages including liver-like and pancreatic insulin-producing cells.

Theory and Practice of Lineage Tracing.

PubMed

Hsu, Ya-Chieh

2015-11-01

Lineage tracing is a method that delineates all progeny produced by a single cell or a group of cells. The possibility of performing lineage tracing initiated the field of Developmental Biology and continues to revolutionize Stem Cell Biology. Here, I introduce the principles behind a successful lineage-tracing experiment. In addition, I summarize and compare different methods for conducting lineage tracing and provide examples of how these strategies can be implemented to answer fundamental questions in development and regeneration. The advantages and limitations of each method are also discussed. © 2015 AlphaMed Press.

Avian-like breathing mechanics in maniraptoran dinosaurs

PubMed Central

Codd, Jonathan R; Manning, Phillip L; Norell, Mark A; Perry, Steven F

2007-01-01

In 1868 Thomas Huxley first proposed that dinosaurs were the direct ancestors of birds and subsequent analyses have identified a suite of ‘avian’ characteristics in theropod dinosaurs. Ossified uncinate processes are found in most species of extant birds and also occur in extinct non-avian maniraptoran dinosaurs. Their presence in these dinosaurs represents another morphological character linking them to Aves, and further supports the presence of an avian-like air-sac respiratory system in theropod dinosaurs, prior to the evolution of flight. Here we report a phylogenetic analysis of the presence of uncinate processes in Aves and non-avian maniraptoran dinosaurs indicating that these were homologous structures. Furthermore, recent work on Canada geese has demonstrated that uncinate processes are integral to the mechanics of avian ventilation, facilitating both inspiration and expiration. In extant birds, uncinate processes function to increase the mechanical advantage for movements of the ribs and sternum during respiration. Our study presents a mechanism whereby uncinate processes, in conjunction with lateral and ventral movements of the sternum and gastral basket, affected avian-like breathing mechanics in extinct non-avian maniraptoran dinosaurs. PMID:17986432

Adaptive radiation of multituberculate mammals before the extinction of dinosaurs.

PubMed

Wilson, Gregory P; Evans, Alistair R; Corfe, Ian J; Smits, Peter D; Fortelius, Mikael; Jernvall, Jukka

2012-03-14

The Cretaceous-Paleogene mass extinction approximately 66 million years ago is conventionally thought to have been a turning point in mammalian evolution. Prior to that event and for the first two-thirds of their evolutionary history, mammals were mostly confined to roles as generalized, small-bodied, nocturnal insectivores, presumably under selection pressures from dinosaurs. Release from these pressures, by extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, triggered ecological diversification of mammals. Although recent individual fossil discoveries have shown that some mammalian lineages diversified ecologically during the Mesozoic era, comprehensive ecological analyses of mammalian groups crossing the Cretaceous-Paleogene boundary are lacking. Such analyses are needed because diversification analyses of living taxa allow only indirect inferences of past ecosystems. Here we show that in arguably the most evolutionarily successful clade of Mesozoic mammals, the Multituberculata, an adaptive radiation began at least 20 million years before the extinction of non-avian dinosaurs and continued across the Cretaceous-Paleogene boundary. Disparity in dental complexity, which relates to the range of diets, rose sharply in step with generic richness and disparity in body size. Moreover, maximum dental complexity and body size demonstrate an adaptive shift towards increased herbivory. This dietary expansion tracked the ecological rise of angiosperms and suggests that the resources that were available to multituberculates were relatively unaffected by the Cretaceous-Paleogene mass extinction. Taken together, our results indicate that mammals were able to take advantage of new ecological opportunities in the Mesozoic and that at least some of these opportunities persisted through the Cretaceous-Paleogene mass extinction. Similar broad-scale ecomorphological inventories of other radiations may help to constrain the possible causes of mass extinctions.

Dinosaur biomechanics

PubMed Central

Alexander, R. McNeill

2006-01-01

Biomechanics has made large contributions to dinosaur biology. It has enabled us to estimate both the speeds at which dinosaurs generally moved and the maximum speeds of which they may have been capable. It has told us about the range of postures they could have adopted, for locomotion and for feeding, and about the problems of blood circulation in sauropods with very long necks. It has made it possible to calculate the bite forces of predators such as Tyrannosaurus, and the stresses they imposed on its skull; and to work out the remarkable chewing mechanism of hadrosaurs. It has shown us how some dinosaurs may have produced sounds. It has enabled us to estimate the effectiveness of weapons such as the tail spines of Stegosaurus. In recent years, techniques such as computational tomography and finite element analysis, and advances in computer modelling, have brought new opportunities. Biomechanists should, however, be especially cautious in their work on animals known only as fossils. The lack of living specimens and even soft tissues oblige us to make many assumptions. It is important to be aware of the often wide ranges of uncertainty that result. PMID:16822743

Directing lineage specification of human mesenchymal stem cells by decoupling electrical stimulation and physical patterning on unmodified graphene

NASA Astrophysics Data System (ADS)

Balikov, Daniel A.; Fang, Brian; Chun, Young Wook; Crowder, Spencer W.; Prasai, Dhiraj; Lee, Jung Bok; Bolotin, Kiril I.; Sung, Hak-Joon

2016-07-01

The organization and composition of the extracellular matrix (ECM) have been shown to impact the propagation of electrical signals in multiple tissue types. To date, many studies with electroactive biomaterial substrates have relied upon passive electrical stimulation of the ionic media to affect cell behavior. However, development of cell culture systems in which stimulation can be directly applied to the material - thereby isolating the signal to the cell-material interface and cell-cell contracts - would provide a more physiologically-relevant paradigm for investigating how electrical cues modulate lineage-specific stem cell differentiation. In the present study, we have employed unmodified, directly-stimulated, (un)patterned graphene as a cell culture substrate to investigate how extrinsic electrical cycling influences the differentiation of naïve human mesenchymal stem cells (hMSCs) without the bias of exogenous biochemicals. We first demonstrated that cyclic stimulation does not deteriorate the cell culture media or result in cytotoxic pH, which are critical experiments for correct interpretation of changes in cell behavior. We then measured how the expression of osteogenic and neurogenic lineage-specific markers were altered simply by exposure to electrical stimulation and/or physical patterns. Expression of the early osteogenic transcription factor RUNX2 was increased by electrical stimulation on all graphene substrates, but the mature marker osteopontin was only modulated when stimulation was combined with physical patterns. In contrast, the expression of the neurogenic markers MAP2 and β3-tubulin were enhanced in all electrical stimulation conditions, and were less responsive to the presence of patterns. These data indicate that specific combinations of non-biological inputs - material type, electrical stimulation, physical patterns - can regulate hMSC lineage specification. This study represents a substantial step in understanding how the interplay of

Visualization and correction of automated segmentation, tracking and lineaging from 5-D stem cell image sequences.

PubMed

Wait, Eric; Winter, Mark; Bjornsson, Chris; Kokovay, Erzsebet; Wang, Yue; Goderie, Susan; Temple, Sally; Cohen, Andrew R

2014-10-03

Neural stem cells are motile and proliferative cells that undergo mitosis, dividing to produce daughter cells and ultimately generating differentiated neurons and glia. Understanding the mechanisms controlling neural stem cell proliferation and differentiation will play a key role in the emerging fields of regenerative medicine and cancer therapeutics. Stem cell studies in vitro from 2-D image data are well established. Visualizing and analyzing large three dimensional images of intact tissue is a challenging task. It becomes more difficult as the dimensionality of the image data increases to include time and additional fluorescence channels. There is a pressing need for 5-D image analysis and visualization tools to study cellular dynamics in the intact niche and to quantify the role that environmental factors play in determining cell fate. We present an application that integrates visualization and quantitative analysis of 5-D (x,y,z,t,channel) and large montage confocal fluorescence microscopy images. The image sequences show stem cells together with blood vessels, enabling quantification of the dynamic behaviors of stem cells in relation to their vascular niche, with applications in developmental and cancer biology. Our application automatically segments, tracks, and lineages the image sequence data and then allows the user to view and edit the results of automated algorithms in a stereoscopic 3-D window while simultaneously viewing the stem cell lineage tree in a 2-D window. Using the GPU to store and render the image sequence data enables a hybrid computational approach. An inference-based approach utilizing user-provided edits to automatically correct related mistakes executes interactively on the system CPU while the GPU handles 3-D visualization tasks. By exploiting commodity computer gaming hardware, we have developed an application that can be run in the laboratory to facilitate rapid iteration through biological experiments. We combine unsupervised image

Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network.

PubMed

Saxena, Pratik; Bojar, Daniel; Zulewski, Henryk; Fussenegger, Martin

2017-10-10

We previously reported novel technology to differentiate induced pluripotent stem cells (IPSCs) into glucose-sensitive insulin-secreting beta-like cells by engineering a synthetic lineage-control network regulated by the licensed food additive vanillic acid. This genetic network was able to program intricate expression dynamics of the key transcription factors Ngn3 (neurogenin 3, OFF-ON-OFF), Pdx1 (pancreatic and duodenal homeobox 1, ON-OFF-ON) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A, OFF-ON) to guide the differentiation of IPSC-derived pancreatic progenitor cells to beta-like cells. In the present study, we show for the first time that this network can also program the expression dynamics of Ngn3, Pdx1 and MafA in human embryonic stem cell (hESC)-derived pancreatic progenitor cells and drive differentiation of these cells into glucose-sensitive insulin-secreting beta-like cells. Therefore, synthetic lineage-control networks appear to be a robust methodology for differentiating pluripotent stem cells into somatic cell types for basic research and regenerative medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Estimating the diversity of dinosaurs

NASA Astrophysics Data System (ADS)

Wang, Steve C.; Dodson, Peter

2006-09-01

Despite current interest in estimating the diversity of fossil and extant groups, little effort has been devoted to estimating the diversity of dinosaurs. Here we estimate the diversity of nonavian dinosaurs at ≈1,850 genera, including those that remain to be discovered. With 527 genera currently described, at least 71% of dinosaur genera thus remain unknown. Although known diversity declined in the last stage of the Cretaceous, estimated diversity was steady, suggesting that dinosaurs as a whole were not in decline in the 10 million years before their ultimate extinction. We also show that known diversity is biased by the availability of fossiliferous rock outcrop. Finally, by using a logistic model, we predict that 75% of discoverable genera will be known within 60-100 years and 90% within 100-140 years. Because of nonrandom factors affecting the process of fossil discovery (which preclude the possibility of computing realistic confidence bounds), our estimate of diversity is likely to be a lower bound.

The Development of a Virtual Dinosaur Museum

ERIC Educational Resources Information Center

Tarng, Wernhuar; Liou, Hsin-Hun

2007-01-01

The objective of this article is to study the network and virtual reality technologies for developing a virtual dinosaur museum, which provides a Web-learning environment for students of all ages and the general public to know more about dinosaurs. We first investigate the method for building the 3D dynamic models of dinosaurs, and then describe…

Differentiation of Mesenchymal Stem Cells Towards Nephrogenic Lineage and Their Enhanced Resistance to Oxygen Peroxide-induced Oxidative Stress.

PubMed

Tayyeb, Asima; Shahzad, Naveed; Ali, Gibran

2017-07-01

Mesenchymal stem cells (MSCs) have been publicized to ameliorate kidney injury both in vitro and in vivo. However, very less is known if MSCs can be differentiated towards renal lineages and their further application potential in kidney injuries. The present study developed a conditioning system of growth factors fibroblast growth factor 2, transforming growth factor-β2, and leukemia inhibitory factor for in vitro differentiation of MSCs isolated from different sources towards nephrogenic lineage. Less invasively isolated adipose-derived MSCs were also compared to bone marrow-derived MSCs for their differentiation potential to induce renal cell. Differentiated MSCs were further evaluated for their resistance to oxidative stress induced by oxygen peroxide. A combination of growth factors successfully induced differentiation of MSCs. Both types of differentiated cells showed significant expression of pronephrogenic markers (Wnt4, Wt1, and Pax2) and renal epithelial markers (Ecad and ZO1). In contrast, expression of mesenchymal stem cells marker Oct4 and Vim were downregulated. Furthermore, differentiated adipose-derived MSCs and bone marrow-derived MSCs showed enhanced and comparable resistance to oxygen peroxide-induced oxidative stress. Adipose-derived MSC provides a promising alternative to bone marrow-derived MSC as a source of autologous stem cells in human kidney injuries. In addition, differentiated MSCs with further in vivo investigations may serve as a cell source for tissue engineering or cell therapy in different renal ailments.

Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

PubMed

Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

2017-09-01

Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The evolution of dinosaurs.

PubMed

Sereno, P C

1999-06-25

The ascendancy of dinosaurs on land near the close of the Triassic now appears to have been as accidental and opportunistic as their demise and replacement by therian mammals at the end of the Cretaceous. The dinosaurian radiation, launched by 1-meter-long bipeds, was slower in tempo and more restricted in adaptive scope than that of therian mammals. A notable exception was the evolution of birds from small-bodied predatory dinosaurs, which involved a dramatic decrease in body size. Recurring phylogenetic trends among dinosaurs include, to the contrary, increase in body size. There is no evidence for co-evolution between predators and prey or between herbivores and flowering plants. As the major land masses drifted apart, dinosaurian biogeography was molded more by regional extinction and intercontinental dispersal than by the breakup sequence of Pangaea.

A New Saurolophine Dinosaur from the Latest Cretaceous of Far Eastern Russia

PubMed Central

Godefroit, Pascal; Bolotsky, Yuri L.; Lauters, Pascaline

2012-01-01

Background Four main dinosaur sites have been investigated in latest Cretaceous deposits from the Amur/Heilongjiang Region: Jiayin and Wulaga in China (Yuliangze Formation), Blagoveschensk and Kundur in Russia (Udurchukan Formation). More than 90% of the bones discovered in these localities belong to hollow-crested lambeosaurine saurolophids, but flat-headed saurolophines are also represented: Kerberosaurus manakini at Blagoveschensk and Wulagasaurus dongi at Wulaga. Methodology/Principal Findings Herein we describe a new saurolophine dinosaur, Kundurosaurus nagornyi gen. et sp. nov., from the Udurchukan Formation (Maastrichtian) of Kundur, represented by disarticulated cranial and postcranial material. This new taxon is diagnosed by four autapomorphies. Conclusions/Significance A phylogenetic analysis of saurolophines indicates that Kundurosaurus nagornyi is nested within a rather robust clade including Edmontosaurus spp., Saurolophus spp., and Prosaurolophus maximus, possibly as a sister-taxon for Kerberosaurus manakini also from the Udurchukan Formation of Far Eastern Russia. The high diversity and mosaic distribution of Maastrichtian hadrosaurid faunas in the Amur-Heilongjiang region are the result of a complex palaeogeographical history and imply that many independent hadrosaurid lineages dispersed without any problem between western America and eastern Asia at the end of the Cretaceous. PMID:22666331

Bone histology indicates insular dwarfism in a new Late Jurassic sauropod dinosaur.

PubMed

Sander, P Martin; Mateus, Octávio; Laven, Thomas; Knötschke, Nils

2006-06-08

Sauropod dinosaurs were the largest animals ever to inhabit the land, with truly gigantic forms in at least three lineages. Small species with an adult body mass less than five tonnes are very rare, and small sauropod bones generally represent juveniles. Here we describe a new diminutive species of basal macronarian sauropod, Europasaurus holgeri gen. et sp. nov., and on the basis of bone histology we show it to have been a dwarf species. The fossils, including excellent skull material, come from Kimmeridgian marine beds of northern Germany, and record more than 11 individuals of sauropods 1.7 to 6.2 m in total body length. Morphological overlap between partial skeletons and isolated bones links all material to the same new taxon. Cortical histology of femora and tibiae indicates that size differences within the specimens are due to different ontogenetic stages, from juveniles to fully grown individuals. The little dinosaurs must have lived on one of the large islands around the Lower Saxony basin. Comparison with the long-bone histology of large-bodied sauropods suggests that the island dwarf species evolved through a decrease in growth rate from its larger ancestor.

Dinosaur incubation periods directly determined from growth-line counts in embryonic teeth show reptilian-grade development.

PubMed

Erickson, Gregory M; Zelenitsky, Darla K; Kay, David Ian; Norell, Mark A

2017-01-17

Birds stand out from other egg-laying amniotes by producing relatively small numbers of large eggs with very short incubation periods (average 11-85 d). This aspect promotes high survivorship by limiting exposure to predation and environmental perturbation, allows for larger more fit young, and facilitates rapid attainment of adult size. Birds are living dinosaurs; their rapid development has been considered to reflect the primitive dinosaurian condition. Here, nonavian dinosaurian incubation periods in both small and large ornithischian taxa are empirically determined through growth-line counts in embryonic teeth. Our results show unexpectedly slow incubation (2.8 and 5.8 mo) like those of outgroup reptiles. Developmental and physiological constraints would have rendered tooth formation and incubation inherently slow in other dinosaur lineages and basal birds. The capacity to determine incubation periods in extinct egg-laying amniotes has implications for dinosaurian embryology, life history strategies, and survivorship across the Cretaceous-Paleogene mass extinction event.

Dinosaur incubation periods directly determined from growth-line counts in embryonic teeth show reptilian-grade development

PubMed Central

Erickson, Gregory M.; Zelenitsky, Darla K.; Kay, David Ian; Norell, Mark A.

2017-01-01

Birds stand out from other egg-laying amniotes by producing relatively small numbers of large eggs with very short incubation periods (average 11–85 d). This aspect promotes high survivorship by limiting exposure to predation and environmental perturbation, allows for larger more fit young, and facilitates rapid attainment of adult size. Birds are living dinosaurs; their rapid development has been considered to reflect the primitive dinosaurian condition. Here, nonavian dinosaurian incubation periods in both small and large ornithischian taxa are empirically determined through growth-line counts in embryonic teeth. Our results show unexpectedly slow incubation (2.8 and 5.8 mo) like those of outgroup reptiles. Developmental and physiological constraints would have rendered tooth formation and incubation inherently slow in other dinosaur lineages and basal birds. The capacity to determine incubation periods in extinct egg-laying amniotes has implications for dinosaurian embryology, life history strategies, and survivorship across the Cretaceous–Paleogene mass extinction event. PMID:28049837

Comment on "Evidence for mesothermy in dinosaurs".

PubMed

Myhrvold, Nathan P

2015-05-29

Grady et al. (Reports, 13 June 2014, p. 1268) studied dinosaur metabolism by comparison of maximum somatic growth rate allometry with groups of known metabolism. They concluded that dinosaurs exhibited mesothermy, a metabolic rate intermediate between endothermy and ectothermy. Multiple statistical and methodological issues call into question the evidence for dinosaur mesothermy. Copyright © 2015, American Association for the Advancement of Science.

Dinosaur morphological diversity and the end-Cretaceous extinction.

PubMed

Brusatte, Stephen L; Butler, Richard J; Prieto-Márquez, Albert; Norell, Mark A

2012-05-01

The extinction of non-avian dinosaurs 65 million years ago is a perpetual topic of fascination, and lasting debate has focused on whether dinosaur biodiversity was in decline before end-Cretaceous volcanism and bolide impact. Here we calculate the morphological disparity (anatomical variability) exhibited by seven major dinosaur subgroups during the latest Cretaceous, at both global and regional scales. Our results demonstrate both geographic and clade-specific heterogeneity. Large-bodied bulk-feeding herbivores (ceratopsids and hadrosauroids) and some North American taxa declined in disparity during the final two stages of the Cretaceous, whereas carnivorous dinosaurs, mid-sized herbivores, and some Asian taxa did not. Late Cretaceous dinosaur evolution, therefore, was complex: there was no universal biodiversity trend and the intensively studied North American record may reveal primarily local patterns. At least some dinosaur groups, however, did endure long-term declines in morphological variability before their extinction.

If You Were a Dinosaur...

ERIC Educational Resources Information Center

Ashbrook, Peggy

2010-01-01

Dinosaurs are one of those science topics that draw children in and teach them about concepts like measuring and using descriptive language. Learning about dinosaurs, although not hands-on like observing and recording caterpillar growth, develops critical thinking and introduces animal diversity and the relations between body form and function.…

Dinosaur extinction: closing the '3 m gap'.

PubMed

Lyson, Tyler R; Bercovici, Antoine; Chester, Stephen G B; Sargis, Eric J; Pearson, Dean; Joyce, Walter G

2011-12-23

Modern debate regarding the extinction of non-avian dinosaurs was ignited by the publication of the Cretaceous-Tertiary (K-T) asteroid impact theory and has seen 30 years of dispute over the position of the stratigraphically youngest in situ dinosaur. A zone devoid of dinosaur fossils reported from the last 3 m of the Upper Cretaceous, coined the '3 m gap', has helped drive controversy. Here, we report the discovery of the stratigraphically youngest in situ dinosaur specimen: a ceratopsian brow horn found in a poorly rooted, silty, mudstone floodplain deposit located no more than 13 cm below the palynologically defined boundary. The K-T boundary is identified using three criteria: (i) decrease in Cretaceous palynomorphs without subsequent recovery, (ii) the existence of a 'fern spike', and (iii) correlation to a nearby stratigraphic section where primary extraterrestrial impact markers are present (e.g. iridium anomaly, spherules, shocked quartz). The in situ specimen demonstrates that a gap devoid of non-avian dinosaur fossils does not exist and is inconsistent with the hypothesis that non-avian dinosaurs were extinct prior to the K-T boundary impact event.

Making Sense of Dinosaur Tracks

ERIC Educational Resources Information Center

MacKenzie, Ann Haley; McDowell, Brian

2012-01-01

What do paleontologists, dinosaur tracks, and the nature of science have in common? They're combined here in an inquiry activity where students use methods of observation and inference to devise evidence-based explanations for the data they collect about dinosaur tracks, much like the methods used by paleontologists. Students then debate the…

Do feathered dinosaurs exist? Testing the hypothesis on neontological and paleontological evidence.

PubMed

Feduccia, Alan; Lingham-Soliar, Theagarten; Hinchliffe, J Richard

2005-11-01

Spain. In the second part of the study we examine evidence relating to the most critical character thought to link birds to derived theropods, a tridactyl hand composed of digits 1-2-3. We maintain the evidence supports interpretation of bird wing digit identity as 2,3,4, which appears different from that in theropod dinosaurs. The phylogenetic significance of Chinese microraptors is also discussed, with respect to bird origins and flight origins. We suggest that a possible solution to the disparate data is that Aves plus bird-like maniraptoran theropods (e.g., microraptors and others) may be a separate clade, distinctive from the main lineage of Theropoda, a remnant of the early avian radiation, exhibiting all stages of flight and flightlessness. J. Morphol. (c) Wiley-Liss, Inc.

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

PubMed

Casey, Alison E; Sinha, Ankit; Singhania, Rajat; Livingstone, Julie; Waterhouse, Paul; Tharmapalan, Pirashaanthy; Cruickshank, Jennifer; Shehata, Mona; Drysdale, Erik; Fang, Hui; Kim, Hyeyeon; Isserlin, Ruth; Bailey, Swneke; Medina, Tiago; Deblois, Genevieve; Shiah, Yu-Jia; Barsyte-Lovejoy, Dalia; Hofer, Stefan; Bader, Gary; Lupien, Mathieu; Arrowsmith, Cheryl; Knapp, Stefan; De Carvalho, Daniel; Berman, Hal; Boutros, Paul C; Kislinger, Thomas; Khokha, Rama

2018-06-19

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology. © 2018 Casey et al.

Early crocodylomorph increases top tier predator diversity during rise of dinosaurs.

PubMed

Zanno, Lindsay E; Drymala, Susan; Nesbitt, Sterling J; Schneider, Vincent P

2015-03-19

Triassic predatory guild evolution reflects a period of ecological flux spurred by the catastrophic end-Permian mass extinction and terminating with the global ecological dominance of dinosaurs in the early Jurassic. In responding to this dynamic ecospace, terrestrial predator diversity attained new levels, prompting unique trophic webs with a seeming overabundance of carnivorous taxa and the evolution of entirely new predatory clades. Key among these was Crocodylomorpha, the largest living reptiles and only one of two archosaurian lineages that survive to the present day. In contrast to their existing role as top, semi-aquatic predators, the earliest crocodylomorphs were generally small-bodied, terrestrial faunivores, occupying subsidiary (meso) predator roles. Here we describe Carnufex carolinensis a new, unexpectedly large-bodied taxon with a slender and ornamented skull from the Carnian Pekin Formation (~231 Ma), representing one of the oldest and earliest diverging crocodylomorphs described to date. Carnufex bridges a problematic gap in the early evolution of pseudosuchians by spanning key transitions in bauplan evolution and body mass near the origin of Crocodylomorpha. With a skull length of >50 cm, the new taxon documents a rare instance of crocodylomorphs ascending to top-tier predator guilds in the equatorial regions of Pangea prior to the dominance of dinosaurs.

Early crocodylomorph increases top tier predator diversity during rise of dinosaurs

PubMed Central

Zanno, Lindsay E.; Drymala, Susan; Nesbitt, Sterling J.; Schneider, Vincent P.

2015-01-01

Triassic predatory guild evolution reflects a period of ecological flux spurred by the catastrophic end-Permian mass extinction and terminating with the global ecological dominance of dinosaurs in the early Jurassic. In responding to this dynamic ecospace, terrestrial predator diversity attained new levels, prompting unique trophic webs with a seeming overabundance of carnivorous taxa and the evolution of entirely new predatory clades. Key among these was Crocodylomorpha, the largest living reptiles and only one of two archosaurian lineages that survive to the present day. In contrast to their existing role as top, semi-aquatic predators, the earliest crocodylomorphs were generally small-bodied, terrestrial faunivores, occupying subsidiary (meso) predator roles. Here we describe Carnufex carolinensis a new, unexpectedly large-bodied taxon with a slender and ornamented skull from the Carnian Pekin Formation (~231 Ma), representing one of the oldest and earliest diverging crocodylomorphs described to date. Carnufex bridges a problematic gap in the early evolution of pseudosuchians by spanning key transitions in bauplan evolution and body mass near the origin of Crocodylomorpha. With a skull length of >50 cm, the new taxon documents a rare instance of crocodylomorphs ascending to top-tier predator guilds in the equatorial regions of Pangea prior to the dominance of dinosaurs. PMID:25787306

A new giant titanosaur sheds light on body mass evolution among sauropod dinosaurs.

PubMed

Carballido, José L; Pol, Diego; Otero, Alejandro; Cerda, Ignacio A; Salgado, Leonardo; Garrido, Alberto C; Ramezani, Jahandar; Cúneo, Néstor R; Krause, Javier M

2017-08-16

Titanosauria was the most diverse and successful lineage of sauropod dinosaurs. This clade had its major radiation during the middle Early Cretaceous and survived up to the end of that period. Among sauropods, this lineage has the most disparate values of body mass, including the smallest and largest sauropods known. Although recent findings have improved our knowledge on giant titanosaur anatomy, there are still many unknown aspects about their evolution, especially for the most gigantic forms and the evolution of body mass in this clade. Here we describe a new giant titanosaur, which represents the largest species described so far and one of the most complete titanosaurs. Its inclusion in an extended phylogenetic analysis and the optimization of body mass reveals the presence of an endemic clade of giant titanosaurs inhabited Patagonia between the Albian and the Santonian. This clade includes most of the giant species of titanosaurs and represents the major increase in body mass in the history of Titanosauria. © 2017 The Author(s).

Synchrotron scanning reveals amphibious ecomorphology in a new clade of bird-like dinosaurs.

PubMed

Cau, Andrea; Beyrand, Vincent; Voeten, Dennis F A E; Fernandez, Vincent; Tafforeau, Paul; Stein, Koen; Barsbold, Rinchen; Tsogtbaatar, Khishigjav; Currie, Philip J; Godefroit, Pascal

2017-12-21

Maniraptora includes birds and their closest relatives among theropod dinosaurs. During the Cretaceous period, several maniraptoran lineages diverged from the ancestral coelurosaurian bauplan and evolved novel ecomorphologies, including active flight, gigantism, cursoriality and herbivory. Propagation X-ray phase-contrast synchrotron microtomography of a well-preserved maniraptoran from Mongolia, still partially embedded in the rock matrix, revealed a mosaic of features, most of them absent among non-avian maniraptorans but shared by reptilian and avian groups with aquatic or semiaquatic ecologies. This new theropod, Halszkaraptor escuilliei gen. et sp. nov., is related to other enigmatic Late Cretaceous maniraptorans from Mongolia in a novel clade at the root of Dromaeosauridae. This lineage adds an amphibious ecomorphology to those evolved by maniraptorans: it acquired a predatory mode that relied mainly on neck hyperelongation for food procurement, it coupled the obligatory bipedalism of theropods with forelimb proportions that may support a swimming function, and it developed postural adaptations convergent with short-tailed birds.

Synchrotron scanning reveals amphibious ecomorphology in a new clade of bird-like dinosaurs

NASA Astrophysics Data System (ADS)

Cau, Andrea; Beyrand, Vincent; Voeten, Dennis F. A. E.; Fernandez, Vincent; Tafforeau, Paul; Stein, Koen; Barsbold, Rinchen; Tsogtbaatar, Khishigjav; Currie, Philip J.; Godefroit, Pascal

2017-12-01

Maniraptora includes birds and their closest relatives among theropod dinosaurs. During the Cretaceous period, several maniraptoran lineages diverged from the ancestral coelurosaurian bauplan and evolved novel ecomorphologies, including active flight, gigantism, cursoriality and herbivory. Propagation X-ray phase-contrast synchrotron microtomography of a well-preserved maniraptoran from Mongolia, still partially embedded in the rock matrix, revealed a mosaic of features, most of them absent among non-avian maniraptorans but shared by reptilian and avian groups with aquatic or semiaquatic ecologies. This new theropod, Halszkaraptor escuilliei gen. et sp. nov., is related to other enigmatic Late Cretaceous maniraptorans from Mongolia in a novel clade at the root of Dromaeosauridae. This lineage adds an amphibious ecomorphology to those evolved by maniraptorans: it acquired a predatory mode that relied mainly on neck hyperelongation for food procurement, it coupled the obligatory bipedalism of theropods with forelimb proportions that may support a swimming function, and it developed postural adaptations convergent with short-tailed birds.

New insights into dinosaur jaw muscle anatomy.

PubMed

Holliday, Casey M

2009-09-01

Jaw muscles are key components of the head and critical to testing hypotheses of soft-tissue homology, skull function, and evolution. Dinosaurs evolved an extraordinary diversity of cranial forms adapted to a variety of feeding behaviors. However, disparate evolutionary transformations in head shape and function among dinosaurs and their living relatives, birds and crocodylians, impair straightforward reconstructions of muscles, and other important cephalic soft tissues. This study presents the osteological correlates and inferred soft tissue anatomy of the jaw muscles and relevant neurovasculature in the temporal region of the dinosaur head. Hypotheses of jaw muscle homology were tested across a broad range archosaur and sauropsid taxa to more accurately infer muscle attachments in the adductor chambers of non-avian dinosaurs. Many dinosaurs likely possessed m. levator pterygoideus, a trait shared with lepidosaurs but not extant archosaurs. Several major clades of dinosaurs (e.g., Ornithopoda, Ceratopsidae, Sauropoda) eliminated the epipterygoid, thus impacting interpretations of m. pseudotemporalis profundus. M. pseudotemporalis superficialis most likely attached to the caudoventral surface of the laterosphenoid, a trait shared with extant archosaurs. Although mm. adductor mandibulae externus profundus and medialis likely attached to the caudal half of the dorsotemporal fossa and coronoid process, clear osteological correlates separating the individual bellies are rare. Most dinosaur clades possess osteological correlates indicative of a pterygoideus ventralis muscle that attaches to the lateral surface of the mandible, although the muscle may have extended as far as the jugal in some taxa (e.g., hadrosaurs, tyrannosaurs). The cranial and mandibular attachments of mm adductor mandibulae externus superficialis and adductor mandibulae posterior were consistent across all taxa studied. These new data greatly increase the interpretive resolution of head anatomy in

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model

PubMed Central

Cabezas-Wallscheid, Nina; Eichwald, Victoria; de Graaf, Jos; Löwer, Martin; Lehr, Hans-Anton; Kreft, Andreas; Eshkind, Leonid; Hildebrandt, Andreas; Abassi, Yasmin; Heck, Rosario; Dehof, Anna Katharina; Ohngemach, Svetlana; Sprengel, Rolf; Wörtge, Simone; Schmitt, Steffen; Lotz, Johannes; Meyer, Claudius; Kindler, Thomas; Zhang, Dong-Er; Kaina, Bernd; Castle, John C; Trumpp, Andreas; Sahin, Ugur; Bockamp, Ernesto

2013-01-01

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. PMID:24124051

Nitric oxide balances osteoblast and adipocyte lineage differentiation via the JNK/MAPK signaling pathway in periodontal ligament stem cells.

PubMed

Yang, Shan; Guo, Lijia; Su, Yingying; Wen, Jing; Du, Juan; Li, Xiaoyan; Liu, Yitong; Feng, Jie; Xie, Yongmei; Bai, Yuxing; Wang, Hao; Liu, Yi

2018-05-02

Critical tissues that undergo regeneration in periodontal tissue are of mesenchymal origin; thus, investigating the regulatory mechanisms underlying the fate of periodontal ligament stem cells could be beneficial for application in periodontal tissue regeneration. Nitric oxide (NO) regulates many biological processes in developing embryos and adult stem cells. The present study was designed to investigate the effects of NO on the function of human periodontal ligament stem cells (PDLSCs) as well as to elucidate the underlying molecular mechanisms. Immunofluorescent staining and flow cytometry were used for stem cell identification. Western blot, reverse transcription polymerase chain reaction (RT-PCR), immunofluorescent staining, and flow cytometry were used to examine the expression of NO-synthesizing enzymes. The proliferative capacity of PDLSCs was determined by EdU assays. The osteogenic potential of PDLSCs was tested using alkaline phosphatase (ALP) staining, Alizarin Red staining, and calcium concentration detection. Oil Red O staining was used to analyze the adipogenic ability. Western blot, RT-PCR, and staining were used to examine the signaling pathway. Human PDLSCs expressed both inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) and produced NO. Blocking the generation of NO with the NOS inhibitor L-N G -monomethyl arginine (L-NMMA) had no influence on PDLSC proliferation and apoptosis but significantly attenuated the osteogenic differentiation capacity and stimulated the adipogenic differentiation capacity of PDLSCs. Increasing the physiological level of NO with NO donor sodium nitroprusside (SNP) significantly promoted the osteogenic differentiation capacity but reduced the adipogenic differentiation capacity of PDLSCs. NO balances the osteoblast and adipocyte lineage differentiation in periodontal ligament stem cells via the c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling pathway. NO is essential for

All about Dinosaurs. Animal Life for Children. [Videotape].

ERIC Educational Resources Information Center

2000

Dinosaurs were the rulers of the land 65 million years ago. In this videotape, children learn more about the different kinds of dinosaurs by viewing vivid illustrations and fossil discoveries. Students compare the dinosaurs to their modern kin--snakes, lizards, and crocodiles. Students also listen to different theories to try to answer the big…

The Great Dinosaur Feud: Science against All Odds

ERIC Educational Resources Information Center

Clary, Renee; Wandersee, James; Carpinelli, Amy

2008-01-01

In the 19th century, the race to uncover dinosaur fossils and name new dinosaur species inspired two rival scientists, Edward Drinker Cope and Othniel Charles Marsh, to behave in ways that were the antithesis of scientific methods. Subterfuge, theft, and espionage were the ingredients of the Great Dinosaur Feud. Because students often enjoy…

Air-filled postcranial bones in theropod dinosaurs: physiological implications and the 'reptile'-bird transition.

PubMed

Benson, Roger B J; Butler, Richard J; Carrano, Matthew T; O'Connor, Patrick M

2012-02-01

Pneumatic (air-filled) postcranial bones are unique to birds among extant tetrapods. Unambiguous skeletal correlates of postcranial pneumaticity first appeared in the Late Triassic (approximately 210 million years ago), when they evolved independently in several groups of bird-line archosaurs (ornithodirans). These include the theropod dinosaurs (of which birds are extant representatives), the pterosaurs, and sauropodomorph dinosaurs. Postulated functions of skeletal pneumatisation include weight reduction in large-bodied or flying taxa, and density reduction resulting in energetic savings during foraging and locomotion. However, the influence of these hypotheses on the early evolution of pneumaticity has not been studied in detail previously. We review recent work on the significance of pneumaticity for understanding the biology of extinct ornithodirans, and present detailed new data on the proportion of the skeleton that was pneumatised in 131 non-avian theropods and Archaeopteryx. This includes all taxa known from significant postcranial remains. Pneumaticity of the cervical and anterior dorsal vertebrae occurred early in theropod evolution. This 'common pattern' was conserved on the line leading to birds, and is likely present in Archaeopteryx. Increases in skeletal pneumaticity occurred independently in as many as 12 lineages, highlighting a remarkably high number of parallel acquisitions of a bird-like feature among non-avian theropods. Using a quantitative comparative framework, we show that evolutionary increases in skeletal pneumaticity are significantly concentrated in lineages with large body size, suggesting that mass reduction in response to gravitational constraints at large body sizes influenced the early evolution of pneumaticity. However, the body size threshold for extensive pneumatisation is lower in theropod lineages more closely related to birds (maniraptorans). Thus, relaxation of the relationship between body size and pneumatisation preceded

Stem cell plasticity.

PubMed

Lakshmipathy, Uma; Verfaillie, Catherine

2005-01-01

The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

Gene family innovation, conservation and loss on the animal stem lineage.

PubMed

Richter, Daniel J; Fozouni, Parinaz; Eisen, Michael; King, Nicole

2018-05-31

Choanoflagellates, the closest living relatives of animals, can provide unique insights into the changes in gene content that preceded the origin of animals. However, only two choanoflagellate genomes are currently available, providing poor coverage of their diversity. We sequenced transcriptomes of 19 additional choanoflagellate species to produce a comprehensive reconstruction of the gains and losses that shaped the ancestral animal gene repertoire. We identified ~1,944 gene families that originated on the animal stem lineage, of which only 39 are conserved across all animals in our study. In addition, ~372 gene families previously thought to be animal-specific, including Notch, Delta, and homologs of the animal Toll-like receptor genes, instead evolved prior to the animal-choanoflagellate divergence. Our findings contribute to an increasingly detailed portrait of the gene families that defined the biology of the Urmetazoan and that may underpin core features of extant animals. © 2018, Richter et al.

A Dual Role for SOX10 in the Maintenance of the Postnatal Melanocyte Lineage and the Differentiation of Melanocyte Stem Cell Progenitors

PubMed Central

Harris, Melissa L.; Buac, Kristina; Shakhova, Olga; Hakami, Ramin M.; Wegner, Michael; Sommer, Lukas; Pavan, William J.

2013-01-01

During embryogenesis, the transcription factor, Sox10, drives the survival and differentiation of the melanocyte lineage. However, the role that Sox10 plays in postnatal melanocytes is not established. We show in vivo that melanocyte stem cells (McSCs) and more differentiated melanocytes express SOX10 but that McSCs remain undifferentiated. Sox10 knockout (Sox10fl; Tg(Tyr::CreER)) results in loss of both McSCs and differentiated melanocytes, while overexpression of Sox10 (Tg(DctSox10)) causes premature differentiation and loss of McSCs, leading to hair graying. This suggests that levels of SOX10 are key to normal McSC function and Sox10 must be downregulated for McSC establishment and maintenance. We examined whether the mechanism of Tg(DctSox10) hair graying is through increased expression of Mitf, a target of SOX10, by asking if haploinsufficiency for Mitf (Mitfvga9) can rescue hair graying in Tg(DctSox10) animals. Surprisingly, Mitfvga9 does not mitigate but exacerbates Tg(DctSox10) hair graying suggesting that MITF participates in the negative regulation of Sox10 in McSCs. These observations demonstrate that while SOX10 is necessary to maintain the postnatal melanocyte lineage it is simultaneously prevented from driving differentiation in the McSCs. This data illustrates how tissue-specific stem cells can arise from lineage-specified precursors through the regulation of the very transcription factors important in defining that lineage. PMID:23935512

"Teachosaurus" and "Learnoceratops": Dinosaurs as a Motivating Cross-Curricular Theme

ERIC Educational Resources Information Center

Duggan, Denis

2011-01-01

The author takes a look into the benefits that dinosaurs may bring to the classroom. He discusses how he used dinosaurs as a cross-curricular theme to improve children's understanding and knowledge of science concepts. To investigate what a child might learn from dinosaurs, he started by comparing the many non-fiction dinosaur books using the…

Stem Cell Differentiation Toward the Myogenic Lineage for Muscle Tissue Regeneration: A Focus on Muscular Dystrophy.

PubMed

Ostrovidov, Serge; Shi, Xuetao; Sadeghian, Ramin Banan; Salehi, Sahar; Fujie, Toshinori; Bae, Hojae; Ramalingam, Murugan; Khademhosseini, Ali

2015-12-01

Skeletal muscle tissue engineering is one of the important ways for regenerating functionally defective muscles. Among the myopathies, the Duchenne muscular dystrophy (DMD) is a progressive disease due to mutations of the dystrophin gene leading to progressive myofiber degeneration with severe symptoms. Although current therapies in muscular dystrophy are still very challenging, important progress has been made in materials science and in cellular technologies with the use of stem cells. It is therefore useful to review these advances and the results obtained in a clinical point of view. This article focuses on the differentiation of stem cells into myoblasts, and their application in muscular dystrophy. After an overview of the different stem cells that can be induced to differentiate into the myogenic lineage, we introduce scaffolding materials used for muscular tissue engineering. We then described some widely used methods to differentiate different types of stem cell into myoblasts. We highlight recent insights obtained in therapies for muscular dystrophy. Finally, we conclude with a discussion on stem cell technology. We discussed in parallel the benefits brought by the evolution of the materials and by the expansion of cell sources which can differentiate into myoblasts. We also discussed on future challenges for clinical applications and how to accelerate the translation from the research to the clinic in the frame of DMD.

Life cycle and morphology of a cambrian stem-lineage loriciferan.

PubMed

Peel, John S; Stein, Martin; Kristensen, Reinhardt Møbjerg

2013-01-01

Cycloneuralians form a rich and diverse element within Cambrian assemblages of exceptionally preserved fossils. Most resemble priapulid worms whereas other Cycloneuralia (Nematoda, Nematomorpha, Kinorhyncha, Loricifera), well known at the present day, have little or no fossil record. First reports of Sirilorica Peel, 2010 from the lower Cambrian Sirius Passet fauna of North Greenland described a tubular lorica covering the abdomen and part of a well developed introvert with a circlet of 6 grasping denticles near the lorica. The introvert is now known to terminate in a narrow mouth tube, while a conical anal field is also developed. Broad muscular bands between the plates in the lorica indicate that it was capable of movement by rhythmic expansion and contraction of the lorica. Sirilorica is regarded as a macrobenthic member of the stem-lineage of the miniaturised, interstitial, present day Loricifera. Like loriciferans, Sirilorica is now known to have grown by moulting. Evidence of the life cycle of Sirilorica is described, including a large post-larval stage and probably an initial larva similar to that of the middle Cambrian fossil Orstenoloricusshergoldii.

Life Cycle and Morphology of a Cambrian Stem-Lineage Loriciferan

PubMed Central

Peel, John S.; Stein, Martin; Kristensen, Reinhardt Møbjerg

2013-01-01

Cycloneuralians form a rich and diverse element within Cambrian assemblages of exceptionally preserved fossils. Most resemble priapulid worms whereas other Cycloneuralia (Nematoda, Nematomorpha, Kinorhyncha, Loricifera), well known at the present day, have little or no fossil record. First reports of Sirilorica Peel, 2010 from the lower Cambrian Sirius Passet fauna of North Greenland described a tubular lorica covering the abdomen and part of a well developed introvert with a circlet of 6 grasping denticles near the lorica. The introvert is now known to terminate in a narrow mouth tube, while a conical anal field is also developed. Broad muscular bands between the plates in the lorica indicate that it was capable of movement by rhythmic expansion and contraction of the lorica. Sirilorica is regarded as a macrobenthic member of the stem-lineage of the miniaturised, interstitial, present day Loricifera. Like loriciferans, Sirilorica is now known to have grown by moulting. Evidence of the life cycle of Sirilorica is described, including a large post-larval stage and probably an initial larva similar to that of the middle Cambrian fossil Orstenoloricusshergoldii . PMID:23991198

Dinosaur Fossil, Leonardo, at Ellington Field

NASA Image and Video Library

2008-03-14

Documentation of NASA's partnership with the Houston Museum of Natural Science and Montana's Great Plains Dinosaur Museum to provide an insulated facility at Ellington Field in which the Leonardo Project Team was able to X-ray Leonardo, a 77 million year old dinosaur fossil. View of the Brachylophosaurus fossil called Leonardo.

PI3 K/Akt/mTOR-mediated translational control regulates proliferation and differentiation of lineage-restricted RoSH stem cell lines

PubMed Central

Que, Jianwen; Lian, Qizhou; El Oakley, Reida M; Lim, Bing; Lim, Sai-Kiang

2007-01-01

Background We have previously derived highly similar lineage-restricted stem cell lines, RoSH and E-RoSH cell lines from mouse embryos and CD9hi SSEA-1- differentiated mouse embryonic stem cells, respectively. These cell lines are not pluripotent and differentiate readily into endothelial cells in vitro and in vivo. Results We investigated the signaling pathway that maintains proliferation of these cells in an undifferentiated state, and demonstrate that PI3 K/Akt/mTOR, but not Raf/MEK/Erk, signaling in these cells was active during proliferation and was downregulated during endothelial differentiation. Inhibition of PI3 K/Akt/mTOR signaling, but not Raf/MEK/Erk, reduced proliferation and induced expression of endothelial specific proteins. During differentiation or inhibition of PI3 K/Akt/mTOR signaling, cyclinD2 transcript abundance in ribosome-enriched RNA but not in total RNA was reduced with a corresponding reduction in protein level. In contrast, transcript abundance of endothelial-specific genes e.g. Kdr, Tek and Pdgfrα in ribosome-enriched RNA fraction was not reduced and their protein levels were increased. Together these observations suggested that translational control mediated by PI3K/Akt/mTOR signaling was critical in regulating proliferation and endothelial differentiation of lineage-restricted RoSH-like stem cell lines. Conclusion This study highlights translation regulation as a critical regulatory mechanism during proliferation and differentiation in stem cells. PMID:17892597

The oldest dinosaur? A Middle Triassic dinosauriform from Tanzania.

PubMed

Nesbitt, Sterling J; Barrett, Paul M; Werning, Sarah; Sidor, Christian A; Charig, Alan J

2013-02-23

The rise of dinosaurs was a major event in vertebrate history, but the timing of the origin and early diversification of the group remain poorly constrained. Here, we describe Nyasasaurus parringtoni gen. et sp. nov., which is identified as either the earliest known member of, or the sister-taxon to, Dinosauria. Nyasasaurus possesses a unique combination of dinosaur character states and an elevated growth rate similar to that of definitive early dinosaurs. It demonstrates that the initial dinosaur radiation occurred over a longer timescale than previously thought (possibly 15 Myr earlier), and that dinosaurs and their immediate relatives are better understood as part of a larger Middle Triassic archosauriform radiation. The African provenance of Nyasasaurus supports a southern Pangaean origin for Dinosauria.

A Unique Late Triassic Dinosauromorph Assemblage Reveals Dinosaur Ancestral Anatomy and Diet.

PubMed

Cabreira, Sergio Furtado; Kellner, Alexander Wilhelm Armin; Dias-da-Silva, Sérgio; Roberto da Silva, Lúcio; Bronzati, Mario; Marsola, Júlio Cesar de Almeida; Müller, Rodrigo Temp; Bittencourt, Jonathas de Souza; Batista, Brunna Jul'Armando; Raugust, Tiago; Carrilho, Rodrigo; Brodt, André; Langer, Max Cardoso

2016-11-21

Dinosauromorpha includes dinosaurs and other much less diverse dinosaur precursors of Triassic age, such as lagerpetids [1]. Joint occurrences of these taxa with dinosaurs are rare but more common during the latest part of that period (Norian-Rhaetian, 228-201 million years ago [mya]) [2, 3]. In contrast, the new lagerpetid and saurischian dinosaur described here were unearthed from one of the oldest rock units with dinosaur fossils worldwide, the Carnian (237-228 mya) Santa Maria Formation of south Brazil [4], a record only matched in age by much more fragmentary remains from Argentina [5]. This is the first time nearly complete dinosaur and non-dinosaur dinosauromorph remains are found together in the same excavation, clearly showing that these animals were contemporaries since the first stages of dinosaur evolution. The new lagerpetid preserves the first skull, scapular and forelimb elements, plus associated vertebrae, known for the group, revealing how dinosaurs acquired several of their typical anatomical traits. Furthermore, a novel phylogenetic analysis shows the new dinosaur as the most basal Sauropodomorpha. Its plesiomorphic teeth, strictly adapted to faunivory, provide crucial data to infer the feeding behavior of the first dinosaurs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiovascular Physiology of Dinosaurs.

PubMed

Seymour, Roger S

2016-11-01

Cardiovascular function in dinosaurs can be inferred from fossil evidence with knowledge of how metabolic rate, blood flow rate, blood pressure, and heart size are related to body size in living animals. Skeletal stature and nutrient foramen size in fossil femora provide direct evidence of a high arterial blood pressure, a large four-chambered heart, a high aerobic metabolic rate, and intense locomotion. But was the heart of a huge, long-necked sauropod dinosaur able to pump blood up 9 m to its head? ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages.

PubMed

Jiao, Fei; Wang, Juan; Dong, Zhao-Lun; Wu, Min-Juan; Zhao, Ting-Bao; Li, Dan-Dan; Wang, Xin

2012-08-01

Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them "human limb bud-derived mesenchymal stem cells" (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro.

Human Mesenchymal Stem Cells Derived From Limb Bud Can Differentiate into All Three Embryonic Germ Layers Lineages

PubMed Central

Jiao, Fei; Wang, Juan; Dong, Zhao-lun; Wu, Min-juan; Zhao, Ting-bao; Li, Dan-dan

2012-01-01

Abstract Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them “human limb bud–derived mesenchymal stem cells” (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro. PMID:22775353

Allometry in dinosaurs and mammals

NASA Astrophysics Data System (ADS)

Lee, Scott

2015-03-01

The proportions of the leg bones change as the size of an animal becomes larger since the mass of the animal increases at a faster rate than the cross-sectional area of its leg bones. For the case of elastic similarity (in which the longitudinal stress in the legs remains constant in animals of all sizes), the diameter d and length L of the femur should be related as d = A L3/2. For geometric similarity (in which all dimensions are scaled by the same factor), d = A L. For animals with femora longer than 20 cm, we find the power law relationship to be d = A Lb with b = 1.13 +/- 0.06 for extant mammals (the largest mammal being Loxodonta africana with a 1.00-m-long femur) and b = 1.18 +/- 0.02 for dinosaurs (the largest dinosaur being Brachiosaurus brancai with a 2.03-m-long femur). These data show that extinct dinosaurs and extant animals scale in the same basic manner. The large sauropods (with femora twice as long as found in elephants) scale in a manner consistent with extrapolation of the scaling shown by extant mammals. These results argue that extinct dinosaurs moved in a manner very similar to extant mammals.

Incubation times of dinosaur eggs via embryonic metabolism

NASA Astrophysics Data System (ADS)

Lee, Scott A.

2016-08-01

The incubation times for the eggs of 21 dinosaurs are determined from an estimate of their embyronic metabolic rate and the mass of the hatchlings via a mass growth model based on conservation of energy. Embryos in extant birds and crocodiles are studied in order to determine the best model for embryonic metabolism and growth. These results are used to develop a theoretical model that predicts the incubation times of an egg. This model is applied to dinosaur eggs and provides a unique window into dinosaur reproduction. The dinosaurs studied come from both Saurischia and Ornithischia. The incubation times vary from about 28 days for Archaeopteryx lithographica to about 76 days for Alamosaurus sanjuanensis.

Incubation times of dinosaur eggs via embryonic metabolism.

PubMed

Lee, Scott A

2016-08-01

The incubation times for the eggs of 21 dinosaurs are determined from an estimate of their embyronic metabolic rate and the mass of the hatchlings via a mass growth model based on conservation of energy. Embryos in extant birds and crocodiles are studied in order to determine the best model for embryonic metabolism and growth. These results are used to develop a theoretical model that predicts the incubation times of an egg. This model is applied to dinosaur eggs and provides a unique window into dinosaur reproduction. The dinosaurs studied come from both Saurischia and Ornithischia. The incubation times vary from about 28 days for Archaeopteryx lithographica to about 76 days for Alamosaurus sanjuanensis.

Mesozoic dinosaurs from Brazil and their biogeographic implications.

PubMed

Bittencourt, Jonathas S; Langer, Max C

2011-03-01

The record of dinosaur body-fossils in the Brazilian Mesozoic is restricted to the Triassic of Rio Grande do Sul and Cretaceous of various parts of the country. This includes 21 named species, two of which were regarded as nomina dubia, and 19 consensually assigned to Dinosauria. Additional eight supraspecific taxa have been identified based on fragmentary specimens and numerous dinosaur footprints known in Brazil. In fact, most Brazilian specimens related to dinosaurs are composed of isolated teeth and vertebrae. Despite the increase of fieldwork during the last decade, there are still no dinosaur body-fossils of Jurassic age and the evidence of ornithischians in Brazil is very limited. Dinosaur faunas from this country are generally correlated with those from other parts of Gondwana throughout the Mesozoic. During the Late Triassic, there is a close correspondence to Argentina and other south-Pangaea areas. Mid-Cretaceous faunas of northeastern Brazil resemble those of coeval deposits of North Africa and Argentina. Southern hemisphere spinosaurids are restricted to Africa and Brazil, whereas abelisaurids are still unknown in the Early Cretaceous of the latter. Late Cretaceous dinosaur assemblages of south-central Brazil are endemic only to genus or, more conspicuously, to species level, sharing closely related taxa with Argentina, Madagascar, Indo-Pakistan and, to a lesser degree, continental Africa.

A palaeoequatorial ornithischian and new constraints on early dinosaur diversification.

PubMed

Barrett, Paul M; Butler, Richard J; Mundil, Roland; Scheyer, Torsten M; Irmis, Randall B; Sánchez-Villagra, Marcelo R

2014-09-22

Current characterizations of early dinosaur evolution are incomplete: existing palaeobiological and phylogenetic scenarios are based on a fossil record dominated by saurischians and the implications of the early ornithischian record are often overlooked. Moreover, the timings of deep phylogenetic divergences within Dinosauria are poorly constrained owing to the absence of a rigorous chronostratigraphical framework for key Late Triassic-Early Jurassic localities. A new dinosaur from the earliest Jurassic of the Venezuelan Andes is the first basal ornithischian recovered from terrestrial deposits directly associated with a precise radioisotopic date and the first-named dinosaur from northern South America. It expands the early palaeogeographical range of Ornithischia to palaeoequatorial regions, an area sometimes thought to be devoid of early dinosaur taxa, and offers insights into early dinosaur growth rates, the evolution of sociality and the rapid tempo of the global dinosaur radiation following the end-Triassic mass extinction, helping to underscore the importance of the ornithischian record in broad-scale discussions of early dinosaur history. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Nonstimulated human uncommitted mesenchymal stem cells express cell markers of mesenchymal and neural lineages.

PubMed

Minguell, José J; Fierro, Fernando A; Epuñan, María J; Erices, Alejandro A; Sierralta, Walter D

2005-08-01

Ex vivo cultures of human bone marrow-derived mesenchymal stem cells (MSCs) contain subsets of progenitors exhibiting dissimilar properties. One of these subsets comprises uncommitted progenitors displaying distinctive features, such as morphology, a quiescent condition, growth factor production, and restricted tissue biodistribution after transplantation. In this study, we assessed the competence of these cells to express, in the absence of differentiation stimuli, markers of mesoderm and ectodermic (neural) cell lineages. Fluorescence microscopy analysis showed a unique pattern of expression of osteogenic, chondrogenic, muscle, and neural markers. The depicted "molecular signature" of these early uncommitted progenitors, in the absence of differentiation stimuli, is consistent with their multipotentiality and plasticity as suggested by several in vitro and in vivo studies.

The first 50Myr of dinosaur evolution: macroevolutionary pattern and morphological disparity.

PubMed

Brusatte, Stephen L; Benton, Michael J; Ruta, Marcello; Lloyd, Graeme T

2008-12-23

The evolutionary radiation of dinosaurs in the Late Triassic and Early Jurassic was a pivotal event in the Earth's history but is poorly understood, as previous studies have focused on vague driving mechanisms and have not untangled different macroevolutionary components (origination, diversity, abundance and disparity). We calculate the morphological disparity (morphospace occupation) of dinosaurs throughout the Late Triassic and Early Jurassic and present new measures of taxonomic diversity. Crurotarsan archosaurs, the primary dinosaur 'competitors', were significantly more disparate than dinosaurs throughout the Triassic, but underwent a devastating extinction at the Triassic-Jurassic boundary. However, dinosaur disparity showed only a slight non-significant increase after this event, arguing against the hypothesis of ecological release-driven morphospace expansion in the Early Jurassic. Instead, the main jump in dinosaur disparity occurred between the Carnian and Norian stages of the Triassic. Conversely, dinosaur diversity shows a steady increase over this time, and measures of diversification and faunal abundance indicate that the Early Jurassic was a key episode in dinosaur evolution. Thus, different aspects of the dinosaur radiation (diversity, disparity and abundance) were decoupled, and the overall macroevolutionary pattern of the first 50Myr of dinosaur evolution is more complex than often considered.

A Middle Jurassic abelisaurid from Patagonia and the early diversification of theropod dinosaurs.

PubMed

Pol, Diego; Rauhut, Oliver W M

2012-08-22

Abelisaurids are a clade of large, bizarre predatory dinosaurs, most notable for their high, short skulls and extremely reduced forelimbs. They were common in Gondwana during the Cretaceous, but exceedingly rare in the Northern Hemisphere. The oldest definitive abelisaurids so far come from the late Early Cretaceous of South America and Africa, and the early evolutionary history of the clade is still poorly known. Here, we report a new abelisaurid from the Middle Jurassic of Patagonia, Eoabelisaurus mefi gen. et sp. nov., which predates the so far oldest known secure member of this lineage by more than 40 Myr. The almost complete skeleton reveals the earliest evolutionary stages of the distinctive features of abelisaurids, such as the modification of the forelimb, which started with a reduction of the distal elements. The find underlines the explosive radiation of theropod dinosaurs in the Middle Jurassic and indicates an unexpected diversity of ceratosaurs at that time. The apparent endemism of abelisauroids to southern Gondwana during Pangean times might be due to the presence of a large, central Gondwanan desert. This indicates that, apart from continent-scale geography, aspects such as regional geography and climate are important to reconstruct the biogeographical history of Mesozoic vertebrates.

A Middle Jurassic abelisaurid from Patagonia and the early diversification of theropod dinosaurs

PubMed Central

Pol, Diego; Rauhut, Oliver W. M.

2012-01-01

Abelisaurids are a clade of large, bizarre predatory dinosaurs, most notable for their high, short skulls and extremely reduced forelimbs. They were common in Gondwana during the Cretaceous, but exceedingly rare in the Northern Hemisphere. The oldest definitive abelisaurids so far come from the late Early Cretaceous of South America and Africa, and the early evolutionary history of the clade is still poorly known. Here, we report a new abelisaurid from the Middle Jurassic of Patagonia, Eoabelisaurus mefi gen. et sp. nov., which predates the so far oldest known secure member of this lineage by more than 40 Myr. The almost complete skeleton reveals the earliest evolutionary stages of the distinctive features of abelisaurids, such as the modification of the forelimb, which started with a reduction of the distal elements. The find underlines the explosive radiation of theropod dinosaurs in the Middle Jurassic and indicates an unexpected diversity of ceratosaurs at that time. The apparent endemism of abelisauroids to southern Gondwana during Pangean times might be due to the presence of a large, central Gondwanan desert. This indicates that, apart from continent-scale geography, aspects such as regional geography and climate are important to reconstruct the biogeographical history of Mesozoic vertebrates. PMID:22628475

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

PubMed Central

Park, Sun-Mi; Gönen, Mithat; Vu, Ly; Minuesa, Gerard; Tivnan, Patrick; Barlowe, Trevor S.; Taggart, James; Lu, Yuheng; Deering, Raquel P.; Hacohen, Nir; Figueroa, Maria E.; Paietta, Elisabeth; Fernandez, Hugo F.; Tallman, Martin S.; Melnick, Ari; Levine, Ross; Leslie, Christina; Lengner, Christopher J.; Kharas, Michael G.

2015-01-01

Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model. Gene expression profiling of these Msi2-deficient animals revealed a loss of the hematopoietic/leukemic stem cell self-renewal program and an increase in the differentiation program. In acute myeloid leukemia patients, the presence of a gene signature that was similar to that observed in Msi2-deficent murine LSCs correlated with improved survival. We determined that MSI2 directly maintains the mixed-lineage leukemia (MLL) self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc, and Ikzf2 mRNAs. Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation, and increased apoptosis. Our data provide evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and suggest MSI2 as a potential therapeutic target for myeloid leukemia. PMID:25664853

Skull ecomorphology of megaherbivorous dinosaurs from the dinosaur park formation (upper campanian) of Alberta, Canada.

PubMed

Mallon, Jordan C; Anderson, Jason S

2013-01-01

Megaherbivorous dinosaur coexistence on the Late Cretaceous island continent of Laramidia has long puzzled researchers, owing to the mystery of how so many large herbivores (6-8 sympatric species, in many instances) could coexist on such a small (4-7 million km(2)) landmass. Various explanations have been put forth, one of which-dietary niche partitioning-forms the focus of this study. Here, we apply traditional morphometric methods to the skulls of megaherbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta to infer the ecomorphology of these animals and to test the niche partitioning hypothesis. We find evidence for niche partitioning not only among contemporaneous ankylosaurs, ceratopsids, and hadrosaurids, but also within these clades at the family and subfamily levels. Consubfamilial ceratopsids and hadrosaurids differ insignificantly in their inferred ecomorphologies, which may explain why they rarely overlap stratigraphically: interspecific competition prevented their coexistence.

Skull Ecomorphology of Megaherbivorous Dinosaurs from the Dinosaur Park Formation (Upper Campanian) of Alberta, Canada

PubMed Central

Mallon, Jordan C.; Anderson, Jason S.

2013-01-01

Megaherbivorous dinosaur coexistence on the Late Cretaceous island continent of Laramidia has long puzzled researchers, owing to the mystery of how so many large herbivores (6–8 sympatric species, in many instances) could coexist on such a small (4–7 million km2) landmass. Various explanations have been put forth, one of which–dietary niche partitioning–forms the focus of this study. Here, we apply traditional morphometric methods to the skulls of megaherbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta to infer the ecomorphology of these animals and to test the niche partitioning hypothesis. We find evidence for niche partitioning not only among contemporaneous ankylosaurs, ceratopsids, and hadrosaurids, but also within these clades at the family and subfamily levels. Consubfamilial ceratopsids and hadrosaurids differ insignificantly in their inferred ecomorphologies, which may explain why they rarely overlap stratigraphically: interspecific competition prevented their coexistence. PMID:23874409

The Dinosaur Connection.

ERIC Educational Resources Information Center

Donovan, Christine S.

1988-01-01

Provides background information, lesson plans, bulletin board activities, and a learning center description, all dealing with dinosaurs. Includes clip art for the learning center and reproducible "stamps" about some endangered species. (TW)

Redundant miR-3077-5p and miR-705 mediate the shift of mesenchymal stem cell lineage commitment to adipocyte in osteoporosis bone marrow.

PubMed

Liao, L; Yang, X; Su, X; Hu, C; Zhu, X; Yang, N; Chen, X; Shi, S; Shi, S; Jin, Y

2013-04-18

During the process of aging, especially for postmenopausal females, the cell lineage commitment of mesenchymal stem cells (MSCs) shift to adipocyte in bone marrow, resulting in osteoporosis. However, the cell-intrinsic mechanism of this cell lineage commitment switch is poorly understood. As the post-transcription regulation by microRNAs (miRNAs) has a critical role in MSCs differentiation and bone homeostasis, we performed comprehensive miRNAs profiling and found miR-705 and miR-3077-5p were significantly enhanced in MSCs from osteoporosis bone marrow. Both miR-705 and miR-3077-5p acted as inhibitors of MSCs osteoblast differentiation and promoters of adipocyte differentiation, by targeting on the 3'untranslated region (3'UTR) of HOXA10 and RUNX2 mRNA separately. Combined inhibition of miR-705 and miR-3077-5p rescued the cell lineage commitment disorder of MSCs through restoring HOXA10 and RUNX2 protein level. Furthermore, we found excessive TNFα and reactive oxygen species caused by estrogen deficiency led to the upregulation of both miRNAs through NF-κB pathway. In conclusion, our findings showed that redundant miR-705 and miR-3077-5p synergistically mediated the shift of MSCs cell lineage commitment to adipocyte in osteoporosis bone marrow, providing new insight into the etiology of osteoporosis at the post-transcriptional level. Moreover, the rescue of MSCs lineage commitment disorder by regulating miRNAs expression suggested a novel potential therapeutic target for osteoporosis as well as stem cell-mediated regenerative medicine.

Broad-Scale Patterns of Late Jurassic Dinosaur Paleoecology

PubMed Central

Noto, Christopher R.; Grossman, Ari

2010-01-01

Background There have been numerous studies on dinosaur biogeographic distribution patterns. However, these distribution data have not yet been applied to ecological questions. Ecological studies of dinosaurs have tended to focus on reconstructing individual taxa, usually through comparisons to modern analogs. Fewer studies have sought to determine if the ecological structure of fossil assemblages is preserved and, if so, how dinosaur communities varied. Climate is a major component driving differences between communities. If the ecological structure of a fossil locality is preserved, we expect that dinosaur assemblages from similar environments will share a similar ecological structure. Methodology/Principal Findings This study applies Ecological Structure Analysis (ESA) to a dataset of 100+ dinosaur taxa arranged into twelve composite fossil assemblages from around the world. Each assemblage was assigned a climate zone (biome) based on its location. Dinosaur taxa were placed into ecomorphological categories. The proportion of each category creates an ecological profile for the assemblage, which were compared using cluster and principal components analyses. Assemblages grouped according to biome, with most coming from arid or semi-arid/seasonal climates. Differences between assemblages are tied to the proportion of large high-browsing vs. small ground-foraging herbivores, which separates arid from semi-arid and moister environments, respectively. However, the effects of historical, taphonomic, and other environmental factors are still evident. Conclusions/Significance This study is the first to show that the general ecological structure of Late Jurassic dinosaur assemblages is preserved at large scales and can be assessed quantitatively. Despite a broad similarity of climatic conditions, a degree of ecological variation is observed between assemblages, from arid to moist. Taxonomic differences between Asia and the other regions demonstrate at least one case of

Broad-scale patterns of late jurassic dinosaur paleoecology.

PubMed

Noto, Christopher R; Grossman, Ari

2010-09-03

There have been numerous studies on dinosaur biogeographic distribution patterns. However, these distribution data have not yet been applied to ecological questions. Ecological studies of dinosaurs have tended to focus on reconstructing individual taxa, usually through comparisons to modern analogs. Fewer studies have sought to determine if the ecological structure of fossil assemblages is preserved and, if so, how dinosaur communities varied. Climate is a major component driving differences between communities. If the ecological structure of a fossil locality is preserved, we expect that dinosaur assemblages from similar environments will share a similar ecological structure. This study applies Ecological Structure Analysis (ESA) to a dataset of 100+ dinosaur taxa arranged into twelve composite fossil assemblages from around the world. Each assemblage was assigned a climate zone (biome) based on its location. Dinosaur taxa were placed into ecomorphological categories. The proportion of each category creates an ecological profile for the assemblage, which were compared using cluster and principal components analyses. Assemblages grouped according to biome, with most coming from arid or semi-arid/seasonal climates. Differences between assemblages are tied to the proportion of large high-browsing vs. small ground-foraging herbivores, which separates arid from semi-arid and moister environments, respectively. However, the effects of historical, taphonomic, and other environmental factors are still evident. This study is the first to show that the general ecological structure of Late Jurassic dinosaur assemblages is preserved at large scales and can be assessed quantitatively. Despite a broad similarity of climatic conditions, a degree of ecological variation is observed between assemblages, from arid to moist. Taxonomic differences between Asia and the other regions demonstrate at least one case of ecosystem convergence. The proportion of different ecomorphs, which

The myoseptal system in Chimaera monstrosa: collagenous fiber architecture and its evolution in the gnathostome stem lineage.

PubMed

Gemballa, Sven; Hagen, Katja

2004-01-01

Recent studies have revealed the 3D morphology and collagen fiber architecture of myosepta in teleostome fishes. Here we present the first data set on the myoseptal structure of a representative of the chondrichthyan clade. We investigate the series of myosepta in the ratfish Chimaera monstrosa (Holocephali) from the anterior to the posterior body using microdissections of cleared and stained specimens, polarized light microscopy of excised myosepta, and histology. The features of the myoseptal system of Chimaera are compared to data from closely related vertebrate groups and are mapped onto a phylogenetic tree to further clarify the characteristics of the myoseptal series in the gnathostome ancestor. The 3D morphology and collagen fiber architecture of the myoseptal series in C. monstrosa resembles that of Teleostomi (Actinopterygii+Sarcopterygii) with regard to several features. Our comparative analysis reveals that some of them have evolved in the gnathostome stem lineage. (1) A series of epineural and epaxial lateral tendons (LTs) along the whole body, and a series of epipleural and hypaxial LTs in the postanal region evolved in the gnathostome stem lineage. (2) The LTs increase in length towards the posterior body (three-fold in Chimaera). Data on Chimaera and some comparative data on actinopterygian fishes indicate that LTs also increase in thickness towards the posterior body, but further data are necessary to test whether this holds true generally. (3) Another conspicuous apomorphic gnathostome feature is represented by multi-layer structures of myosepta. These are formed along the vertebral column by converging medial regions of successive sloping parts of myosepta. (4) The dorsalmost and ventralmost flanking parts of myosepta bear a set of mediolaterally oriented collagen fibers that are present in all gnathostomes but are lacking in outgroups. Preanal hypaxial myosepta are clearly different from epaxial myosepta and postanal hypaxial myosepta in terms of

Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy.

PubMed

Yap, May Shin; Tang, Yin Quan; Yeo, Yin; Lim, Wei Ling; Lim, Lee Wei; Tan, Kuan Onn; Richards, Mark; Othman, Iekhsan; Poh, Chit Laa; Heng, Boon Chin

2016-01-06

The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials. This study thus investigated whether neural lineages derived from pluripotent human embryonic stem cells (hESC) can fulfil this purpose. EV71 infection of hESC-derived neural stem cells (NSC) and mature neurons (MN) was carried out in vitro, in comparison with RD and SH-SY5Y cell lines. Upon assessment of post-infection survivability and EV71 production by the various types, it was observed that NSC were significantly more susceptible to EV71 infection compared to MN, RD (rhabdomyosarcoma) and SH-SY5Y cells, which was consistent with previous studies on mice. The SP81 peptide had significantly greater inhibitory effect on EV71 production by NSC and MN compared to the cancer-derived RD and SH-SY5Y cell lines. Hence, this study demonstrates that hESC-derived neural lineages can be utilized as in vitro models for studying EV71 pathogenesis and for screening of antiviral therapeutics.

mSEL-1L deficiency affects vasculogenesis and neural stem cell lineage commitment.

PubMed

Cardano, Marina; Diaferia, Giuseppe R; Conti, Luciano; Baronchelli, Simona; Sessa, Alessandro; Broccoli, Vania; Barbieri, Andrea; De Blasio, Pasquale; Biunno, Ida

2018-04-01

mSEL-1L is a highly conserved ER-resident type I protein, involved in the degradation of misfolded peptides through the ubiquitin-proteasome system (UPS), a pathway known to control the plasticity of the vascular smooth muscle cells (VSMC) phenotype and survival. In this article, we demonstrate that mSEL-1L deficiency interferes with the murine embryonic vascular network, showing particular irregularities in the intracranic and intersomitic neurovascular units and in the cerebral capillary microcirculation. During murine embryogenesis, mSEL-1L is expressed in cerebral areas known to harbor progenitor neural cells, while in the adult brain the protein is specifically restricted to the stem cell niches, co-localizing with Sox2 and Nestin. Null mice are characterized by important defects in the development of telenchephalic regions, revealing conspicuous aberration in neural stem cell lineage commitment. Moreover, mSEL-1L depletion in vitro and in vivo appears to affect the harmonic differentiation of the NSCs, by negatively influencing the corticogenesis processes. Overall, the data presented suggests that the drastic phenotypic characteristics exhibited in mSEL-1L null mice can, in part, be explained by the negative influence it plays on Notch1 signaling pathway. © 2017 Wiley Periodicals, Inc.

Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor Cells in Tendon.

PubMed

Chen, Jialin; Zhang, Erchen; Zhang, Wei; Liu, Zeyu; Lu, Ping; Zhu, Ting; Yin, Zi; Backman, Ludvig J; Liu, Huanhuan; Chen, Xiao; Ouyang, Hongwei

2017-11-01

Stem cells have been widely used in tendon tissue engineering. The lack of refined and controlled differentiation strategy hampers the tendon repair and regeneration. This study aimed to find new effective differentiation factors for stepwise tenogenic differentiation. By microarray screening, the transcript factor Fos was found to be expressed in significantly higher amounts in postnatal Achilles tendon tissue derived from 1 day as compared with 7-days-old rats. It was further confirmed that expression of Fos decreased with time in postnatal rat Achilles tendon, which was accompanied with the decreased expression of multiply tendon markers. The expression of Fos also declined during regular in vitro cell culture, which corresponded to the loss of tendon phenotype. In a cell-sheet and a three-dimensional cell culture model, the expression of Fos was upregulated as compared with in regular cell culture, together with the recovery of tendon phenotype. In addition, significant higher expression of tendon markers was found in Fos-overexpressed tendon stem/progenitor cells (TSPCs), and Fos knock-down gave opposite results. In situ rat tendon repair experiments found more normal tendon-like tissue formed and higher tendon markers expression at 4 weeks postimplantation of Fos-overexpressed TSPCs derived nonscaffold engineering tendon (cell-sheet), as compared with the control group. This study identifies Fos as a new marker and functional driver in the early stage teno-lineage differentiation of tendon, which paves the way for effective stepwise tendon differentiation and future tendon regeneration. Stem Cells Translational Medicine 2017;6:2009-2019. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

36 CFR 7.63 - Dinosaur National Monument.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Dinosaur National Monument. 7.63 Section 7.63 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.63 Dinosaur National Monument. (a) Commercial...

Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

PubMed

Lu, Chenggang; Fuller, Margaret T

2015-12-01

Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell Lineages.

PubMed

Komarova, Natalia L; van den Driessche, P

2018-05-01

Design principles of biological networks have been studied extensively in the context of protein-protein interaction networks, metabolic networks, and regulatory (transcriptional) networks. Here we consider regulation networks that occur on larger scales, namely the cell-to-cell signaling networks that connect groups of cells in multicellular organisms. These are the feedback loops that orchestrate the complex dynamics of cell fate decisions and are necessary for the maintenance of homeostasis in stem cell lineages. We focus on "minimal" networks that are those that have the smallest possible numbers of controls. For such minimal networks, the number of controls must be equal to the number of compartments, and the reducibility/irreducibility of the network (whether or not it can be split into smaller independent sub-networks) is defined by a matrix comprised of the cell number increments induced by each of the controlled processes in each of the compartments. Using the formalism of digraphs, we show that in two-compartment lineages, reducible systems must contain two 1-cycles, and irreducible systems one 1-cycle and one 2-cycle; stability follows from the signs of the controls and does not require magnitude restrictions. In three-compartment systems, irreducible digraphs have a tree structure or have one 3-cycle and at least two more shorter cycles, at least one of which is a 1-cycle. With further work and proper biological validation, our results may serve as a first step toward an understanding of ways in which these networks become dysregulated in cancer.

Mechanical Modulation of Nascent Stem Cell Lineage Commitment in Tissue Engineering Scaffolds

PubMed Central

Song, Min Jae; Dean, David; Tate, Melissa L. Knothe

2013-01-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to “map the mechanome”, defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. PMID:23660249

Vision in dinosaurs: Scaling effects in sclerotic rings

NASA Astrophysics Data System (ADS)

Lee, Scott

Sclerotic rings are composed of bones found in the eyes of most vertebrates except mammals and crocodilians. They are believed to have a role in maintaining the shape of the eye. Their inner diameter is an upper limit for the effective diameter of the pupil and, therefore, provides a measure of the light-gathering ability of the eyes of extinct animals. Thirty-six different species of dinosaurs (from both the Saurischian and Ornithischian branches) have been studied. The smallest dinosaurs, with masses less than 1 kg, include Juravenator starki, Archaeopteryx lithographica, and Mei long while the largest dinosaurs, with masses on the order of 10,000 kg, include Diplodocus longus and Nemegtosaurus mongoliensis. The light-gathering properties of the eyes of the dinosaurs are studied as a function of the mass. The sclerotic ring diameter is found to increase with mass.

Pathologic bone tissues in a Turkey vulture and a nonavian dinosaur: implications for interpreting endosteal bone and radial fibrolamellar bone in fossil dinosaurs.

PubMed

Chinsamy, Anusuya; Tumarkin-Deratzian, Allison

2009-09-01

We report on similar pathological bone microstructure in an extant turkey vulture (Cathartes aura) and a nonavian dinosaur from Transylvania. Both these individuals exhibit distinctive periosteal reactive bone deposition accompanied by endosteal bone deposits in the medullary cavity. Our findings have direct implications on the two novel bone tissues recently described among nonavian dinosaurs, radial fibrolamellar bone tissue and medullary bone tissue. On the basis of the observed morphology of the periosteal reactive bone in the turkey vulture and the Transylvanian dinosaur, we propose that the radial fibrolamellar bone tissues observed in mature dinosaurs may have had a pathological origin. Our analysis also shows that on the basis of origin, location, and morphology, pathologically derived endosteal bone tissue can be similar to medullary bone tissues described in nonavian dinosaurs. As such, we caution the interpretation of all endosteally derived bone tissue as homologous to avian medullary bone. (c) 2009 Wiley-Liss, Inc.

A theropod dinosaur embryo and the affinities of the flaming cliffs dinosaur eggs.

PubMed

Norell, M A; Clark, J M; Demberelyin, D; Rhinchen, B; Chiappe, L M; Davidson, A R; McKenna, M C; Altangerel, P; Novacek, M J

1994-11-04

An embryonic skeleton of a nonavian theropod dinosaur was found preserved in an egg from Upper Cretaceous rocks in the Gobi Desert of Mongolia. Cranial features identify the embryo as a member of Oviraptoridae. Two embryo-sized skulls of dromaeosaurids, similar to that of Velociraptor, were also recovered in the nest. The eggshell microstructure is similar to that of ratite birds and is of a type common in the Djadokhta Formation at the Flaming Cliffs (Bayn Dzak). Discovery of a nest of such eggs at the Flaming Cliffs in 1923, beneath the Oviraptor philoceratops holotype, suggests that this dinosaur may have been a brooding adult.

A basal dinosaur from the dawn of the dinosaur era in southwestern Pangaea.

PubMed

Martinez, Ricardo N; Sereno, Paul C; Alcober, Oscar A; Colombi, Carina E; Renne, Paul R; Montañez, Isabel P; Currie, Brian S

2011-01-14

Upper Triassic rocks in northwestern Argentina preserve the most complete record of dinosaurs before their rise to dominance in the Early Jurassic. Here, we describe a previously unidentified basal theropod, reassess its contemporary Eoraptor as a basal sauropodomorph, divide the faunal record of the Ischigualasto Formation with biozones, and bracket the formation with (40)Ar/(39)Ar ages. Some 230 million years ago in the Late Triassic (mid Carnian), the earliest dinosaurs were the dominant terrestrial carnivores and small herbivores in southwestern Pangaea. The extinction of nondinosaurian herbivores is sequential and is not linked to an increase in dinosaurian diversity, which weakens the predominant scenario for dinosaurian ascendancy as opportunistic replacement.

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

PubMed Central

Dorantes-Acosta, Elisa; Pelayo, Rosana

2012-01-01

Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development. PMID:22852088

Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

PubMed

Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

2017-10-19

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

Respiratory and reproductive paleophysiology of dinosaurs and early birds.

PubMed

Ruben, John A; Jones, Terry D; Geist, Nicholas R

2003-01-01

In terms of their diversity and longevity, dinosaurs and birds were/are surely among the most successful of terrestrial vertebrates. Unfortunately, interpreting many aspects of the biology of dinosaurs and the earliest of the birds presents formidable challenges because they are known only from fossils. Nevertheless, a variety of attributes of these taxa can be inferred by identification of shared anatomical structures whose presence is causally linked to specialized functions in living reptiles, birds, and mammals. Studies such as these demonstrate that although dinosaurs and early birds were likely to have been homeothermic, the absence of nasal respiratory turbinates in these animals indicates that they were likely to have maintained reptile-like (ectothermic) metabolic rates during periods of rest or routine activity. Nevertheless, given the metabolic capacities of some extant reptiles during periods of elevated activity, early birds were probably capable of powered flight. Similarly, had, for example, theropod dinosaurs possessed aerobic metabolic capacities and habits equivalent to those of some large, modern tropical latitude lizards (e.g., Varanus), they may well have maintained significant home ranges and actively pursued and killed large prey. Additionally, this scenario of active, although ectothermic, theropod dinosaurs seems reinforced by the likely utilization of crocodilian-like, diaphragm breathing in this group. Finally, persistent in vivo burial of their nests and apparent lack of egg turning suggests that clutch incubation by dinosaurs was more reptile- than birdlike. Contrary to previous suggestions, there is little if any reliable evidence that some dinosaur young may have been helpless and nestbound (altricial) at hatching.

Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia

PubMed Central

Wei, Junping; Wunderlich, Mark; Fox, Catherine; Alvarez, Sara; Cigudosa, Juan C.; Wilhelm, Jamie S.; Zheng, Yi; Cancelas, Jose A.; Gu, Yi; Jansen, Michael; DiMartino, Jorge F.; Mulloy, James C.

2008-01-01

Summary Faithful modeling of mixed lineage leukemia in murine cells has been difficult to achieve. We show that expression of MLL-AF9 in human CD34+ cells induces acute myeloid, lymphoid or mixed lineage leukemia in immunodeficient mice. Some leukemia stem cells (LSC) were multipotent and could be lineage directed by altering either the growth factors or the recipient strain of mouse, highlighting the importance of microenviromental cues. Other LSC were strictly lineage committed, demonstrating the heterogeneity of the stem cell compartment in MLL disease. Targeting the Rac signaling pathway by pharmacologic or genetic means resulted in rapid and specific apoptosis of MLL-AF9 cells, suggesting that the Rac signaling pathway may be a valid therapeutic target in MLL-rearranged AML. PMID:18538732

Sexual maturity in growing dinosaurs does not fit reptilian growth models

PubMed Central

Lee, Andrew H.; Werning, Sarah

2008-01-01

Recent histological studies suggest relatively rapid growth in dinosaurs. However, the timing of reproductive maturity (RM) in dinosaurs is poorly known because unambiguous indicators of RM are rare. One exception is medullary bone (MB), which is an ephemeral bony tissue that forms before ovulation in the marrow cavities of birds as a calcium source for eggshelling. Recently, MB also was described in a single specimen of the saurischian dinosaur Tyrannosaurus rex. Here, we report two other occurrences of MB: in another saurischian dinosaur, Allosaurus, and in the ornithischian dinosaur Tenontosaurus. We show by counting lines of arrested growth and performing growth curve reconstructions that Tenontosaurus, Allosaurus, and Tyrannosaurus were reproductively mature by 8, 10, and 18 years, respectively. RM in these dinosaurs coincided with a transition from growth acceleration to deceleration. It also far precedes predictions based on the growth rates of living reptiles scaled to similar size. Despite relatively rapid growth, dinosaurs were similar to reptiles in that RM developed before reaching asymptotic size. However, this reproductive strategy also occurs in medium- to large-sized mammals and correlates with a strategy of prolonged multiyear growth. RM in actively growing individuals suggests that these dinosaurs were born relatively precocial and experienced high adult mortality. The origin of the modern avian reproductive strategy in ornithuran birds likely coincided with their extreme elevations in growth rate and truncations to growth duration. PMID:18195356

Sexual maturity in growing dinosaurs does not fit reptilian growth models.

PubMed

Lee, Andrew H; Werning, Sarah

2008-01-15

Recent histological studies suggest relatively rapid growth in dinosaurs. However, the timing of reproductive maturity (RM) in dinosaurs is poorly known because unambiguous indicators of RM are rare. One exception is medullary bone (MB), which is an ephemeral bony tissue that forms before ovulation in the marrow cavities of birds as a calcium source for eggshelling. Recently, MB also was described in a single specimen of the saurischian dinosaur Tyrannosaurus rex. Here, we report two other occurrences of MB: in another saurischian dinosaur, Allosaurus, and in the ornithischian dinosaur Tenontosaurus. We show by counting lines of arrested growth and performing growth curve reconstructions that Tenontosaurus, Allosaurus, and Tyrannosaurus were reproductively mature by 8, 10, and 18 years, respectively. RM in these dinosaurs coincided with a transition from growth acceleration to deceleration. It also far precedes predictions based on the growth rates of living reptiles scaled to similar size. Despite relatively rapid growth, dinosaurs were similar to reptiles in that RM developed before reaching asymptotic size. However, this reproductive strategy also occurs in medium- to large-sized mammals and correlates with a strategy of prolonged multiyear growth. RM in actively growing individuals suggests that these dinosaurs were born relatively precocial and experienced high adult mortality. The origin of the modern avian reproductive strategy in ornithuran birds likely coincided with their extreme elevations in growth rate and truncations to growth duration.

Robust Differentiation of mRNA-Reprogrammed Human Induced Pluripotent Stem Cells Toward a Retinal Lineage.

PubMed

Sridhar, Akshayalakshmi; Ohlemacher, Sarah K; Langer, Kirstin B; Meyer, Jason S

2016-04-01

The derivation of human induced pluripotent stem cells (hiPSCs) from patient-specific sources has allowed for the development of novel approaches to studies of human development and disease. However, traditional methods of generating hiPSCs involve the risks of genomic integration and potential constitutive expression of pluripotency factors and often exhibit low reprogramming efficiencies. The recent description of cellular reprogramming using synthetic mRNA molecules might eliminate these shortcomings; however, the ability of mRNA-reprogrammed hiPSCs to effectively give rise to retinal cell lineages has yet to be demonstrated. Thus, efforts were undertaken to test the ability and efficiency of mRNA-reprogrammed hiPSCs to yield retinal cell types in a directed, stepwise manner. hiPSCs were generated from human fibroblasts via mRNA reprogramming, with parallel cultures of isogenic human fibroblasts reprogrammed via retroviral delivery of reprogramming factors. New lines of mRNA-reprogrammed hiPSCs were established and were subsequently differentiated into a retinal fate using established protocols in a directed, stepwise fashion. The efficiency of retinal differentiation from these lines was compared with retroviral-derived cell lines at various stages of development. On differentiation, mRNA-reprogrammed hiPSCs were capable of robust differentiation to a retinal fate, including the derivation of photoreceptors and retinal ganglion cells, at efficiencies often equal to or greater than their retroviral-derived hiPSC counterparts. Thus, given that hiPSCs derived through mRNA-based reprogramming strategies offer numerous advantages owing to the lack of genomic integration or constitutive expression of pluripotency genes, such methods likely represent a promising new approach for retinal stem cell research, in particular, those for translational applications. In the current report, the ability to derive mRNA-reprogrammed human induced pluripotent stem cells (hi

Forearm posture and mobility in quadrupedal dinosaurs.

PubMed

VanBuren, Collin S; Bonnan, Matthew

2013-01-01

Quadrupedality evolved four independent times in dinosaurs; however, the constraints associated with these transitions in limb anatomy and function remain poorly understood, in particular the evolution of forearm posture and rotational ability (i.e., active pronation and supination). Results of previous qualitative studies are inconsistent, likely due to an inability to quantitatively assess the likelihood of their conclusions. We attempt to quantify antebrachial posture and mobility using the radius bone because its morphology is distinct between extant sprawled taxa with a limited active pronation ability and parasagittal taxa that have an enhanced ability to actively pronate the manus. We used a sliding semi-landmark, outline-based geometric morphometric approach of the proximal radial head and a measurement of the angle of curvature of the radius in a sample of 189 mammals, 49 dinosaurs, 35 squamates, 16 birds, and 5 crocodilians. Our results of radial head morphology showed that quadrupedal ceratopsians, bipedal non-hadrosaurid ornithopods, and theropods had limited pronation/supination ability, and sauropodomorphs have unique radial head morphology that likely allowed limited rotational ability. However, the curvature of the radius showed that no dinosaurian clade had the ability to cross the radius about the ulna, suggesting parallel antebrachial elements for all quadrupedal dinosaurs. We conclude that the bipedal origins of all quadrupedal dinosaur clades could have allowed for greater disparity in forelimb posture than previously appreciated, and future studies on dinosaur posture should not limit their classifications to the overly simplistic extant dichotomy.

Forearm Posture and Mobility in Quadrupedal Dinosaurs

PubMed Central

VanBuren, Collin S.; Bonnan, Matthew

2013-01-01

Quadrupedality evolved four independent times in dinosaurs; however, the constraints associated with these transitions in limb anatomy and function remain poorly understood, in particular the evolution of forearm posture and rotational ability (i.e., active pronation and supination). Results of previous qualitative studies are inconsistent, likely due to an inability to quantitatively assess the likelihood of their conclusions. We attempt to quantify antebrachial posture and mobility using the radius bone because its morphology is distinct between extant sprawled taxa with a limited active pronation ability and parasagittal taxa that have an enhanced ability to actively pronate the manus. We used a sliding semi-landmark, outline-based geometric morphometric approach of the proximal radial head and a measurement of the angle of curvature of the radius in a sample of 189 mammals, 49 dinosaurs, 35 squamates, 16 birds, and 5 crocodilians. Our results of radial head morphology showed that quadrupedal ceratopsians, bipedal non-hadrosaurid ornithopods, and theropods had limited pronation/supination ability, and sauropodomorphs have unique radial head morphology that likely allowed limited rotational ability. However, the curvature of the radius showed that no dinosaurian clade had the ability to cross the radius about the ulna, suggesting parallel antebrachial elements for all quadrupedal dinosaurs. We conclude that the bipedal origins of all quadrupedal dinosaur clades could have allowed for greater disparity in forelimb posture than previously appreciated, and future studies on dinosaur posture should not limit their classifications to the overly simplistic extant dichotomy. PMID:24058633

"Dinosaurs." Kindergarten. Anchorage School District Elementary Science Program.

ERIC Educational Resources Information Center

Herminghaus, Trisha, Ed.

This unit contains 15 lessons on dinosaurs for kindergarten children. It provides a materials list, supplementary materials list, use of process skill terminology, unit objectives, vocabulary, six major dinosaurs, and background information. Lessons are: (1) "Webbing"; (2) "Introduction to the Big Six"; (3) "Paleontology…

Diversity patterns amongst herbivorous dinosaurs and plants during the Cretaceous: implications for hypotheses of dinosaur/angiosperm co-evolution.

PubMed

Butler, R J; Barrett, P M; Kenrick, P; Penn, M G

2009-03-01

Palaeobiologists frequently attempt to identify examples of co-evolutionary interactions over extended geological timescales. These hypotheses are often intuitively appealing, as co-evolution is so prevalent in extant ecosystems, and are easy to formulate; however, they are much more difficult to test than their modern analogues. Among the more intriguing deep time co-evolutionary scenarios are those that relate changes in Cretaceous dinosaur faunas to the primary radiation of flowering plants. Demonstration of temporal congruence between the diversifications of co-evolving groups is necessary to establish whether co-evolution could have occurred in such cases, but is insufficient to prove whether it actually did take place. Diversity patterns do, however, provide a means for falsifying such hypotheses. We have compiled a new database of Cretaceous dinosaur and plant distributions from information in the primary literature. This is used as the basis for plotting taxonomic diversity and occurrence curves for herbivorous dinosaurs (Sauropodomorpha, Stegosauria, Ankylosauria, Ornithopoda, Ceratopsia, Pachycephalosauria and herbivorous theropods) and major groups of plants (angiosperms, Bennettitales, cycads, cycadophytes, conifers, Filicales and Ginkgoales) that co-occur in dinosaur-bearing formations. Pairwise statistical comparisons were made between various floral and faunal groups to test for any significant similarities in the shapes of their diversity curves through time. We show that, with one possible exception, diversity patterns for major groups of herbivorous dinosaurs are not positively correlated with angiosperm diversity. In other words, at the level of major clades, there is no support for any diffuse co-evolutionary relationship between herbivorous dinosaurs and flowering plants. The diversification of Late Cretaceous pachycephalosaurs (excluding the problematic taxon Stenopelix) shows a positive correlation, but this might be spuriously related to

Acute leukemias of ambiguous lineage.

PubMed

Béné, Marie C; Porwit, Anna

2012-02-01

The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called "leukemias of ambiguous lineage." The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chromosome BCR-ABL1 or involvement of the MLL gene on chromosome 11q23. Other MPAL are divided into B/myeloid NOS, T/myeloid NOS, B/T NOS, and B/T/myeloid NOS. MPAL are usually of dire prognosis, respond variably to chemotherapy of acute lymphoblastic or acute myeloblastic type, and benefit most from rapid allogeneic hematopoietic stem cell transplantation.

Inferring rules of lineage commitment in haematopoiesis.

PubMed

Pina, Cristina; Fugazza, Cristina; Tipping, Alex J; Brown, John; Soneji, Shamit; Teles, Jose; Peterson, Carsten; Enver, Tariq

2012-02-19

How the molecular programs of differentiated cells develop as cells transit from multipotency through lineage commitment remains unexplored. This reflects the inability to access cells undergoing commitment or located in the immediate vicinity of commitment boundaries. It remains unclear whether commitment constitutes a gradual process, or else represents a discrete transition. Analyses of in vitro self-renewing multipotent systems have revealed cellular heterogeneity with individual cells transiently exhibiting distinct biases for lineage commitment. Such systems can be used to molecularly interrogate early stages of lineage affiliation and infer rules of lineage commitment. In haematopoiesis, population-based studies have indicated that lineage choice is governed by global transcriptional noise, with self-renewing multipotent cells reversibly activating transcriptome-wide lineage-affiliated programs. We examine this hypothesis through functional and molecular analysis of individual blood cells captured from self-renewal cultures, during cytokine-driven differentiation and from primary stem and progenitor bone marrow compartments. We show dissociation between self-renewal potential and transcriptome-wide activation of lineage programs, and instead suggest that multipotent cells experience independent activation of individual regulators resulting in a low probability of transition to the committed state.

Cloning from stem cells: different lineages, different species, same story.

PubMed

Oback, Björn

2009-01-01

Following nuclear transfer (NT), the most stringent measure of extensive donor cell reprogramming is development into viable offspring. This is referred to as cloning efficiency and quantified as the proportion of cloned embryos transferred into surrogate mothers that survive into adulthood. Cloning efficiency depends on the ability of the enucleated recipient cell to carry out the reprogramming reactions ('reprogramming ability') and the ability of the nuclear donor cell to be reprogrammed ('reprogrammability'). It has been postulated that reprogrammability of the somatic donor cell epigenome is inversely proportional to its differentiation status. In order to test this hypothesis, reprogrammability was compared between undifferentiated stem cells and their differentiated isogenic progeny. In the mouse, cells of divergent differentiation status from the neuronal, haematopoietic and skin epithelial lineage were tested. In cattle and deer, skeletal muscle and antler cells, respectively, were used as donors. No conclusive correlation between differentiation status and cloning efficiency was found, indicating that somatic donor cell type may not be the limiting factor for cloning success. This may reflect technical limitations of the NT-induced reprogramming assay. Alternatively, differentiation status and reprogrammability may be unrelated, making all cells equally difficult to reprogramme once they have left the ground state of pluripotency.

First complete sauropod dinosaur skull from the Cretaceous of the Americas and the evolution of sauropod dentition.

PubMed

Chure, Daniel; Britt, Brooks B; Whitlock, John A; Wilson, Jeffrey A

2010-04-01

Sauropod dinosaur bones are common in Mesozoic terrestrial sediments, but sauropod skulls are exceedingly rare--cranial materials are known for less than one third of sauropod genera and even fewer are known from complete skulls. Here we describe the first complete sauropod skull from the Cretaceous of the Americas, Abydosaurus mcintoshi, n. gen., n. sp., known from 104.46 +/- 0.95 Ma (megannum) sediments from Dinosaur National Monument, USA. Abydosaurus shares close ancestry with Brachiosaurus, which appeared in the fossil record ca. 45 million years earlier and had substantially broader teeth. A survey of tooth shape in sauropodomorphs demonstrates that sauropods evolved broad crowns during the Early Jurassic but did not evolve narrow crowns until the Late Jurassic, when they occupied their greatest range of crown breadths. During the Cretaceous, brachiosaurids and other lineages independently underwent a marked diminution in tooth breadth, and before the latest Cretaceous broad-crowned sauropods were extinct on all continental landmasses. Differential survival and diversification of narrow-crowned sauropods in the Late Cretaceous appears to be a directed trend that was not correlated with changes in plant diversity or abundance, but may signal a shift towards elevated tooth replacement rates and high-wear dentition. Sauropods lacked many of the complex herbivorous adaptations present within contemporaneous ornithischian herbivores, such as beaks, cheeks, kinesis, and heterodonty. The spartan design of sauropod skulls may be related to their remarkably small size--sauropod skulls account for only 1/200th of total body volume compared to 1/30th body volume in ornithopod dinosaurs.

DENTAL PULP STEM CELLS AND HUMAN PERIAPICAL CYST MESENCHYMAL STEM CELLS IN BONE TISSUE REGENERATION: COMPARISON OF BASAL AND OSTEOGENIC DIFFERENTIATED GENE EXPRESSION OF A NEWLY DISCOVERED MESENCHYMAL STEM CELL LINEAGE.

PubMed

Tatullo, M; Falisi, G; Amantea, M; Rastelli, C; Paduano, F; Marrelli, M

2015-01-01

Bone regeneration is an interesting field of biomedicine. The most recent studies are aimed to achieve a bone regeneration using mesenchymal stem cells (MSCs) taken from more accessible sites: oral and dental tissues have been widely investigated as a rich accessible source of MSCs. Dental Pulp Stem Cells (DPSCs) and human Periapical Cysts Mesenchymal Stem Cells (hPCy-MSCs) represent the new generation MSCs. The aim of this study is to compare the gene expression of these two innovative cell types to highlight the advantages of their use in bone regeneration. The harvesting, culturing and differentiating of cells isolated from dental pulp as well as from periapical cystic tissue were carried out as described in previously published reports. qRT-PCR analyses were performed on osteogenic genes in undifferentiated and osteogenic differentiated cells of DPSC and hPCy-MSC lineage. Real-time RT-PCR data suggested that both DPSCs and hPCy-MSCs cultured in osteogenic media are able to differentiate into osteoblast/odontoblast-like cells: however, some differences indicated that DPSCs seem to be directed more towards dentinogenesis, while hPCy-MSCs seem to be directed more towards osteogenesis.

Embryonic metabolism of the ornithischian dinosaurs Protoceratops andrewsi and Hypacrosaurus stebingeri and implications for calculations of dinosaur egg incubation times

NASA Astrophysics Data System (ADS)

Lee, Scott A.

2017-04-01

The embryonic metabolisms of the ornithischian dinosaurs Protoceratops andrewsi and Hypacrosaurus stebingeri have been determined and are in the range observed in extant reptiles. The average value of the measured embryonic metabolic rates for P. andrewsi and H. stebingeri are then used to calculate the incubation times for 21 dinosaurs from both Sauischia and Ornithischia using a mass growth model based on conservation of energy. The calculated incubation times vary from about 70 days for Archaeopteryx lithographica to about 180 days for Alamosaurus sanjuanensis. Such long incubation times seem unlikely, particularly for the sauropods and large theropods. Incubation times are also predicted with the assumption that the saurischian dinosaurs had embryonic metabolisms in the range observed in extant birds.

Embryonic metabolism of the ornithischian dinosaurs Protoceratops andrewsi and Hypacrosaurus stebingeri and implications for calculations of dinosaur egg incubation times.

PubMed

Lee, Scott A

2017-04-01

The embryonic metabolisms of the ornithischian dinosaurs Protoceratops andrewsi and Hypacrosaurus stebingeri have been determined and are in the range observed in extant reptiles. The average value of the measured embryonic metabolic rates for P. andrewsi and H. stebingeri are then used to calculate the incubation times for 21 dinosaurs from both Sauischia and Ornithischia using a mass growth model based on conservation of energy. The calculated incubation times vary from about 70 days for Archaeopteryx lithographica to about 180 days for Alamosaurus sanjuanensis. Such long incubation times seem unlikely, particularly for the sauropods and large theropods. Incubation times are also predicted with the assumption that the saurischian dinosaurs had embryonic metabolisms in the range observed in extant birds.

Cockroaches probably cleaned up after dinosaurs.

PubMed

Vršanský, Peter; van de Kamp, Thomas; Azar, Dany; Prokin, Alexander; Vidlička, L'ubomír; Vagovič, Patrik

2013-01-01

Dinosaurs undoubtedly produced huge quantities of excrements. But who cleaned up after them? Dung beetles and flies with rapid development were rare during most of the Mesozoic. Candidates for these duties are extinct cockroaches (Blattulidae), whose temporal range is associated with herbivorous dinosaurs. An opportunity to test this hypothesis arises from coprolites to some extent extruded from an immature cockroach preserved in the amber of Lebanon, studied using synchrotron X-ray microtomography. 1.06% of their volume is filled by particles of wood with smooth edges, in which size distribution directly supports their external pre-digestion. Because fungal pre-processing can be excluded based on the presence of large particles (combined with small total amount of wood) and absence of damages on wood, the likely source of wood are herbivore feces. Smaller particles were broken down biochemically in the cockroach hind gut, which indicates that the recent lignin-decomposing termite and cockroach endosymbionts might have been transferred to the cockroach gut upon feeding on dinosaur feces.

Piscivory in the feathered dinosaur Microraptor.

PubMed

Xing, Lida; Persons, W Scott; Bell, Phil R; Xu, Xing; Zhang, Jianping; Miyashita, Tetsuto; Wang, Fengping; Currie, Philip J

2013-08-01

The largest specimen of the four-winged dromaeosaurid dinosaur Microraptor gui includes preserved gut contents. Previous reports of gut contents and considerations of functional morphology have indicated that Microraptor hunted in an arboreal environment. The new specimen demonstrates that this was not strictly the case, and offers unique insights into the ecology of nonavian dinosaurs early in the evolution of flight. The preserved gut contents are composed of teleost fish remains. Several morphological adaptations of Microraptor are identified as consistent with a partially piscivorous diet, including dentition with reduced serrations and forward projecting teeth on the anterior of the dentary. The feeding habits of Microraptor can now be understood better than that of any other carnivorous nonavian dinosaur, and Microraptor appears to have been an opportunistic and generalist feeder, able to exploit the most common prey in both the arboreal and aquatic microhabitats of the Early Cretaceous Jehol ecosystem. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Gideon Mantell and the Discovery of Dinosaurs

NASA Astrophysics Data System (ADS)

Dean, Dennis R.

1999-01-01

Gideon Mantell and the Discovery of Dinosaurs is a scholarly yet accessible biography--the first in a generation--of a pioneering dinosaur hunter and scholar. Gideon Mantell discovered the Iguanodon (a famous tale set right in this book) and several other dinosaur species, spent over twenty-five years restoring Iguanodon fossils, and helped establish the idea of an Age of Reptiles that ended with their extinction at the conclusion of the Mesozoic Era. He had significant interaction with such well-known figures as James Parkinson, Georges Cuvier, Charles Lyell, Roderick Murchison, Charles Darwin, and Richard Owen. Dennis Dean, a well-known scholar of geology and the Victorian era, here places Mantell's career in its cultural context, employing original research in archives throughout the world, including the previously unexamined Mantell family papers in New Zealand.

Haematopoietic stem and progenitor cells from human pluripotent stem cells

PubMed Central

Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

2018-01-01

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

Dental Disparity and Ecological Stability in Bird-like Dinosaurs prior to the End-Cretaceous Mass Extinction.

PubMed

Larson, Derek W; Brown, Caleb M; Evans, David C

2016-05-23

The causes, rate, and selectivity of the end-Cretaceous mass extinction continue to be highly debated [1-5]. Extinction patterns in small, feathered maniraptoran dinosaurs (including birds) are important for understanding extant biodiversity and present an enigma considering the survival of crown group birds (Neornithes) and the extinction of their close kin across the end-Cretaceous boundary [6]. Because of the patchy Cretaceous fossil record of small maniraptorans [7-12], this important transition has not been closely examined in this group. Here, we test the hypothesis that morphological disparity in bird-like dinosaurs was decreasing leading up to the end-Cretaceous mass extinction, as has been hypothesized in some dinosaurs [13, 14]. To test this, we examined tooth morphology, an ecological indicator in fossil reptiles [15-19], from over 3,100 maniraptoran teeth from four groups (Troodontidae, Dromaeosauridae, Richardoestesia, and cf. Aves) across the last 18 million years of the Cretaceous. We demonstrate that tooth disparity, a proxy for variation in feeding ecology, shows no significant decline leading up to the extinction event within any of the groups. Tooth morphospace occupation also remains static over this time interval except for increased size during the early Maastrichtian. Our data provide strong support that extinction within this group occurred suddenly after a prolonged period of ecological stability. To explain this sudden extinction of toothed maniraptorans and the survival of Neornithes, we propose that diet may have been an extinction filter and suggest that granivory associated with an edentulous beak was a key ecological trait in the survival of some lineages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnesium and extinction of dinosaurs. Was magnesium deficit a major cause?

PubMed

Durlach, J

1991-01-01

Chinese researchers have recently demonstrated that, before the extinction of dinosaurs, there was an impressive lowering in the magnesium concentration of fossil dinosaur eggshell. The structural and functional importance of eggshell magnesium--mainly in the cone layer--for embryonic viability and hatchability of oviparous species supports the hypothesis that magnesium deficit may have had a direct role in dinosaur extinction. Conversely this low magnesium concentration seems a questionable marker of magnesium deficit. The natural forces involved in the extinction of dinosaurs are more likely to induce magnesium depletion than magnesium deficiency. These very interesting preliminary data call for further research.

Regional and stage-specific effects of prospectively purified vascular cells on the adult V-SVZ neural stem cell lineage.

PubMed

Crouch, Elizabeth E; Liu, Chang; Silva-Vargas, Violeta; Doetsch, Fiona

2015-03-18

Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contribution of pericytes to the neural stem cell niche has not been defined. Here, we describe a rapid FACS purification strategy to simultaneously isolate primary endothelial cells and pericytes from brain microregions of nontransgenic mice using CD31 and CD13 as surface markers. We compared the effect of purified vascular cells from a neurogenic (V-SVZ) and non-neurogenic brain region (cortex) on the V-SVZ stem cell lineage in vitro. Endothelial and pericyte diffusible signals from both regions differentially promote the proliferation and neuronal differentiation of qNSCs, aNSCs, and TACs. Unexpectedly, diffusible cortical signals had the most potent effects on V-SVZ proliferation and neurogenesis, highlighting the intrinsic capacity of non-neurogenic vasculature to support stem cell behavior. Finally, we identify PlGF-2 as an endothelial-derived mitogen that promotes V-SVZ cell proliferation. This purification strategy provides a platform to define the functional and molecular contribution of vascular cells to stem cell niches and other brain regions under different physiological and pathological states. Copyright © 2015 the authors 0270-6474/15/354528-12$15.00/0.

Comment on "Evidence for mesothermy in dinosaurs".

PubMed

D'Emic, M D

2015-05-29

Grady et al. (Reports, 13 June 2014, p. 1268) suggested that nonavian dinosaur metabolism was neither endothermic nor ectothermic but an intermediate physiology termed "mesothermic." However, rates were improperly scaled and phylogenetic, physiological, and temporal categories of animals were conflated during analyses. Accounting for these issues suggests that nonavian dinosaurs were on average as endothermic as extant placental mammals. Copyright © 2015, American Association for the Advancement of Science.

Paleobiological implications of dinosaur egg-bearing deposits in the Cretaceous Gyeongsang Supergroup of Korea

NASA Astrophysics Data System (ADS)

Paik, In Sung; Kim, Hyun Joo; Huh, Min

2010-05-01

Dinosaur egg-bearing deposits in the Cretaceous Gyeongsang Basin in Korea is described in taphonomic aspect, their paleoenvironments are interpreted, and geobiological implications of dinosaur egg-bearing deposits in the world and Korea are analyzed in geographic occurrences, geological ages, paleoenvironments, and lithology. Dinosaur eggs with spheroolithids, faveoloolithid, and elongatoolithid structural types occur in several stratigraphic formations of the Cretaceous Gyeongsang Basin in South Korea, and most of the egg-bearing formations are the Late Cretaceous. The dinosaur eggs usually occur as clutches in purple sandy mudstone of floodplain deposits preserved as calcic paleosol with association of vertic paleosol features in places. Most of the eggs are top-broken and filled with surrounding sediments. The general depositional environment of dinosaur egg deposits in the Gyeongsang Supergroup are interpreted as a dried floodplain where volcanic activity occurred intermittently in the vicinity of the nesting sites. Their depositional settings on which floodplains developed are diverse from fluvial plain with meandering rivers to alluvial plain with episodic sheet flooding. The nesting areas in the Gyeongsang Basin are deemed to have been under semi-arid climate, which resulted in formation of calcic soils facilitating preservation of the dinosaur eggs. The geochronologic occurrences of dinosaur egg-bearing deposits are mostly restricted to the Late Cretaceous in the world as well as in Korea. If it has not been resulted from biased discoveries and reports of dinosaur eggs, biological rather than physical and chemical conditions for preservation of dinosaur eggs might be related with the restricted occurrences in the Late Cretaceous. Two hypotheses are suggested for probable biological causes to the geochronologically restricted occurrences of dinosaur egg-bearing deposits. One is related with the appearance of angiosperms in the Late Jurassic and the spreading

Dinosaur or Phoenix: Nuclear Bombers in the 21st Century

DTIC Science & Technology

2010-04-12

REPORT DATE 02-04-10 2. REPORT TYPE Master’s Thesis 3. DATES COVERED 31-07-09 to 16-06-10 4. TITLE AND SUBTITLE Dinosaur or Phoenix: Nuclear...WARFIGHTING SCHOOL DINOSAUR OR PHOENIX: NUCLEAR BOMBERS IN THE 21ST CENTURY by John W. Morehead Colonel, United States Air Force A paper...can argue Secretary Gates’ decision to halt development of a follow-on bomber indicates the DOD views nuclear bombers as dinosaurs no longer needed as

There Could Be a Dinosaur in Your Life!

ERIC Educational Resources Information Center

Jacob, Beth; Dempsey, Bill

This booklet describes how to make large two-dimensional models of dinosaur skeletons which can be effective teaching tools. Small laminated wood dinosaur models are enlarged, traced, and transferred to tri-wall cardboard (one-half inch thick) and cut out with a saber saw. Parts are then slotted and numbered for easy assembly. The result is a kit…

Temporal and phylogenetic evolution of the sauropod dinosaur body plan

NASA Astrophysics Data System (ADS)

Bates, Karl T.; Mannion, Philip D.; Falkingham, Peter L.; Brusatte, Stephen L.; Hutchinson, John R.; Otero, Alejandro; Sellers, William I.; Sullivan, Corwin; Stevens, Kent A.; Allen, Vivian

2016-03-01

The colossal size and body plan of sauropod dinosaurs are unparalleled in terrestrial vertebrates. However, to date, there have been only limited attempts to examine temporal and phylogenetic patterns in the sauropod bauplan. Here, we combine three-dimensional computational models with phylogenetic reconstructions to quantify the evolution of whole-body shape and body segment properties across the sauropod radiation. Limitations associated with the absence of soft tissue preservation in fossils result in large error bars about mean absolute body shape predictions. However, applying any consistent skeleton : body volume ratio to all taxa does yield changes in body shape that appear concurrent with major macroevolutionary events in sauropod history. A caudad shift in centre-of-mass (CoM) in Middle Triassic Saurischia, associated with the evolution of bipedalism in various dinosaur lineages, was reversed in Late Triassic sauropodomorphs. A craniad CoM shift coincided with the evolution of quadrupedalism in the Late Triassic, followed by a more striking craniad shift in Late Jurassic-Cretaceous titanosauriforms, which included the largest sauropods. These craniad CoM shifts are strongly correlated with neck enlargement, a key innovation in sauropod evolution and pivotal to their gigantism. By creating a much larger feeding envelope, neck elongation is thought to have increased feeding efficiency and opened up trophic niches that were inaccessible to other herbivores. However, we find that relative neck size and CoM position are not strongly correlated with inferred feeding habits. Instead the craniad CoM positions of titanosauriforms appear closely linked with locomotion and environmental distributions, potentially contributing to the continued success of this group until the end-Cretaceous, with all other sauropods having gone extinct by the early Late Cretaceous.

Fossilized melanosomes and the colour of Cretaceous dinosaurs and birds.

PubMed

Zhang, Fucheng; Kearns, Stuart L; Orr, Patrick J; Benton, Michael J; Zhou, Zhonghe; Johnson, Diane; Xu, Xing; Wang, Xiaolin

2010-02-25

Spectacular fossils from the Early Cretaceous Jehol Group of northeastern China have greatly expanded our knowledge of the diversity and palaeobiology of dinosaurs and early birds, and contributed to our understanding of the origin of birds, of flight, and of feathers. Pennaceous (vaned) feathers and integumentary filaments are preserved in birds and non-avian theropod dinosaurs, but little is known of their microstructure. Here we report that melanosomes (colour-bearing organelles) are not only preserved in the pennaceous feathers of early birds, but also in an identical manner in integumentary filaments of non-avian dinosaurs, thus refuting recent claims that the filaments are partially decayed dermal collagen fibres. Examples of both eumelanosomes and phaeomelanosomes have been identified, and they are often preserved in life position within the structure of partially degraded feathers and filaments. Furthermore, the data here provide empirical evidence for reconstructing the colours and colour patterning of these extinct birds and theropod dinosaurs: for example, the dark-coloured stripes on the tail of the theropod dinosaur Sinosauropteryx can reasonably be inferred to have exhibited chestnut to reddish-brown tones.

Mountain building triggered late cretaceous North American megaherbivore dinosaur radiation.

PubMed

Gates, Terry A; Prieto-Márquez, Albert; Zanno, Lindsay E

2012-01-01

Prior studies of Mesozoic biodiversity document a diversity peak for dinosaur species in the Campanian stage of the Late Cretaceous, yet have failed to provide explicit causal mechanisms. We provide evidence that a marked increase in North American dinosaur biodiversity can be attributed to dynamic orogenic episodes within the Western Interior Basin (WIB). Detailed fossil occurrences document an association between the shift from Sevier-style, latitudinally arrayed basins to smaller Laramide-style, longitudinally arrayed basins and a well substantiated decreased geographic range/increased taxonomic diversity of megaherbivorous dinosaur species. Dispersal-vicariance analysis demonstrates that the nearly identical biogeographic histories of the megaherbivorous dinosaur clades Ceratopsidae and Hadrosauridae are attributable to rapid diversification events within restricted basins and that isolation events are contemporaneous with known tectonic activity in the region. SymmeTREE analysis indicates that megaherbivorous dinosaur clades exhibited significant variation in diversification rates throughout the Late Cretaceous. Phylogenetic divergence estimates of fossil clades offer a new lower boundary on Laramide surficial deformation that precedes estimates based on sedimentological data alone.

Mountain Building Triggered Late Cretaceous North American Megaherbivore Dinosaur Radiation

PubMed Central

Gates, Terry A.; Prieto-Márquez, Albert; Zanno, Lindsay E.

2012-01-01

Prior studies of Mesozoic biodiversity document a diversity peak for dinosaur species in the Campanian stage of the Late Cretaceous, yet have failed to provide explicit causal mechanisms. We provide evidence that a marked increase in North American dinosaur biodiversity can be attributed to dynamic orogenic episodes within the Western Interior Basin (WIB). Detailed fossil occurrences document an association between the shift from Sevier-style, latitudinally arrayed basins to smaller Laramide-style, longitudinally arrayed basins and a well substantiated decreased geographic range/increased taxonomic diversity of megaherbivorous dinosaur species. Dispersal-vicariance analysis demonstrates that the nearly identical biogeographic histories of the megaherbivorous dinosaur clades Ceratopsidae and Hadrosauridae are attributable to rapid diversification events within restricted basins and that isolation events are contemporaneous with known tectonic activity in the region. SymmeTREE analysis indicates that megaherbivorous dinosaur clades exhibited significant variation in diversification rates throughout the Late Cretaceous. Phylogenetic divergence estimates of fossil clades offer a new lower boundary on Laramide surficial deformation that precedes estimates based on sedimentological data alone. PMID:22876302

Effects of Ionizing Radiation on Human Adipose Derived Mesenchymal Stem Cells and their Differentiation towards the Osteoblastic Lineage

NASA Astrophysics Data System (ADS)

Konda, Bikash; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther; Lau, Patrick

Radiation exposure and musculoskeletal disuse are among the major challenges during space missions. Astronauts face the problem to lose bone calcium due to uncoupling of bone formation and resorption. Bone forming osteoblasts can be derived from the undifferentiated mesenchymal stem cell compartment (MSC). In this study, the ability of human adipose tissue derived stem cells (ATSC) to differentiate into the osteoblastic lineage was examined after radiation exposure in presence of medium supplementation with osteogenic additives (ß-glycerophosphate, ascorbic acid and dexamethasone). The SAOS-2 cell line (human osteosarcoma cell line) was used as control for osteoblastic differentiation. Changes in cellular morphology, cell cycle progression, as well as cellular radiation sensitivity were characterized after ionizing radiation exposure with X-rays and heavy ions (Ti). Rapidly proliferating SAOS-2 cells are less radiation-sensitive than slowly proliferating ATSC cells after X-ray (CFA: dose effect curves show D0 values of 1 Gy and 0.75 Gy for SAOS-2 and ATSC, respectively) exposure. Heavy ion (Ti) exposure resulted in a greater extent of cells accumulating in the G2/M phase of the cell cycle in a dose-dependent manner when compared to X-ray exposure. Differentiation of cells towards the osteoblastic lineage was quantified by hydroxyapatite (HA) deposition using Lonza OsteoImageTM mineralization assay. The deposition of HA after X- and Ti-irradiation for highly proliferating SAOS-2 cells showed a dose-dependent time delay while slowly proliferating ATSC showed no effect from radiation exposure. More detailed investigation is required to reveal the radiation dependent mechanism of bone loss in astronauts.

Does morphological convergence imply functional similarity? A test using the evolution of quadrupedalism in ornithischian dinosaurs.

PubMed

Maidment, Susannah C R; Barrett, Paul M

2012-09-22

Convergent morphologies are thought to indicate functional similarity, arising because of a limited number of evolutionary or developmental pathways. Extant taxa displaying convergent morphologies are used as analogues to assess function in extinct taxa with similar characteristics. However, functional studies of extant taxa have shown that functional similarity can arise from differing morphologies, calling into question the paradigm that form and function are closely related. We test the hypothesis that convergent skeletal morphology indicates functional similarity in the fossil record using ornithischian dinosaurs. The rare transition from bipedality to quadrupedality occurred at least three times independently in this clade, resulting in a suite of convergent osteological characteristics. We use homology rather than analogy to provide an independent line of evidence about function, reconstructing soft tissues using the extant phylogenetic bracket and applying biomechanical concepts to produce qualitative assessments of muscle leverage. We also optimize character changes to investigate the sequence of character acquisition. Different lineages of quadrupedal ornithischian dinosaur stood and walked differently from each other, falsifying the hypothesis that osteological convergence indicates functional similarity. The acquisition of features correlated with quadrupedalism generally occurs in the same order in each clade, suggesting underlying developmental mechanisms that act as evolutionary constraints.

Kinematics from a 163 Million-Year-Old Dinosaur Trackway

NASA Astrophysics Data System (ADS)

Lee, Scott

2011-10-01

Dinosaurs always grab the interest of students. Information about dinosaur locomotion is accessible from the trackways they left. In a unique connection to kinematics, evidence of the acceleration of a meat-eating dinosaur (theropod) is evident in Trackway 13 in Ardley Quarry in Oxfordshire, UK. This particular trackway is described by J.J. Day, D.B. Norman, P. Upchuch and H.P. Powell in Vol. 415 of Nature on pages 494 and 495, published in 2002. This particular theropod underwent an acceleration of about g/3. This example provides a fun and engaging exercise for students studying kinematics.

Reworking of Cretaceous dinosaurs into Paleocene channel deposits, upper Hell Creek Formation, Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lofgren, D.L.; Hotton, C.L.; Runkel, A.C.

1990-09-01

Dinosaur teeth from Paleocene channel fills have been interpreted as indicating dinosaur survival into the Paleocene. However, enormous potential for reworking exists because these records are restricted to large channel fills that are deeply incised into Cretaceous strata. Identification of reworked fossils is usually equivocal. This problem is illustrated by the Black Spring Coulee channel fill, a dinosaur-bearing Paleocene deposit in the upper Hell Creek Formation of eastern Montana. In this example, the reworked nature of well-preserved dinosaur bones is apparent only after detailed sedimentological and palynological analysis. Because of the potential for reworking, dinosaur remains derived from Paleocene fluvialmore » deposits should not be assigned a Paleocene age unless the (1) are found in floodplain deposits, (2) are articulated, (3) are in channels that do not incise Cretaceous strata, or (4) are demonstrably reworked from Paleocene deposits. To date, reports of Paleocene dinosaurs do not fulfill any of these criteria. Thus, the proposal that dinosaurs persisted into the Paleocene remains unsubstantiated.« less

Preservation of the bone protein osteocalcin in dinosaurs

NASA Astrophysics Data System (ADS)

Muyzer, Gerard; Sandberg, Philip; Knapen, Marjo H. J.; Vermeer, Cees; Collins, Matthew; Westbroek, Peter

1992-10-01

Two different immunological assays were used to identify the remains of a bone matrix protein, osteocalcin (OC), in the bones of dinosaurs and other fossil vertebrates. Antibodies raised against OC from modern vertebrates showed strong immunological cross-reactivity with modern and relatively young fossil samples and significant reactions with some of the dinosaur bone extracts. The presence of OC was confirmed by the detection of a peptide-bound, uniquely vertebrate amino acid, γcarboxyglutamic acid (Gla). Preservation of OC in fossil bones appears to be strongly dependent on the burial history and not simply on age. These results extend the range of protein preservation in the geologic record and provide a first step toward a molecular phylogeny of the dinosaurs.

Cockroaches Probably Cleaned Up after Dinosaurs

PubMed Central

Vršanský, Peter; van de Kamp, Thomas; Azar, Dany; Prokin, Alexander; Vidlička, L'ubomír; Vagovič, Patrik

2013-01-01

Dinosaurs undoubtedly produced huge quantities of excrements. But who cleaned up after them? Dung beetles and flies with rapid development were rare during most of the Mesozoic. Candidates for these duties are extinct cockroaches (Blattulidae), whose temporal range is associated with herbivorous dinosaurs. An opportunity to test this hypothesis arises from coprolites to some extent extruded from an immature cockroach preserved in the amber of Lebanon, studied using synchrotron X-ray microtomography. 1.06% of their volume is filled by particles of wood with smooth edges, in which size distribution directly supports their external pre-digestion. Because fungal pre-processing can be excluded based on the presence of large particles (combined with small total amount of wood) and absence of damages on wood, the likely source of wood are herbivore feces. Smaller particles were broken down biochemically in the cockroach hind gut, which indicates that the recent lignin-decomposing termite and cockroach endosymbionts might have been transferred to the cockroach gut upon feeding on dinosaur feces. PMID:24324610

New dinosaur (Theropoda, stem-Averostra) from the earliest Jurassic of the La Quinta formation, Venezuelan Andes

PubMed Central

Langer, Max C.; Rincón, Ascanio D.; Ramezani, Jahandar; Solórzano, Andrés; Rauhut, Oliver W. M.

2014-01-01

Dinosaur skeletal remains are almost unknown from northern South America. One of the few exceptions comes from a small outcrop in the northernmost extension of the Andes, along the western border of Venezuela, where strata of the La Quinta Formation have yielded the ornithischian Laquintasaura venezuelae and other dinosaur remains. Here, we report isolated bones (ischium and tibia) of a small new theropod, Tachiraptor admirabilis gen. et sp. nov., which differs from all previously known members of the group by an unique suite of features of its tibial articulations. Comparative/phylogenetic studies place the new form as the sister taxon to Averostra, a theropod group that is known primarily from the Middle Jurassic onwards. A new U–Pb zircon date (isotope dilution thermal-ionization mass spectrometry; ID-TIMS method) from the bone bed matrix suggests an earliest Jurassic maximum age for the La Quinta Formation. A dispersal–vicariance analysis suggests that such a stratigraphic gap is more likely to be filled by new records from north and central Pangaea than from southern areas. Indeed, our data show that the sampled summer-wet equatorial belt, which yielded the new taxon, played a pivotal role in theropod evolution across the Triassic–Jurassic boundary. PMID:26064540

New dinosaur (Theropoda, stem-Averostra) from the earliest Jurassic of the La Quinta formation, Venezuelan Andes.

PubMed

Langer, Max C; Rincón, Ascanio D; Ramezani, Jahandar; Solórzano, Andrés; Rauhut, Oliver W M

2014-10-01

Dinosaur skeletal remains are almost unknown from northern South America. One of the few exceptions comes from a small outcrop in the northernmost extension of the Andes, along the western border of Venezuela, where strata of the La Quinta Formation have yielded the ornithischian Laquintasaura venezuelae and other dinosaur remains. Here, we report isolated bones (ischium and tibia) of a small new theropod, Tachiraptor admirabilis gen. et sp. nov., which differs from all previously known members of the group by an unique suite of features of its tibial articulations. Comparative/phylogenetic studies place the new form as the sister taxon to Averostra, a theropod group that is known primarily from the Middle Jurassic onwards. A new U-Pb zircon date (isotope dilution thermal-ionization mass spectrometry; ID-TIMS method) from the bone bed matrix suggests an earliest Jurassic maximum age for the La Quinta Formation. A dispersal-vicariance analysis suggests that such a stratigraphic gap is more likely to be filled by new records from north and central Pangaea than from southern areas. Indeed, our data show that the sampled summer-wet equatorial belt, which yielded the new taxon, played a pivotal role in theropod evolution across the Triassic-Jurassic boundary.

Genetic Lineage Tracing of Non-Myocyte Population by Dual Recombinases.

PubMed

Li, Yan; He, Lingjuan; Huang, Xiuzhen; Issa Bhaloo, Shirin; Zhao, Huan; Zhang, Shaohua; Pu, Wenjuan; Tian, Xueying; Li, Yi; Liu, Qiaozhen; Yu, Wei; Zhang, Libo; Liu, Xiuxiu; Liu, Kuo; Tang, Juan; Zhang, Hui; Cai, Dongqing; Adams, Ralf H; Xu, Qingbo; Lui, Kathy O; Zhou, Bin

2018-04-26

Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1 + , Bmi1 + , Isl1 + or Abcg2 + CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart. Methods -To address this question without relying on a particular stem cell marker, we developed a new genetic lineage tracing system to label all non-myocyte populations that contain putative CSCs. Using dual lineage tracing system, we assessed if non-myocytes generated any new myocytes during embryonic development, adult homeostasis and after myocardial infarction. Skeletal muscle was also examined after injury for internal control of new myocytes generation from non-myocytes. Results -By this stem cell marker-free and dual recombinases-mediated cell tracking approach, our fate mapping data show that new myocytes arise from non-myocytes in the embryonic heart, but not in the adult heart during homeostasis or after myocardial infarction. As positive control, our lineage tracing system detected new myocytes derived from non-myocytes in the skeletal muscle after injury. Conclusions -This study provides in vivo genetic evidence for non-myocyte to myocyte conversion in embryonic but not adult heart, arguing again the myogenic potential of putative stem cell populations for cardiac regeneration in the adult stage. This study also provides a new genetic strategy to identify endogenous stem cells, if any, in other organ systems for tissue repair and regeneration.

Oxygen isotopes from biogenic apatites suggest widespread endothermy in Cretaceous dinosaurs

NASA Astrophysics Data System (ADS)

Amiot, Romain; Lécuyer, Christophe; Buffetaut, Eric; Escarguel, Gilles; Fluteau, Frédéric; Martineau, François

2006-06-01

The much debated question of dinosaur thermophysiology has not yet been conclusively solved despite numerous attempts. We used the temperature-dependent oxygen isotope fractionation between vertebrate body water (δ 18O body water) and phosphatic tissues (δ 18O p) to compare the thermophysiology of dinosaurs with that of non-dinosaurian ectothermic reptiles. Present-day δ 18O p values of vertebrate apatites show that ectotherms have higher δ 18O p values than endotherms at high latitudes due to their lower body temperature, and conversely lower δ 18O p values than endotherms at low latitudes. Using a data set of 80 new and 49 published δ 18O p values, we observed similar and systematic differences in δ 18O p values (Δ 18O) between four groups of Cretaceous dinosaurs (theropods, sauropods, ornithopods and ceratopsians) and associated fresh water crocodiles and turtles. Expressed in terms of body temperatures ( Tb), these Δ 18O values indicate that dinosaurs maintained rather constant Tb in the range of endotherms whatever ambient temperatures were. This implies that high metabolic rates were widespread among Cretaceous dinosaurs belonging to widely different taxonomic groups and suggest that endothermy may be a synapomorphy of dinosaurs, or may have been acquired convergently in the studied taxa.

Dinosaur trackways from the early Late Cretaceous of western Cameroon

NASA Astrophysics Data System (ADS)

Martin, Jeremy E.; Menkem, Elie Fosso; Djomeni, Adrien; Fowe, Paul Gustave; Ntamak-Nida, Marie-Joseph

2017-10-01

Dinosaur trackways have rarely been reported in Cretaceous strata across the African continent. To the exception of ichnological occurrences in Morocco, Tunisia, Niger and Cameroon, our knowledge on the composition of Cretaceous dinosaur faunas mostly relies on skeletal evidence. For the first time, we document several dinosaur trackways from the Cretaceous of the Mamfe Basin in western Cameroon. Small and medium-size tridactyl footprints as well as numerous large circular footprints are present on a single horizon showing mudcracks and ripple marks. The age of the locality is considered Cenomanian-Turonian and if confirmed, this ichnological assemblage could be younger than the dinosaur footprints reported from northern Cameroon, and coeval with or younger than skeletal remains reported from the Saharan region. These trackways were left in an adjacent subsiding basin along the southern shore of the Benue Trough during a time of high-sea stand when the Trans-Saharan Seaway was already disconnecting West Africa from the rest of the continent. We predict that other similar track sites may be occurring along the margin of the Benue Trough and may eventually permit to test hypotheses related to provincialism among African dinosaur faunas.

76 FR 7232 - Notice of Inventory Completion: U.S. Department of the Interior, National Park Service, Dinosaur...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

.... Department of the Interior, National Park Service, Dinosaur National Monument, Dinosaur, CO AGENCY: National... Service, Dinosaur National Monument, Dinosaur, CO, has completed an inventory of human remains and... Indian tribe that believes itself to be culturally affiliated with the human remains may contact Dinosaur...

Gradual Dinosaur Extinction and Simultaneous Ungulate Radiation in the Hell Creek Formation

NASA Astrophysics Data System (ADS)

Sloan, Robert E.; Rigby, J. Keith; van Valen, Leigh M.; Gabriel, Diane

1986-05-01

Dinosaur extinction in Montana, Alberta, and Wyoming was a gradual process that began 7 million years before the end of the Cretaceous and accelerated rapidly in the final 0.3 million years of the Cretaceous, during the interval of apparent competition from rapidly evolving immigrating ungulates. This interval involves rapid reduction in both diversity and population density of dinosaurs. The last dinosaurs known are from a channel that contains teeth of Mantuan mammals, seven species of dinosaurs, and Paleocene pollen. The top of this channel is 1.3 meters above the likely position of the iridium anomaly, the Cretaceous/Tertiary boundary.

Warm and Cool Dinosaurs.

ERIC Educational Resources Information Center

Mannlein, Sally

2001-01-01

Presents an art activity in which first grade students draw dinosaurs in order to learn about the concept of warm and cool colors. Explains how the activity also helped the students learn about the concept of distance when drawing. (CMK)

Kindergartners Love Dinosaurs

ERIC Educational Resources Information Center

Stollon, Marcy

2005-01-01

In this article, the author relates how she uses an art lesson that integrates art, language arts, and science in an enjoyable, creative project about dinosaurs in her kindergarten class. She relates how the children enjoy being illustrators and becoming familiar with well-known children's illustrators. She also relates that she starts her classes…

Diachronism between extinction time of terrestrial and marine dinosaurs

NASA Technical Reports Server (NTRS)

Hansen, H. J.

1988-01-01

The dinosaur eggs of southern France occur in continental, fine-grained red-beds, rich in carbonate. The last eggs in the region occur in the magnetic polarity interval 30 normal. Estimates of the accumulation rate of these sediments on the basis of the magneto-stratigraphy leads to placement of the time of disappearance of the dinosaurs in this region of 200,000 to 400,000 years earlier than the Cretaceous-Tertiary boundary. In the Red Deer Valley, Canada, estimates of average accumulation rate lead to a time of disappearance of the dinosaurs of 135,000 to 157,000 years earlier than the Cretaceous-Tertiary boundary. In the central part of Poland, in the Nasilow Quarry, the paleomagnetic pattern shows 7 m of chalk of reversed polarity containing in its upper part the marine Cretaceous-Tertiary biostratigraphic boundary. A greensand deposit contains numerous re-deposited Maastrichtian fossils. The fossils show no signs of wear and are of very different sizes including 1 mm thick juvenile belemnites. The deposit was described as a lag-sediment. Among the various fossils are teeth of mosasaurs. Thus there is coincidence in time between the extinction of mosasaurs and other Cretaceous organisms. This leads to the conclusion, that extinction of terrestrial dinosaurs took place earlier than extinction of marine dinosaurs at the Cretaceous-Tertiary boundary.

A dinosaur missing-link? Chilesaurus and the early evolution of ornithischian dinosaurs.

PubMed

Baron, Matthew G; Barrett, Paul M

2017-08-01

The enigmatic dinosaur taxon Chilesaurus diegosuarezi was originally described as a tetanuran theropod, but this species possesses a highly unusual combination of features that could provide evidence of alternative phylogenetic positions within the clade. In order to test the relationships of Chilesaurus , we added it to a new dataset of early dinosaurs and other dinosauromorphs. Our analyses recover Chilesaurus in a novel position, as the earliest diverging member of Ornithischia, rather than a tetanuran theropod. The basal position of Chilesaurus within the clade and its suite of anatomical characters suggest that it might represent a 'transitional' taxon, bridging the morphological gap between Theropoda and Ornithischia, thereby offering potential insights into the earliest stages of ornithischian evolution, which were previously obscure. For example, our results suggest that pubic retroversion occurred prior to some of the craniodental and postcranial modifications that previously diagnosed the clade (e.g. the presence of a predentary bone and ossified tendons). © 2017 The Author(s).

Dinosaur Peptides Suggest Mechanisms of Protein Survival

PubMed Central

San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P. R. O.

2011-01-01

Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival. PMID:21687667

Dinosaur peptides suggest mechanisms of protein survival.

PubMed

San Antonio, James D; Schweitzer, Mary H; Jensen, Shane T; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P R O

2011-01-01

Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

Dinosaur Peptides Suggest Mechanisms of Protein Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.

Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results showmore » empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.« less

Tuning of major signaling networks (TGF-β, Wnt, Notch and Hedgehog) by miRNAs in human stem cells commitment to different lineages: Possible clinical application.

PubMed

Aval, Sedigheh Fekri; Lotfi, Hajie; Sheervalilou, Roghayeh; Zarghami, Nosratollah

2017-07-01

Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events. MicroRNAs (miRNAs) are cellular switches that modulate stem cells outcomes in response to diverse extracellular signals. Numerous scientific evidences implicating miRNAs in major signal transduction pathways highlight new crosstalks of cellular processes. Aberrant signaling pathways and miRNAs levels result in developmental defects and diverse human pathologies. This review discusses the crosstalk between the components of main signaling networks and the miRNA machinery, which plays a role in the context of stem cells development and provides a set of examples to illustrate the extensive relevance of potential novel therapeutic targets. Copyright © 2017. Published by Elsevier Masson SAS.

The history of dinosaur footprint discoveries in Wyoming with emphasis on the Bighorn Basin

USGS Publications Warehouse

Kvale, Erik P.; Mickelson, Debra L.; Hasiotis, Stephen T; Johnson, Gary D.

2003-01-01

Dinosaur traces are well known from the western United States in the Colorado Plateau region (Utah, Colorado, New Mexico, and Arizona). Utah contains the greatest abundance of known and documented dinosaur footprints and trackways. Far less well known, however, is the occurrence and distribution of dinosaur footprint-bearing horizons in Wyoming. Scientific studies over the past 10 years have shown that three of the four Middle and Upper Jurassic formations in northern Wyoming contain dinosaur footprints. Two of the footprint-bearing horizons are located in geologic intervals that were once thought to have been deposited in offshore to nearshore marine settings and represent rare North American examples of Middle Jurassic (Bajocian and Bathonian) dinosaur remains. Some of these new Wyoming sites can be correlated to known dinosaur footprint-bearing horizons or intervals in Utah. Wyoming has a great potential for additional discoveries of new dinosaur footprint-bearing horizons, and further prospecting and study is warranted and will ultimately lead to a much better understanding of the geographic distribution and behavior of the potential footprint-makers.

Sauropod dinosaurs evolved moderately sized genomes unrelated to body size.

PubMed

Organ, Chris L; Brusatte, Stephen L; Stein, Koen

2009-12-22

Sauropodomorph dinosaurs include the largest land animals to have ever lived, some reaching up to 10 times the mass of an African elephant. Despite their status defining the upper range for body size in land animals, it remains unknown whether sauropodomorphs evolved larger-sized genomes than non-avian theropods, their sister taxon, or whether a relationship exists between genome size and body size in dinosaurs, two questions critical for understanding broad patterns of genome evolution in dinosaurs. Here we report inferences of genome size for 10 sauropodomorph taxa. The estimates are derived from a Bayesian phylogenetic generalized least squares approach that generates posterior distributions of regression models relating genome size to osteocyte lacunae volume in extant tetrapods. We estimate that the average genome size of sauropodomorphs was 2.02 pg (range of species means: 1.77-2.21 pg), a value in the upper range of extant birds (mean = 1.42 pg, range: 0.97-2.16 pg) and near the average for extant non-avian reptiles (mean = 2.24 pg, range: 1.05-5.44 pg). The results suggest that the variation in size and architecture of genomes in extinct dinosaurs was lower than the variation found in mammals. A substantial difference in genome size separates the two major clades within dinosaurs, Ornithischia (large genomes) and Saurischia (moderate to small genomes). We find no relationship between body size and estimated genome size in extinct dinosaurs, which suggests that neutral forces did not dominate the evolution of genome size in this group.

Sauropod dinosaurs evolved moderately sized genomes unrelated to body size

PubMed Central

Organ, Chris L.; Brusatte, Stephen L.; Stein, Koen

2009-01-01

Sauropodomorph dinosaurs include the largest land animals to have ever lived, some reaching up to 10 times the mass of an African elephant. Despite their status defining the upper range for body size in land animals, it remains unknown whether sauropodomorphs evolved larger-sized genomes than non-avian theropods, their sister taxon, or whether a relationship exists between genome size and body size in dinosaurs, two questions critical for understanding broad patterns of genome evolution in dinosaurs. Here we report inferences of genome size for 10 sauropodomorph taxa. The estimates are derived from a Bayesian phylogenetic generalized least squares approach that generates posterior distributions of regression models relating genome size to osteocyte lacunae volume in extant tetrapods. We estimate that the average genome size of sauropodomorphs was 2.02 pg (range of species means: 1.77–2.21 pg), a value in the upper range of extant birds (mean = 1.42 pg, range: 0.97–2.16 pg) and near the average for extant non-avian reptiles (mean = 2.24 pg, range: 1.05–5.44 pg). The results suggest that the variation in size and architecture of genomes in extinct dinosaurs was lower than the variation found in mammals. A substantial difference in genome size separates the two major clades within dinosaurs, Ornithischia (large genomes) and Saurischia (moderate to small genomes). We find no relationship between body size and estimated genome size in extinct dinosaurs, which suggests that neutral forces did not dominate the evolution of genome size in this group. PMID:19793755

Temporal and phylogenetic evolution of the sauropod dinosaur body plan

PubMed Central

Bates, Karl T.; Mannion, Philip D.; Falkingham, Peter L.; Brusatte, Stephen L.; Hutchinson, John R.; Otero, Alejandro; Sellers, William I.; Sullivan, Corwin; Stevens, Kent A.; Allen, Vivian

2016-01-01

The colossal size and body plan of sauropod dinosaurs are unparalleled in terrestrial vertebrates. However, to date, there have been only limited attempts to examine temporal and phylogenetic patterns in the sauropod bauplan. Here, we combine three-dimensional computational models with phylogenetic reconstructions to quantify the evolution of whole-body shape and body segment properties across the sauropod radiation. Limitations associated with the absence of soft tissue preservation in fossils result in large error bars about mean absolute body shape predictions. However, applying any consistent skeleton : body volume ratio to all taxa does yield changes in body shape that appear concurrent with major macroevolutionary events in sauropod history. A caudad shift in centre-of-mass (CoM) in Middle Triassic Saurischia, associated with the evolution of bipedalism in various dinosaur lineages, was reversed in Late Triassic sauropodomorphs. A craniad CoM shift coincided with the evolution of quadrupedalism in the Late Triassic, followed by a more striking craniad shift in Late Jurassic–Cretaceous titanosauriforms, which included the largest sauropods. These craniad CoM shifts are strongly correlated with neck enlargement, a key innovation in sauropod evolution and pivotal to their gigantism. By creating a much larger feeding envelope, neck elongation is thought to have increased feeding efficiency and opened up trophic niches that were inaccessible to other herbivores. However, we find that relative neck size and CoM position are not strongly correlated with inferred feeding habits. Instead the craniad CoM positions of titanosauriforms appear closely linked with locomotion and environmental distributions, potentially contributing to the continued success of this group until the end-Cretaceous, with all other sauropods having gone extinct by the early Late Cretaceous. PMID:27069652

Cretaceous Vertebrate Tracksites - Korean Cretaceous Dinosaur Coast World Heritage Nomination Site

NASA Astrophysics Data System (ADS)

Huh, M.; Woo, K. S.; Lim, J. D.; Paik, I. S.

2009-04-01

South Korea is one of the best known regions in the world for Cretaceous fossil footprints, which are also world-renowned. Korea has produced more scientifically named bird tracks (ichnotaxa) than any other region in the world. It has also produced the world's largest pterosaur tracks. Dinosaur tracksites also have the highest frequency of vertebrate track-bearing levels currently known in any stratigraphic sequence. Among the areas that have the best track records, and the greatest scientific significance with best documentation, Korea ranks very highly. Objective analysis of important individual tracksites and tracksite regions must be based on multiple criteria including: size of site, number of tracks, trackways and track bearing levels, number of valid named ichnotaxa including types, number of scientific publications, quality of preservation. The unique and distinctive dinosaur tracksites are known as one of the world's most important dinosaur track localities. In particular, the dinosaur track sites in southern coastal area of Korea are very unique. In the sites, we have excavated over 10,000 dinosaur tracks. The Hwasun sites show diverse gaits with unusual walking patterns and postures in some tracks. The pterosaur tracks are the most immense in the world. The longest pterosaur trackway yet known from any track sites suggests that pterosaurs were competent terrestrial locomotors. This ichnofauna contains the first pterosaur tracks reported from Asia. The Haenam Uhangri pterosaur assigns to a new genus Haenamichnus which accomodates the new ichnospecies, Haenamichnus uhangriensis. At least 12 track types have been reported from the Haman and Jindong Formations (probably late Lower Cretaceous). These include the types of bird tracks assigned to Koreanornis, Jindongornipes, Ignotornis and Goseongornipes. In addition the bird tracks Hwangsanipes, Uhangrichnus, the pterosaur track Haenamichnus and the dinosaur tracks, Brontopodus, Caririchnium, Minisauripus and

The comparison of species longevity and size evolution in fossilized dinosaurs vs. fossilized mammals

NASA Astrophysics Data System (ADS)

Baeza, E.; Srinath, A.; Hernandez, A.; Heim, N.; Payne, J.

2016-12-01

For over 200 million years, two animal groups have been competing for dominance over Earth: the reptiles, (in this case, dinosaurs), and the mammals. At the beginning of the Triassic, mammals were small, rat-like creatures that were dwarfed by the dinosaurs. Dinosaurs progressively continued to grow larger throughout the Jurassic and Cretaceous periods, thus outweighing and outliving the current mammals. But at the end of the Cretaceous, the K-T mass extinction occurred, and that wiped out the dinosaurs from the face of the Earth. After the disappearance of dinosaurs, mammals started to grow larger to fill the niches that the dinosaurs left open. With this evolution in mammals, would they be able to match or even beat the dinosaur's previous records? To judge that, we need to utilize two significant factors to help judge our answer. The two factors that set them apart were body mass and longevity. Documenting the body mass shows us how much the animal weighed compared to other species. The heaviest animal in our data set weighed 77 tons. The other factor is longevity, which indicates how long a certain species has existed on a geologic time scale. The longest living animal species in our data set lived for over 20 million years. With all the data we have analyzed, we have conducted research on this subject to find out how terrestrial mammals contrasted dinosaurs in the terms of body mass and species longevity. Our research brought us to the conclusion that mammals could not overtake the body mass and longevity of dinosaurs. Although mammals came pretty close to overlapping the dinosaurs' body masses, they were just below them marginally. We had a similar pattern in longevity, where we found out that heavier animals tended to have longer longevity, therefore the dinosaurs came out on top. Additionally, we did another contrast between Mesozoic and Cenozoic mammals, where Cenozoic mammals were larger, but both had similar longevities.

Dinosaur demise in light of their alleged perennial polar residency

NASA Astrophysics Data System (ADS)

Lewy, Zeev

2017-10-01

The end-Cretaceous biological crisis is represented by the demise of the non-avian dinosaurs. However, most crucial biologically was the elimination of the photosynthesizing marine phyto- and zooplankton forming the base of the marine food chain. Their abrupt demise attests to sunlight screening darkening the atmosphere for a few years. Alvarez et al. (Science 208:1095-1108, 1980. doi: 10.1126/science.208.44) noticed in deep marine end-Cretaceous sediments an anomalous rise in the chemical element iridium (Ir), which is rare on planet Earth and thus suggests an extraterrestrial origin through an impact of a large asteroid. This impact would have ejected enormous quantities of particles and aerosols, shading the solar illumination as attested to by the elimination of the marine photosynthesizing plankton. Such a dark period must have affected life on land. The apparent cold-blooded non-avian dinosaurs, which were used to living in open terrains to absorb the solar illumination, became inactive during the dark period and were incapable of withstanding predators. This was in contrast to cold-blooded crocodilians, turtles and lizards that could hide in refuge sites on land and in the water. Dinosaur relics discovered in Cretaceous Polar Regions were attributed to perennial residents, surviving the nearly half-year-long dark winter despite their ability to leave. The polar concentrations of disarticulated dinosaur bones were suggested as having resulted from a catastrophic burial of a population by floods. However, this should have fossilized complete skeletons. Alternatively, herds of dinosaurs living in high latitudes might have been sexually driven to spend the half year of continuously illuminated polar summer for mating rather than for nourishment, in which the lower latitudes provided as well. The aggressive mating competitions would have left victims among the rivals and of young ones incidentally trampled over, all being consumed and their skeletons

Embryology of Early Jurassic dinosaur from China with evidence of preserved organic remains.

PubMed

Reisz, Robert R; Huang, Timothy D; Roberts, Eric M; Peng, ShinRung; Sullivan, Corwin; Stein, Koen; LeBlanc, Aaron R H; Shieh, DarBin; Chang, RongSeng; Chiang, ChengCheng; Yang, Chuanwei; Zhong, Shiming

2013-04-11

Fossil dinosaur embryos are surprisingly rare, being almost entirely restricted to Upper Cretaceous strata that record the late stages of non-avian dinosaur evolution. Notable exceptions are the oldest known embryos from the Early Jurassic South African sauropodomorph Massospondylus and Late Jurassic embryos of a theropod from Portugal. The fact that dinosaur embryos are rare and typically enclosed in eggshells limits their availability for tissue and cellular level investigations of development. Consequently, little is known about growth patterns in dinosaur embryos, even though post-hatching ontogeny has been studied in several taxa. Here we report the discovery of an embryonic dinosaur bone bed from the Lower Jurassic of China, the oldest such occurrence in the fossil record. The embryos are similar in geological age to those of Massospondylus and are also assignable to a sauropodomorph dinosaur, probably Lufengosaurus. The preservation of numerous disarticulated skeletal elements and eggshells in this monotaxic bone bed, representing different stages of incubation and therefore derived from different nests, provides opportunities for new investigations of dinosaur embryology in a clade noted for gigantism. For example, comparisons among embryonic femora of different sizes and developmental stages reveal a consistently rapid rate of growth throughout development, possibly indicating that short incubation times were characteristic of sauropodomorphs. In addition, asymmetric radial growth of the femoral shaft and rapid expansion of the fourth trochanter suggest that embryonic muscle activation played an important role in the pre-hatching ontogeny of these dinosaurs. This discovery also provides the oldest evidence of in situ preservation of complex organic remains in a terrestrial vertebrate.

Scaling in Theropod Dinosaurs: Femoral Bone Strength and Locomotion

ERIC Educational Resources Information Center

Lee, Scott

2015-01-01

In our first article on scaling in theropod dinosaurs, the longitudinal stress in the leg bones due to supporting the weight of the animal was studied and found not to control the dimensions of the femur. As a continuation of our study of elasticity in dinosaur bones, we now examine the transverse stress in the femur due to locomotion and find…

Testing co-evolutionary hypotheses over geological timescales: interactions between Mesozoic non-avian dinosaurs and cycads.

PubMed

Butler, Richard J; Barrett, Paul M; Kenrick, Paul; Penn, Malcolm G

2009-02-01

The significance of co-evolution over ecological timescales is well established, yet it remains unclear to what extent co-evolutionary processes contribute to driving large-scale evolutionary and ecological changes over geological timescales. Some of the most intriguing and pervasive long-term co-evolutionary hypotheses relate to proposed interactions between herbivorous non-avian dinosaurs and Mesozoic plants, including cycads. Dinosaurs have been proposed as key dispersers of cycad seeds during the Mesozoic, and temporal variation in cycad diversity and abundance has been linked to dinosaur faunal changes. Here we assess the evidence for proposed hypotheses of trophic and evolutionary interactions between these two groups using diversity analyses, a new database of Cretaceous dinosaur and plant co-occurrence data, and a geographical information system (GIS) as a visualisation tool. Phylogenetic evidence suggests that the origins of several key biological properties of cycads (e.g. toxins, bright-coloured seeds) likely predated the origin of dinosaurs. Direct evidence of dinosaur-cycad interactions is lacking, but evidence from extant ecosystems suggests that dinosaurs may plausibly have acted as seed dispersers for cycads, although it is likely that other vertebrate groups (e.g. birds, early mammals) also played a role. Although the Late Triassic radiations of dinosaurs and cycads appear to have been approximately contemporaneous, few significant changes in dinosaur faunas coincide with the late Early Cretaceous cycad decline. No significant spatiotemporal associations between particular dinosaur groups and cycads can be identified - GIS visualisation reveals disparities between the spatiotemporal distributions of some dinosaur groups (e.g. sauropodomorphs) and cycads that are inconsistent with co-evolutionary hypotheses. The available data provide no unequivocal support for any of the proposed co-evolutionary interactions between cycads and herbivorous dinosaurs

Computational modelling of locomotor muscle moment arms in the basal dinosaur Lesothosaurus diagnosticus: assessing convergence between birds and basal ornithischians.

PubMed

Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M

2012-03-01

Ornithischia (the 'bird-hipped' dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in

Computational modelling of locomotor muscle moment arms in the basal dinosaur Lesothosaurus diagnosticus: assessing convergence between birds and basal ornithischians

PubMed Central

Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M

2012-01-01

Ornithischia (the ‘bird-hipped’ dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in

Establishment of mouse expanded potential stem cells

PubMed Central

Gao, Xuefei; Antunes, Liliana; Yu, Yong; Zhu, Zhexin; Wang, Juexuan; Kolodziejczyk, Aleksandra A.; Campos, Lia S.; Wang, Cui; Yang, Fengtang; Zhong, Zhen; Fu, Beiyuan; Eckersley-Maslin, Melanie A.; Woods, Michael; Tanaka, Yosuke; Chen, Xi; Wilkinson, Adam C.; Bussell, James; White, Jacqui; Ramirez-Solis, Ramiro; Reik, Wolf; Göttgens, Berthold; Teichmann, Sarah A.; Tam, Patrick P. L.; Nakauchi, Hiromitsu; Zou, Xiangang; Lu, Liming; Liu, Pentao

2018-01-01

Mouse embryonic stem cells derived from the epiblast1 contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm2 upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species. PMID:29019987

From dinosaurs to modern bird diversity: extending the time scale of adaptive radiation.

PubMed

Moen, Daniel; Morlon, Hélène

2014-05-01

What explains why some groups of organisms, like birds, are so species rich? And what explains their extraordinary ecological diversity, ranging from large, flightless birds to small migratory species that fly thousand of kilometers every year? These and similar questions have spurred great interest in adaptive radiation, the diversification of ecological traits in a rapidly speciating group of organisms. Although the initial formulation of modern concepts of adaptive radiation arose from consideration of the fossil record, rigorous attempts to identify adaptive radiation in the fossil record are still uncommon. Moreover, most studies of adaptive radiation concern groups that are less than 50 million years old. Thus, it is unclear how important adaptive radiation is over temporal scales that span much larger portions of the history of life. In this issue, Benson et al. test the idea of a "deep-time" adaptive radiation in dinosaurs, compiling and using one of the most comprehensive phylogenetic and body-size datasets for fossils. Using recent phylogenetic statistical methods, they find that in most clades of dinosaurs there is a strong signal of an "early burst" in body-size evolution, a predicted pattern of adaptive radiation in which rapid trait evolution happens early in a group's history and then slows down. They also find that body-size evolution did not slow down in the lineage leading to birds, hinting at why birds survived to the present day and diversified. This paper represents one of the most convincing attempts at understanding deep-time adaptive radiations.

From Dinosaurs to Modern Bird Diversity: Extending the Time Scale of Adaptive Radiation

PubMed Central

Moen, Daniel; Morlon, Hélène

2014-01-01

What explains why some groups of organisms, like birds, are so species rich? And what explains their extraordinary ecological diversity, ranging from large, flightless birds to small migratory species that fly thousand of kilometers every year? These and similar questions have spurred great interest in adaptive radiation, the diversification of ecological traits in a rapidly speciating group of organisms. Although the initial formulation of modern concepts of adaptive radiation arose from consideration of the fossil record, rigorous attempts to identify adaptive radiation in the fossil record are still uncommon. Moreover, most studies of adaptive radiation concern groups that are less than 50 million years old. Thus, it is unclear how important adaptive radiation is over temporal scales that span much larger portions of the history of life. In this issue, Benson et al. test the idea of a “deep-time” adaptive radiation in dinosaurs, compiling and using one of the most comprehensive phylogenetic and body-size datasets for fossils. Using recent phylogenetic statistical methods, they find that in most clades of dinosaurs there is a strong signal of an “early burst” in body-size evolution, a predicted pattern of adaptive radiation in which rapid trait evolution happens early in a group's history and then slows down. They also find that body-size evolution did not slow down in the lineage leading to birds, hinting at why birds survived to the present day and diversified. This paper represents one of the most convincing attempts at understanding deep-time adaptive radiations. PMID:24802950

Epidermal and dermal integumentary structures of ankylosaurian dinosaurs.

PubMed

Arbour, Victoria M; Burns, Michael E; Bell, Phil R; Currie, Philip J

2014-01-01

Ankylosaurian dinosaurs are most notable for their abundant and morphologically diverse osteoderms, which would have given them a spiky appearance in life. Isolated osteoderms are relatively common and provide important information about the structure of the ankylosaur dermis, but fossilized impressions of the soft-tissue epidermis of ankylosaurs are rare. Nevertheless, well-preserved integument exists on several ankylosaur fossils that shows osteoderms were covered by a single epidermal scale, but one or many millimeter-sized ossicles may be present under polygonal, basement epidermal scales. Evidence for the taxonomic utility of ankylosaurid epidermal scale architecture is presented for the first time. This study builds on previous osteological work that argues for a greater diversity of ankylosaurids in the Dinosaur Park Formation of Alberta than has been traditionally recognized and adds to the hypothesis that epidermal skin impressions are taxonomically relevant across diverse dinosaur clades. Copyright © 2013 Wiley Periodicals, Inc.

The Age of Dinosaurs in Russia and Mongolia

NASA Astrophysics Data System (ADS)

Benton, Michael J.; Shishkin, Mikhail A.; Unwin, David M.; Kurochkin, Evgenii N.

2003-12-01

The former Soviet Union covers a vast area of land, and over the last 200 years, many dozens of extraordinary dinosaurs and other fossil amphibians, reptiles, birds and mammals have been found in Mesozoic rocks in its territories. The Permo-Triassic of the Ural Mountains of Russia have produced hundreds of superb specimens, and many of the dinosaurs from Mongolia are unique. This is the first compilation in any Western language of this large body of Russian research and the first time so much of this research, previously unexplored by the West, has been introduced in English. The Age of Dinosaurs in Russia and Mongolia is written by a unique mix of Russian and Western palaeontologists, and provides an entrée to a range of fossil faunas, in particular reptiles, that have been little known outside Russia. It will undoubtedly become a major reference work for all vertebrate palaeontologists.

Lineage-negative Progenitors Mobilize to Regenerate Lung Epithelium after Major Injury

PubMed Central

Vaughan, Andrew E.; Brumwell, Alexis N.; Xi, Ying; Gotts, Jeffrey; Brownfield, Doug G.; Treutlein, Barbara; Tan, Kevin; Tan, Victor; Liu, Fengchun; Looney, Mark R.; Matthay, Michael; Rock, Jason R.; Chapman, Harold A.

2014-01-01

Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ and injury-specific1–4. Current paradigms in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers5–8. In contrast we here define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEPs) cells present within normal distal lung. Quiescent LNEPs activate a ΔNp63/cytokeratin 5 (Krt5+) remodeling program after influenza or bleomycin injury. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, whereupon they differentiate toward mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signaling to activate the ΔNp63/Krt5+ program whereas subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signaling post-injury led to parenchymal micro-honeycombing, indicative of failed regeneration. Lungs from fibrosis patients show analogous honeycomb cysts with evidence of hyperactive Notch signaling. Our findings indicate distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of injury, and the outcomes of regeneration or fibrosis may ride in part on the dynamics of LNEP Notch signaling. PMID:25533958

Prohibitin 2 Regulates the Proliferation and Lineage-Specific Differentiation of Mouse Embryonic Stem Cells in Mitochondria

PubMed Central

Komazaki, Shinji; Enomoto, Kei; Seki, Yasuhiro; Wang, Ying Ying; Ishigaki, Yohei; Ninomiya, Naoto; Noguchi, Taka-aki K.; Kokubu, Yuko; Ohnishi, Keigoh; Nakajima, Yoshiro; Kato, Kaoru; Intoh, Atsushi; Takada, Hitomi; Yamakawa, Norio; Wang, Pi-Chao; Asashima, Makoto; Kurisaki, Akira

2014-01-01

Background The pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown. Methodology/Principal Findings In this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria. Conclusions/Significance Our results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells. PMID:24709813

Resources and energetics determined dinosaur maximal size

PubMed Central

McNab, Brian K.

2009-01-01

Some dinosaurs reached masses that were ≈8 times those of the largest, ecologically equivalent terrestrial mammals. The factors most responsible for setting the maximal body size of vertebrates are resource quality and quantity, as modified by the mobility of the consumer, and the vertebrate's rate of energy expenditure. If the food intake of the largest herbivorous mammals defines the maximal rate at which plant resources can be consumed in terrestrial environments and if that limit applied to dinosaurs, then the large size of sauropods occurred because they expended energy in the field at rates extrapolated from those of varanid lizards, which are ≈22% of the rates in mammals and 3.6 times the rates of other lizards of equal size. Of 2 species having the same energy income, the species that uses the most energy for mass-independent maintenance of necessity has a smaller size. The larger mass found in some marine mammals reflects a greater resource abundance in marine environments. The presumptively low energy expenditures of dinosaurs potentially permitted Mesozoic communities to support dinosaur biomasses that were up to 5 times those found in mammalian herbivores in Africa today. The maximal size of predatory theropods was ≈8 tons, which if it reflected the maximal capacity to consume vertebrates in terrestrial environments, corresponds in predatory mammals to a maximal mass less than a ton, which is what is observed. Some coelurosaurs may have evolved endothermy in association with the evolution of feathered insulation and a small mass. PMID:19581600

Resources and energetics determined dinosaur maximal size.

PubMed

McNab, Brian K

2009-07-21

Some dinosaurs reached masses that were approximately 8 times those of the largest, ecologically equivalent terrestrial mammals. The factors most responsible for setting the maximal body size of vertebrates are resource quality and quantity, as modified by the mobility of the consumer, and the vertebrate's rate of energy expenditure. If the food intake of the largest herbivorous mammals defines the maximal rate at which plant resources can be consumed in terrestrial environments and if that limit applied to dinosaurs, then the large size of sauropods occurred because they expended energy in the field at rates extrapolated from those of varanid lizards, which are approximately 22% of the rates in mammals and 3.6 times the rates of other lizards of equal size. Of 2 species having the same energy income, the species that uses the most energy for mass-independent maintenance of necessity has a smaller size. The larger mass found in some marine mammals reflects a greater resource abundance in marine environments. The presumptively low energy expenditures of dinosaurs potentially permitted Mesozoic communities to support dinosaur biomasses that were up to 5 times those found in mammalian herbivores in Africa today. The maximal size of predatory theropods was approximately 8 tons, which if it reflected the maximal capacity to consume vertebrates in terrestrial environments, corresponds in predatory mammals to a maximal mass less than a ton, which is what is observed. Some coelurosaurs may have evolved endothermy in association with the evolution of feathered insulation and a small mass.

Mapping Metal Elements of Shuangbai Dinosaur Fossil by Synchrotron X-ray Fluorescence Microprobe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Y.; Qun, Y; Ablett, J

The metal elements mapping of Shuangbai dinosaur fossil, was obtained by synchrotron x-ray fluorescence (SXRF). Eight elements, Ca, Mn, Fe, Cu, Zn, As, Y and Sr were determined. Elements As and Y were detected for the first time in the dinosaur fossil. The data indicated that metal elements are asymmetrical on fossil section. This is different from common minerals. Mapping metals showed that metal element As is few. The dinosaur most likely belongs to natural death. This is different from Zigong dinosaurs which were found dead from poisoning. This method has been used to find that metals Fe and Mnmore » are accrete, and the same is true for Sr and Y. This study indicated that colloid granule Fe and Mn, as well as Sr and Y had opposite electric charges in lithification process of fossils. By this analysis, compound forms can be ascertained. Synchrotron light source x-ray fluorescence is a complementary method that shows mapping of metal elements at the dinosaur fossil, and is rapid, exact and intuitionist. This study shows that dinosaur fossil mineral imaging has a potential in reconstructing the paleoenvironment and ancient geology.« less

Analysis of dinosaur samples by nuclear microscopy

NASA Astrophysics Data System (ADS)

Wu, Xiankang; Orlić, I.; Tang, S. M.; Wang, Yiming; Wang, Xiaohong; Zhu, Jieqing

1997-07-01

Several dinosaur bone and eggshell fossil samples unearthed at different sites in China were analyzed by means of nuclear microscopy. Concentrations and distributions of elements such as Na, Mg, Al, P, S, Ca, Cr, Mn, Fe, Cu, Zn, As, Br, Sr, Y, Ce, Pb and U, etc. were obtained for each sample. The results of quantitative PIXE and RBS analyses show unusually high concentrations of U and Ce in several samples obtained from a period near the K-T boundary (between Cretaceous and Tertiary periods, 65 million years ago), suggesting that some form of environmental pollution could be the cause of dinosaur extinction.

Scaling in Theropod Dinosaurs: Femoral Bone Dimensions

NASA Astrophysics Data System (ADS)

Lee, Scott A.

2014-05-01

Finding topics that inspire students is an important aspect of any physics course. Virtually everyone is fascinated by Tyrannosaurus rex, and the excitement of the class is palpable when we explore scaling effects in T. rex and other bipedal theropod dinosaurs as part of our discussion of mechanics and elasticity. In this paper, we explore the role of longitudinal stress in the femur bones due to the weight of the dinosaur in determining how the geometry of the femur changes with size of the theropod. This is one area of allometry the study of how different biological characteristics scale with size.

Neural stem cells induce the formation of their physical niche during organogenesis

PubMed Central

Riebesehl, Bea F; Ambrosio, Elizabeth M; Stolper, Julian S; Lischik, Colin Q; Dross, Nicolas

2017-01-01

Most organs rely on stem cells to maintain homeostasis during post-embryonic life. Typically, stem cells of independent lineages work coordinately within mature organs to ensure proper ratios of cell types. Little is known, however, on how these different stem cells locate to forming organs during development. Here we show that neuromasts of the posterior lateral line in medaka are composed of two independent life-long lineages with different embryonic origins. Clonal analysis and 4D imaging revealed a hierarchical organisation with instructing and responding roles: an inner, neural lineage induces the formation of an outer, border cell lineage (nBC) from the skin epithelium. Our results demonstrate that the neural lineage is necessary and sufficient to generate nBCs highlighting self-organisation principles at the level of the entire embryo. We hypothesise that induction of surrounding tissues plays a major role during the establishment of vertebrate stem cell niches. PMID:28950935

Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

PubMed Central

Feng, Lijuan; Shi, Zhen; Chen, Xin

2017-01-01

Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

Cell Lineage Analysis of the Mammalian Female Germline

PubMed Central

Elbaz, Judith; Jinich, Adrian; Chapal-Ilani, Noa; Maruvka, Yosef E.; Nevo, Nava; Marx, Zipora; Horovitz, Inna; Wasserstrom, Adam; Mayo, Avi; Shur, Irena; Benayahu, Dafna; Skorecki, Karl; Segal, Eran; Dekel, Nava; Shapiro, Ehud

2012-01-01

Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote). We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development. PMID:22383887

Ontogeny and the fossil record: what, if anything, is an adult dinosaur?

PubMed

Hone, David W E; Farke, Andrew A; Wedel, Mathew J

2016-02-01

Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an 'adult' animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered 'adults' in a modern-day field study are considered 'juveniles' or 'subadults' in palaeontological contexts. © 2016 The Author(s).

Ontogeny and the fossil record: what, if anything, is an adult dinosaur?

PubMed Central

2016-01-01

Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an ‘adult’ animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered ‘adults’ in a modern-day field study are considered ‘juveniles’ or ‘subadults’ in palaeontological contexts. PMID:26888916

Scaling in Theropod Dinosaurs: Femoral Bone Strength and Locomotion II

ERIC Educational Resources Information Center

Lee, Scott

2015-01-01

In the second paper of this series, the effect of transverse femoral stresses due to locomotion in theropod dinosaurs of different sizes was examined for the case of an unchanging leg geometry. Students are invariably thrilled to learn about theropod dinosaurs, and this activity applies the concepts of torque and stress to the issue of theropod…

Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes

PubMed Central

Liu, Qiaozhen; Yang, Rui; Huang, Xiuzhen; Zhang, Hui; He, Lingjuan; Zhang, Libo; Tian, Xueying; Nie, Yu; Hu, Shengshou; Yan, Yan; Zhang, Li; Qiao, Zengyong; Wang, Qing-Dong; Lui, Kathy O; Zhou, Bin

2016-01-01

Cardiac cells marked by c-Kit or Kit, dubbed cardiac stem cells (CSCs), are in clinical trials to investigate their ability to stimulate cardiac regeneration and repair. These studies were initially motivated by the purported cardiogenic activity of these cells. Recent lineage tracing studies using Kit promoter to drive expression of the inducible Cre recombinase showed that these CSCs had highly limited cardiogenic activity, inadequate to support efficient cardiac repair. Here we reassess the lineage tracing data by investigating the identity of cells immediately after Cre labeling. Our instant lineage tracing approach identifies Kit-expressing cardiomyocytes, which are labeled immediately after tamoxifen induction. In combination with long-term lineage tracing experiments, these data reveal that the large majority of long-term labeled cardiomyocytes are pre-existing Kit-expressing cardiomyocytes rather than cardiomyocytes formed de novo from CSCs. This study presents a new interpretation for the contribution of Kit+ cells to cardiomyocytes and shows that Kit genetic lineage tracing over-estimates the cardiogenic activity of Kit+ CSCs. PMID:26634606

Loss of Anterior Gradient 2 (Agr2) Expression Results in Hyperplasia and Defective Lineage Maturation in the Murine Stomach*

PubMed Central

Gupta, Aparna; Wodziak, Dariusz; Tun, May; Bouley, Donna M.; Lowe, Anson W.

2013-01-01

Recent studies of epithelial tissues have revealed the presence of tissue-specific stem cells that are able to establish multiple cell lineages within an organ. The stem cells give rise to progenitors that replicate before differentiating into specific cell lineages. The mechanism by which homeostasis is established between proliferating stem or progenitor cells and terminally differentiated cells is unclear. This study demonstrates that Agr2 expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while also inhibiting the proliferation of stem or progenitor cells. When Agr2 expression is absent, gastric mucous neck cells increased in number as does the number of proliferating cells. Agr2 expression loss also resulted in the decline of terminally differentiated cells, which was supplanted by cells that exhibited nuclear SOX9 labeling. Sox9 expression has been associated with progenitor and stem cells. Similar effects of the Agr2 null on cell proliferation in the intestine were also observed. Agr2 consequently serves to maintain the balance between proliferating and differentiated epithelial cells. PMID:23209296

High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vega, Sebastián L.; Liu, Er; Arvind, Varun

Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regionsmore » of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative “imaging-derived” parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. - Highlights: • High-content analysis of nuclear shape and organization classify stem and progenitor cells poised for distinct lineages. • Early oncogenic changes in mesenchymal stem cells (MSCs) are also detected with nuclear descriptors. • A new class of cancer-mitigating biomaterials was identified based on

Molecular analyses of dinosaur osteocytes support the presence of endogenous molecules.

PubMed

Schweitzer, Mary Higby; Zheng, Wenxia; Cleland, Timothy P; Bern, Marshall

2013-01-01

The discovery of soft, transparent microstructures in dinosaur bone consistent in morphology with osteocytes was controversial. We hypothesize that, if original, these microstructures will have molecular features in common with extant osteocytes. We present immunological and mass spectrometry evidence for preservation of proteins comprising extant osteocytes (Actin, Tubulin, PHEX, Histone H4) in osteocytes recovered from two non-avian dinosaurs. Furthermore, antibodies to DNA show localized binding to these microstructures, which also react positively with DNA intercalating stains propidium iodide (PI) and 4',6'-diamidino-2-phenylindole dihydrochloride (DAPI). Each antibody binds dinosaur cells in patterns similar to extant cells. These data are the first to support preservation of multiple proteins and to present multiple lines of evidence for material consistent with DNA in dinosaurs, supporting the hypothesis that these structures were part of the once living animals. We propose mechanisms for preservation of cells and component molecules, and discuss implications for dinosaurian cellular biology. Copyright © 2012 Elsevier Inc. All rights reserved.

Deep faunistic turnovers preceded the rise of dinosaurs in southwestern Pangaea.

PubMed

Ezcurra, Martín D; Fiorelli, Lucas E; Martinelli, Agustín G; Rocher, Sebastián; von Baczko, M Belén; Ezpeleta, Miguel; Taborda, Jeremías R A; Hechenleitner, E Martín; Trotteyn, M Jimena; Desojo, Julia B

2017-10-01

The Triassic period documents the origin and diversification of modern amniote lineages and the Late Triassic fossil record of South America has been crucial to shed light on these early evolutionary histories. However, the faunistic changes that led to the establishment of Late Triassic ecosystems are largely ignored because of the global scarcity of fossils from assemblages a few million years older. Here we contribute to fill this gap with the description of a new tetrapod assemblage from the lowermost levels of the Chañares Formation (uppermost Middle-lower Late Triassic epochs) of Argentina, which is older than the other vertebrate assemblages of the same basin. The new assemblage is composed of therapsids, rhynchosaurids and archosaurs, and clearly differs from that of the immediately overlying and well-known historical Chañares vertebrate assemblage. The new tetrapod association is part of a phase of relatively rapidly changing vertebrate assemblage compositions, in a time span shorter than 6 million years, before the diversification of dinosaurs and other common Late Triassic tetrapods in southwestern Pangaea.

A lineage CLOUD for neoblasts.

PubMed

Tran, Thao Anh; Gentile, Luca

2018-05-10

In planarians, pluripotency can be studied in vivo in the adult animal, making these animals a unique model system where pluripotency-based regeneration (PBR)-and its therapeutic potential-can be investigated. This review focuses on recent findings to build a cloud model of fate restriction likelihood for planarian stem and progenitor cells. Recently, a computational approach based on functional and molecular profiling at the single cell level was proposed for human hematopoietic stem cells. Based on data generated both in vivo and ex vivo, we hypothesized that planarian stem cells could acquire multiple direction lineage biases, following a "badlands" landscape. Instead of a discrete tree-like hierarchy, where the potency of stem/progenitor cells reduces stepwise, we propose a Continuum of LOw-primed UnDifferentiated Planarian Stem/Progenitor Cells (CLOUD-PSPCs). Every subclass of neoblast/progenitor cells is a cloud of likelihood, as the single cell transcriptomics data indicate. The CLOUD-HSPCs concept was substantiated by in vitro data from cell culture; therefore, to confirm the CLOUD-PSPCs model, the planarian community needs to develop new tools, like live cell tracking. Future studies will allow a deeper understanding of PBR in planarian, and the possible implications for regenerative therapies in human. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adaptive and Pathogenic Responses to Stress by Stem Cells during Development.

PubMed

Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

2012-12-10

Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

PubMed Central

Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

2012-01-01

Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies. PMID:24710551

Haemopoietic stem cells.

PubMed

Bellantuono, Ilaria

2004-04-01

Considerable effort has been made in recent years in understanding the mechanisms that govern stem cell generation, proliferation, self-renewal, commitment and lately plasticity. In the development of the haemopoietic system during embryonic and fetal life the notion of different pools of stem cells arising from the endothelium is gaining consensus. Gene expression profiling of populations of stem cells is bringing to light categories of genes important for self-renewal or commitment. Besides the role of transcription factors in lineage decision, the role of soluble factors and transmembrane proteins, very active at the time of embryo development, are taking central stage in the maintenance and in vitro expansion of haemopoietic stem cells (HSCs). The hierarchical model of haemopoietic development is being questioned with reports of lineage switching and plasticity of haemopoietic stem cells to non-haemopoietic cells. Yet the understanding of the overall process is still very fragmented and hypothetical. This is mainly due to the absence of appropriate markers to enable selection of homogeneous stem cell populations and the need to rely on retrospective functional assays, able only to determine the overall behaviour of a population of cells. This review is intended to be an overview of the haemopoietic system and a critical re-visitation of issues such as plasticity and self-renewal important for therapeutic applications of haemopoietic stem cells.

CRETACEOUS CLIMATE SENSITIVITY STUDY USING DINOSAUR & PLANT PALEOBIOGEOGRAPHY

NASA Astrophysics Data System (ADS)

Goswami, A.; Main, D. J.; Noto, C. R.; Moore, T. L.; Scotese, C.

2009-12-01

The Early Cretaceous was characterized by cool poles and moderate global temperatures (~16° C). During the mid and late Cretaceous, long-term global warming (~20° - 22° C) was driven by increasing levels of CO2, rising sea level (lowering albedo) and the continuing breakup of Pangea. Paleoclimatic reconstructions for four time intervals during the Cretaceous: Middle Campanian (80 Ma), Cenomanian/Turonian (90 Ma), Early Albian (110 Ma) and Barremian-Hauterivian (130Ma) are presented here. These paleoclimate simulations were prepared using the Fast Ocean and Atmosphere Model (FOAM). The simulated results show the pattern of the pole-to-Equator temperature gradients, rainfall, surface run-off, the location of major rivers and deltas. In order to investigate the effect of potential dispersal routes on paleobiogeographic patterns, a time-slice series of maps from Early - Late Cretaceous were produced showing plots of dinosaur and plant fossil distributions. These Maps were created utilizing: 1) plant fossil localities from the GEON and Paleobiology (PBDB) databases; and 2) dinosaur fossil localities from an updated version of the Dinosauria (Weishampel, 2004) database. These results are compared to two different types of datasets, 1) Paleotemperature database for the Cretaceous and 2) locality data obtained from GEON, PBDB and Dinosauria database. Global latitudinal mean temperatures from both the model and the paelotemperature database were plotted on a series of latitudinal graphs along with the distributions of fossil plants and dinosaurs. It was found that most dinosaur localities through the Cretaceous tend to cluster within specific climate belts, or envelopes. Also, these Cretaceous maps show variance in biogeographic zonation of both plants and dinosaurs that is commensurate with reconstructed climate patterns and geography. These data are particularly useful for understanding the response of late Mesozoic ecosystems to geographic and climatic conditions that

Ecological interactions in dinosaur communities: influences of small offspring and complex ontogenetic life histories.

PubMed

Codron, Daryl; Carbone, Chris; Clauss, Marcus

2013-01-01

Because egg-laying meant that even the largest dinosaurs gave birth to very small offspring, they had to pass through multiple ontogenetic life stages to adulthood. Dinosaurs' successors as the dominant terrestrial vertebrate life form, the mammals, give birth to live young, and have much larger offspring and less complex ontogenetic histories. The larger number of juveniles in dinosaur as compared to mammal ecosystems represents both a greater diversity of food available to predators, and competitors for similar-sized individuals of sympatric species. Models of population abundances across different-sized species of dinosaurs and mammals, based on simulated ecological life tables, are employed to investigate how differences in predation and competition pressure influenced dinosaur communities. Higher small- to medium-sized prey availability leads to a normal body mass-species richness (M-S) distribution of carnivorous dinosaurs (as found in the theropod fossil record), in contrast to the right-skewed M-S distribution of carnivorous mammals (as found living members of the order Carnivora). Higher levels of interspecific competition leads to a left-skewed M-S distribution in herbivorous dinosaurs (as found in sauropods and ornithopods), in contrast to the normal M-S distribution of large herbivorous mammals. Thus, our models suggest that differences in reproductive strategy, and consequently ontogeny, explain observed differences in community structure between dinosaur and mammal faunas. Models also show that the largest dinosaurian predators could have subsisted on similar-sized prey by including younger life stages of the largest herbivore species, but that large predators likely avoided prey much smaller than themselves because, despite predicted higher abundances of smaller than larger-bodied prey, contributions of small prey to biomass intake would be insufficient to satisfy meat requirements. A lack of large carnivores feeding on small prey exists in mammals

Lineage mapping and characterization of the native progenitor population in cellular allograft.

PubMed

Neman, Josh; Duenas, Vincent; Kowolik, Claudia; Hambrecht, Amanda; Chen, Mike; Jandial, Rahul

2013-02-01

The gold standard for bone grafting remains the autograft. However, the attractiveness of autograft is counterbalanced by donor site morbidity. To mimic autograft-and its fundamental properties of osteoconductivity, osteoinductivity, and osteogenicity-novel bone grafting materials such as cellular allograft (Osteocel Plus) are composed of allograft in which the progenitor cells are preserved. However, the true identity of these cells remains obscure largely due to the lack of specific bona fide antigenic markers for stem versus progenitor cells. To characterize the stem and progenitor population in cellular allograft, Osteocel Plus. To determine whether cells endogenous to a cellular allograft undergo extensive self-renewal (a functional hallmark of stem cells), we employed a novel use of lineage mapping using a modern and refined replication incompetent lentiviral library with high complexity to uniquely label single cells with indelible genetic tags faithfully passed on to all progeny, allowing identification of highly proliferative clones. We used genetic and proteomic profiling as well as functional assays to show that these cells are capable of multipotential differentiation (the second functional hallmark of stem cells). Use of these two functional hallmarks enabled us to establish the existence of a stem and progenitor cell population in cellular allografts. Specifically, we employed (1) cellular dissociation and (2) in vitro expansion and differentiation capacity of cells released from cellular allograft. We determined differential gene expression profiling of a bona fide human mesenchymal stem cell line and cells from cellular allograft using focused PCR arrays mesenchymal stem cell (MSC) and osteogenesis associated. Proteomic profiling of cells from cellular allograft was performed using (1) immunofluorescence for BMP-2, Runx2 SMADs, CD44, Stro-1, Collagen, RANKL, Osterix Osteocalcin, and Ki67; (2) flow cytometry for Ki67, CD44, Stro-1, Thy1, CD146, and

DinoViz: Exploring the History and Nature of Science through the Progression of Dinosaur Visualization

ERIC Educational Resources Information Center

Clary, Renee; Wandersee, James

2011-01-01

Dinosaurs in the middle school classroom can be exciting. These extinct reptiles are both an exotic subject and familiar to our students. Because students are inherently interested, dinosaurs can serve as an effective portal for the integration of biology, geology, ecology, and the history and nature of science. The field of dinosaur study is…

Intestinal stem cells and their defining niche.

PubMed

Tan, David Wei-Min; Barker, Nick

2014-01-01

The intestinal epithelium is a classic example of a rapidly self-renewing tissue fueled by dedicated resident stem cells. These stem cells reside at the crypt base, generating committed progeny that mature into the various functional epithelial lineages while following a rapid migratory path toward the villi. Two models of intestinal stem cell location were proposed half a century ago and data have been presented in support of both models, dividing the scientific community. Molecular markers have been identified and validated using new techniques such as in vivo lineage tracing and ex vivo organoid culture. The intestinal stem cell niche comprises both epithelial cells, in particular the Paneth cell, and the stromal compartment, where cell-associated ligands and soluble factors regulate stem cell behavior. This review highlights the recent advances in identifying and characterizing the intestinal stem cells and their defining niche. © 2014 Elsevier Inc. All rights reserved.

Blastema cells derived from New Zealand white rabbit's pinna carry stemness properties as shown by differentiation into insulin producing, neural, and osteogenic lineages representing three embryonic germ layers.

PubMed

Saeinasab, Morvarid; Matin, Maryam M; Rassouli, Fatemeh B; Bahrami, Ahmad Reza

2016-05-01

Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capacities. Regeneration is a phenomenon that occurs in a limited number of animals after injury, during which blastema tissue is formed. It has been hypothesized that upon injury, the dedifferentiation of surrounding tissues leads into the appearance of cells with SC characteristics. In present study, stem-like cells (SLCs) were obtained from regenerating tissue of New Zealand white rabbit's pinna and their stemness properties were examined by their capacity to differentiate toward insulin producing cells (IPCs), as well as neural and osteogenic lineages. Differentiation was induced by culture of SLCs in defined medium, and cell fates were monitored by specific staining, RT-PCR and flow cytometry assays. Our results revealed that dithizone positive cells, which represent IPCs, and islet-like structures appeared 1 week after induction of SLCs, and this observation was confirmed by the elevated expression of Ins, Pax6 and Glut4 at mRNA level. Furthermore, SLCs were able to express neural markers as early as 1 week after retinoic acid treatment. Finally, SLCs were able to differentiate into osteogenic lineage, as confirmed by Alizarin Red S staining and RT-PCR studies. In conclusion, SLCs, which could successfully differentiate into cells derived from all three germ layers, can be considered as a valuable model to study developmental biology and regenerative medicine.

How has our knowledge of dinosaur diversity through geologic time changed through research history?

PubMed Central

2018-01-01

Assessments of dinosaur macroevolution at any given time can be biased by the historical publication record. Recent studies have analysed patterns in dinosaur diversity that are based on secular variations in the numbers of published taxa. Many of these have employed a range of approaches that account for changes in the shape of the taxonomic abundance curve, which are largely dependent on databases compiled from the primary published literature. However, how these ‘corrected’ diversity patterns are influenced by the history of publication remains largely unknown. Here, we investigate the influence of publication history between 1991 and 2015 on our understanding of dinosaur evolution using raw diversity estimates and shareholder quorum subsampling for the three major subgroups: Ornithischia, Sauropodomorpha, and Theropoda. We find that, while sampling generally improves through time, there remain periods and regions in dinosaur evolutionary history where diversity estimates are highly volatile (e.g. the latest Jurassic of Europe, the mid-Cretaceous of North America, and the Late Cretaceous of South America). Our results show that historical changes in database compilation can often substantially influence our interpretations of dinosaur diversity. ‘Global’ estimates of diversity based on the fossil record are often also based on incomplete, and distinct regional signals, each subject to their own sampling history. Changes in the record of taxon abundance distribution, either through discovery of new taxa or addition of existing taxa to improve sampling evenness, are important in improving the reliability of our interpretations of dinosaur diversity. Furthermore, the number of occurrences and newly identified dinosaurs is still rapidly increasing through time, suggesting that it is entirely possible for much of what we know about dinosaurs at the present to change within the next 20 years. PMID:29479504

How has our knowledge of dinosaur diversity through geologic time changed through research history?

PubMed

Tennant, Jonathan P; Chiarenza, Alfio Alessandro; Baron, Matthew

2018-01-01

Assessments of dinosaur macroevolution at any given time can be biased by the historical publication record. Recent studies have analysed patterns in dinosaur diversity that are based on secular variations in the numbers of published taxa. Many of these have employed a range of approaches that account for changes in the shape of the taxonomic abundance curve, which are largely dependent on databases compiled from the primary published literature. However, how these 'corrected' diversity patterns are influenced by the history of publication remains largely unknown. Here, we investigate the influence of publication history between 1991 and 2015 on our understanding of dinosaur evolution using raw diversity estimates and shareholder quorum subsampling for the three major subgroups: Ornithischia, Sauropodomorpha, and Theropoda. We find that, while sampling generally improves through time, there remain periods and regions in dinosaur evolutionary history where diversity estimates are highly volatile (e.g. the latest Jurassic of Europe, the mid-Cretaceous of North America, and the Late Cretaceous of South America). Our results show that historical changes in database compilation can often substantially influence our interpretations of dinosaur diversity. 'Global' estimates of diversity based on the fossil record are often also based on incomplete, and distinct regional signals, each subject to their own sampling history. Changes in the record of taxon abundance distribution, either through discovery of new taxa or addition of existing taxa to improve sampling evenness, are important in improving the reliability of our interpretations of dinosaur diversity. Furthermore, the number of occurrences and newly identified dinosaurs is still rapidly increasing through time, suggesting that it is entirely possible for much of what we know about dinosaurs at the present to change within the next 20 years.

Evidence of two distinct functionally specialized fibroblast lineages in breast stroma.

PubMed

Morsing, Mikkel; Klitgaard, Marie Christine; Jafari, Abbas; Villadsen, René; Kassem, Moustapha; Petersen, Ole William; Rønnov-Jessen, Lone

2016-11-03

The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. The two lineages are prospectively isolated by fluorescence activated cell sorting (FACS) based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271 low /MUC1 high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase-stained cultures. Lobular fibroblasts are CD105 high /CD26 low while interlobular fibroblasts are CD105 low /CD26 high . Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that

Molecular preservation in Late Cretaceous sauropod dinosaur eggshells.

PubMed

Schweitzer, M H; Chiappe, L; Garrido, A C; Lowenstein, J M; Pincus, S H

2005-04-22

Exceptionally preserved sauropod eggshells discovered in Upper Cretaceous (Campanian) deposits in Patagonia, Argentina, contain skeletal remains and soft tissues of embryonic Titanosaurid dinosaurs. To preserve these labile embryonic remains, the rate of mineral precipitation must have superseded post-mortem degradative processes, resulting in virtually instantaneous mineralization of soft tissues. If so, mineralization may also have been rapid enough to retain fragments of original biomolecules in these specimens. To investigate preservation of biomolecular compounds in these well-preserved sauropod dinosaur eggshells, we applied multiple analytical techniques. Results demonstrate organic compounds and antigenic structures similar to those found in extant eggshells.

Molecular preservation in Late Cretaceous sauropod dinosaur eggshells

PubMed Central

Schweitzer, M.H; Chiappe, L; Garrido, A.C; Lowenstein, J.M; Pincus, S.H

2005-01-01

Exceptionally preserved sauropod eggshells discovered in Upper Cretaceous (Campanian) deposits in Patagonia, Argentina, contain skeletal remains and soft tissues of embryonic Titanosaurid dinosaurs. To preserve these labile embryonic remains, the rate of mineral precipitation must have superseded post-mortem degradative processes, resulting in virtually instantaneous mineralization of soft tissues. If so, mineralization may also have been rapid enough to retain fragments of original biomolecules in these specimens. To investigate preservation of biomolecular compounds in these well-preserved sauropod dinosaur eggshells, we applied multiple analytical techniques. Results demonstrate organic compounds and antigenic structures similar to those found in extant eggshells. PMID:15888409

Scaling in Theropod Dinosaurs: Femoral Bone Strength and Locomotion

NASA Astrophysics Data System (ADS)

Lee, Scott

2015-02-01

In our first article1 on scaling in theropod dinosaurs, the longitudinal stress in the leg bones due to supporting the weight of the animal was studied and found not to control the dimensions of the femur. As a continuation of our study of elasticity in dinosaur bones, we now examine the transverse stress in the femur due to locomotion and find that this effect is important for the geometry of the bone. We find that larger theropods (including Tyrannosaurus rex) were less athletic than smaller theropods.

Dental histology of Coelophysis bauri and the evolution of tooth attachment tissues in early dinosaurs.

PubMed

Fong, Raymond K M; LeBlanc, Aaron R H; Berman, David S; Reisz, Robert R

2016-07-01

Studies of dinosaur teeth have focused primarily on external crown morphology and thus, use shed or in situ tooth crowns, and are limited to the enamel and dentine dental tissues. As a result, the full suites of periodontal tissues that attach teeth to the jaws remain poorly documented, particularly in early dinosaurs. These tissues are an integral part of the tooth and thus essential to a more complete understanding of dental anatomy, development, and evolution in dinosaurs. To identify the tooth attachment tissues in early dinosaurs, histological thin sections were prepared from the maxilla and dentary of a partial skull of the early theropod Coelophysis bauri from the Upper Triassic (Rhaetian- 209-201 Ma) Whitaker Quarry, New Mexico, USA. As one of the phylogenetically and geologically oldest dinosaurs, it is an ideal candidate for examining dental tissues near the base of the dinosaurian clade. The teeth of C. bauri exhibited a fibrous tooth attachment in which the teeth possessed five tissues: enamel, dentine, cementum, periodontal ligament (PDL), and alveolar bone. Our findings, coupled with those of more recent studies of ornithischian teeth, indicate that a tripartite periodontium, similar to that of crocodilians and mammals, is the plesiomorphic condition for dinosaurs. The occurrence of a tripartite periodontium in dinosaurs adds to the growing consensus that the presence of these tissues is the plesiomorphic condition for the major amniote clades. Furthermore, this study establishes the relative timing of tissue development and growth directions of periodontal tissues and provides the first comparative framework for future studies of dinosaur periodontal development, tooth replacement, and histology. J. Morphol. 277:916-924, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone.

PubMed

Tolkachov, Alexander; Fischer, Cornelius; Ambrosi, Thomas H; Bothe, Melissa; Han, Chung-Ting; Muenzner, Matthias; Mathia, Susanne; Salminen, Marjo; Seifert, Georg; Thiele, Mario; Duda, Georg N; Meijsing, Sebastiaan H; Sauer, Sascha; Schulz, Tim J; Schupp, Michael

2018-03-26

The transcription factor GATA2 is required for expansion and differentiation of hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs) GATA2 blocks adipogenesis, but its biological relevance and underlying genomic events are unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs binds near genes involved in skeletal system development and co-localizes with motifs for FOX and HOX transcription factors, known regulators of skeletal development. Ectopic GATA2 blocks osteoblastogenesis by interfering with SMAD1/5/8 activation. MSC-specific deletion of GATA2 in mice increases numbers and differentiation capacity of bone-derived precursors, resulting in elevated bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs trabecularization and mechanical strength of bone, involving reduced MSC expression of the osteoclast inhibitor osteoprotegerin and increased osteoclast numbers. Thus, GATA2 affects bone turnover via MSC-autonomous and indirect effects. By regulating bone trabecularization, GATA2 expression in the osteogenic lineage may contribute to the anatomical and cellular microenvironment of the HSC niche required for hematopoiesis. Copyright © 2018 American Society for Microbiology.

Unexpected amino acid composition of modern Reptilia and its implications in molecular mechanisms of dinosaur extinction.

PubMed

Wang, Guang-Zhong; Ma, Bin-Guang; Yang, Yan; Zhang, Hong-Yu

2005-08-12

Dinosaur extinction is a great challenge to evolutionary biology. Although accumulating evidence suggests that an abrupt change of environment, such as a long period of low temperature induced by asteroid hit or other disasters, may be responsible for dinosaur extinction, little is known about the underlying molecular mechanisms. By analyzing the amino acid compositions of 13 biological classes, we found that the charged amino acid content of modern Reptilia, the sibling of dinosaur, is strikingly different from those of other classes, which inspires us to propose a possible molecular mechanism for dinosaur extinction.

Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

DTIC Science & Technology

2012-07-01

Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

Osteoblastic/Cementoblastic and Neural Differentiation of Dental Stem Cells and Their Applications to Tissue Engineering and Regenerative Medicine

PubMed Central

Kim, Byung-Chul; Bae, Hojae; Kwon, Il-Keun; Lee, Eun-Jun; Park, Jae-Hong

2012-01-01

Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine. PMID:22224548

Osteoblastic/cementoblastic and neural differentiation of dental stem cells and their applications to tissue engineering and regenerative medicine.

PubMed

Kim, Byung-Chul; Bae, Hojae; Kwon, Il-Keun; Lee, Eun-Jun; Park, Jae-Hong; Khademhosseini, Ali; Hwang, Yu-Shik

2012-06-01

Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine.

Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells.

PubMed

Nosi, Ursula; Lanner, Fredrik; Huang, Tsu; Cox, Brian

2017-05-09

The first cell fate choice of the preimplantation embryo generates the extraembryonic trophoblast and embryonic epiblast lineages. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) can be utilized to investigate molecular mechanisms of this first cell fate decision. It has been established that ESCs can be induced to acquire trophoblast lineage characteristics upon manipulation of lineage-determining transcription factors. Here, we have interrogated the potential of microRNAs (miRNAs) to drive trans-differentiation of ESCs into the trophoblast lineage. Analysis of gene expression data identified a network of TSC-enriched miRNAs that were predicted to target mRNAs enriched in ESCs. Ectopic expression of these miRNAs in ESCs resulted in a stable trophoblast phenotype, supported by gene expression changes and in vivo contribution potential. This process is highly miRNA-specific and dependent on Hdac2 inhibition. Our experimental evidence suggests that these miRNAs promote a mural trophectoderm (TE)-like cell fate with physiological properties that differentiate them from the polar TE. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Bringing dinosaurs back to life: exhibiting prehistory at the American Museum of Natural History.

PubMed

Rieppel, Lukas

2012-09-01

This essay examines the exhibition of dinosaurs at the American Museum of Natural History during the first two decades of the twentieth century. Dinosaurs provide an especially illuminating lens through which to view the history of museum display practices for two reasons: they made for remarkably spectacular exhibits; and they rested on contested theories about the anatomy, life history, and behavior of long-extinct animals to which curators had no direct observational access. The American Museum sought to capitalize on the popularity of dinosaurs while mitigating the risks of mounting an overtly speculative display by fashioning them into a kind of mixed-media installation made of several elements, including fossilized bone, shellac, iron, and plaster. The resulting sculptures provided visitors with a vivid and lifelike imaginative experience. At the same time, curators, who were anxious to downplay the speculative nature of mounted dinosaurs, drew systematic attention to the material connection that tied individual pieces of fossilized bone to the actual past. Freestanding dinosaurs can therefore be read to have functioned as iconic sculptures that self-consciously advertised their indexical content.

Dietary adaptions in the ultrastructure of dinosaur dentine.

PubMed

Brink, Kirstin S; Chen, Yu-Cheng; Wu, Ya-Na; Liu, Wei-Min; Shieh, Dar-Bin; Huang, Timothy D; Sun, Chi-Kuang; Reisz, Robert R

2016-12-01

Teeth are key to understanding the feeding ecology of both extant and extinct vertebrates. Recent studies have highlighted the previously unrecognized complexity of dinosaur dentitions and how specific tooth tissues and tooth shapes differ between taxa with different diets. However, it is unknown how the ultrastructure of these tooth tissues contributes to the differences in feeding style between taxa. In this study, we use third harmonic generation microscopy and scanning electron microscopy to examine the ultrastructure of the dentine in herbivorous and carnivorous dinosaurs to understand how the structure of this tissue contributes to the overall utility of the tooth. Morphometric analyses of dentinal tubule diameter, density and branching rates reveal a strong signal for dietary preferences, with herbivorous saurischian and ornithischian dinosaurs consistently having higher dentinal tubule density than their carnivorous relatives. We hypothesize that this relates to the hardness of the dentine, where herbivorous taxa have dentine that is more resistant to breakage and wear at the dentine-enamel junction than carnivorous taxa. This study advocates the detailed study of dentine and the use of advanced microscopy techniques to understand the evolution of dentition and feeding ecology in extinct vertebrates. © 2016 The Author(s).

Retrodeformation and muscular reconstruction of ornithomimosaurian dinosaur crania

PubMed Central

Rayfield, Emily J.

2015-01-01

Ornithomimosaur dinosaurs evolved lightweight, edentulous skulls that possessed keratinous rhamphothecae. Understanding the anatomy of these taxa allows for a greater understanding of “ostrich-mimic” dinosaurs and character change during theropod dinosaur evolution. However, taphonomic processes during fossilisation often distort fossil remains. Retrodeformation offers a means by which to recover a hypothesis of the original anatomy of the specimen, and 3D scanning technologies present a way to constrain and document the retrodeformation process. Using computed tomography (CT) scan data, specimen specific retrodeformations were performed on three-dimensionally preserved but taphonomically distorted skulls of the deinocheirid Garudimimus brevipes Barsbold, 1981 and the ornithomimids Struthiomimus altus Lambe, 1902 and Ornithomimus edmontonicus Sternberg, 1933. This allowed for a reconstruction of the adductor musculature, which was then mapped onto the crania, from which muscle mechanical advantage and bite forces were calculated pre- and post-retrodeformation. The extent of the rhamphotheca was varied in each taxon to represent morphologies found within modern Aves. Well constrained retrodeformation allows for increased confidence in anatomical and functional analysis of fossil specimens and offers an opportunity to more fully understand the soft tissue anatomy of extinct taxa. PMID:26213655

Did You Know? New Data on Dinosaurs.

ERIC Educational Resources Information Center

Silverberg, Robert

1981-01-01

New information reveals that dinosaurs have a pelvic structure similar to that of animals that walk upright. Science teachers should remember that theories and assumptions are always provisional and tentative. (JN)

Ecological Interactions in Dinosaur Communities: Influences of Small Offspring and Complex Ontogenetic Life Histories

PubMed Central

Codron, Daryl; Carbone, Chris; Clauss, Marcus

2013-01-01

Because egg-laying meant that even the largest dinosaurs gave birth to very small offspring, they had to pass through multiple ontogenetic life stages to adulthood. Dinosaurs’ successors as the dominant terrestrial vertebrate life form, the mammals, give birth to live young, and have much larger offspring and less complex ontogenetic histories. The larger number of juveniles in dinosaur as compared to mammal ecosystems represents both a greater diversity of food available to predators, and competitors for similar-sized individuals of sympatric species. Models of population abundances across different-sized species of dinosaurs and mammals, based on simulated ecological life tables, are employed to investigate how differences in predation and competition pressure influenced dinosaur communities. Higher small- to medium-sized prey availability leads to a normal body mass-species richness (M-S) distribution of carnivorous dinosaurs (as found in the theropod fossil record), in contrast to the right-skewed M-S distribution of carnivorous mammals (as found living members of the order Carnivora). Higher levels of interspecific competition leads to a left-skewed M-S distribution in herbivorous dinosaurs (as found in sauropods and ornithopods), in contrast to the normal M-S distribution of large herbivorous mammals. Thus, our models suggest that differences in reproductive strategy, and consequently ontogeny, explain observed differences in community structure between dinosaur and mammal faunas. Models also show that the largest dinosaurian predators could have subsisted on similar-sized prey by including younger life stages of the largest herbivore species, but that large predators likely avoided prey much smaller than themselves because, despite predicted higher abundances of smaller than larger-bodied prey, contributions of small prey to biomass intake would be insufficient to satisfy meat requirements. A lack of large carnivores feeding on small prey exists in mammals

Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb.

PubMed

Giachino, Claudio; Taylor, Verdon

2009-07-01

The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreER(T2) allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreER(T2)-expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreER(T2)-expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreER(T2)-targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB.

Scaling in Theropod Dinosaurs: Femoral Bone Strength and Locomotion II

NASA Astrophysics Data System (ADS)

Lee, Scott

2015-03-01

In the second paper1 of this series, the effect of transverse femoral stresses due to locomotion in theropod dinosaurs of different sizes was examined for the case of an unchanging leg geometry. Students are invariably thrilled to learn about theropod dinosaurs, and this activity applies the concepts of torque and stress to the issue of theropod locomotion. In this paper, our model calculation of Ref. 1 is extended to incorporate the fact that larger animals run with straighter legs. As in Ref. 1, students use geometric data for the femora of theropod dinosaurs to analyze their locomotion abilities. This can either be an in-class activity or given as a homework problem. Larger theropods are found to be less athletic in their movements than smaller theropods since the stresses in the femora of large theropods are closer to breaking their legs than smaller theropods.

Defining the cellular lineage hierarchy in the interfollicular epidermis of adult skin.

PubMed

Sada, Aiko; Jacob, Fadi; Leung, Eva; Wang, Sherry; White, Brian S; Shalloway, David; Tumbar, Tudorita

2016-06-01

The interfollicular epidermis regenerates from heterogeneous basal skin cell populations that divide at different rates. It has previously been presumed that infrequently dividing basal cells known as label-retaining cells (LRCs) are stem cells, whereas non-LRCs are short-lived progenitors. Here we employ the H2B-GFP pulse-chase system in adult mouse skin and find that epidermal LRCs and non-LRCs are molecularly distinct and can be differentiated by Dlx1(CreER) and Slc1a3(CreER) genetic marking, respectively. Long-term lineage tracing and mathematical modelling of H2B-GFP dilution data show that LRCs and non-LRCs constitute two distinct stem cell populations with different patterns of proliferation, differentiation and upward cellular transport. During homeostasis, these populations are enriched in spatially distinct skin territories and can preferentially produce unique differentiated lineages. On wounding or selective killing, they can temporarily replenish each other's territory. These two discrete interfollicular stem cell populations are functionally interchangeable and intrinsically well adapted to thrive in distinct skin environments.

Revisiting the Estimation of Dinosaur Growth Rates

PubMed Central

Myhrvold, Nathan P.

2013-01-01

Previous growth-rate studies covering 14 dinosaur taxa, as represented by 31 data sets, are critically examined and reanalyzed by using improved statistical techniques. The examination reveals that some previously reported results cannot be replicated by using the methods originally reported; results from new methods are in many cases different, in both the quantitative rates and the qualitative nature of the growth, from results in the prior literature. Asymptotic growth curves, which have been hypothesized to be ubiquitous, are shown to provide best fits for only four of the 14 taxa. Possible reasons for non-asymptotic growth patterns are discussed; they include systematic errors in the age-estimation process and, more likely, a bias toward younger ages among the specimens analyzed. Analysis of the data sets finds that only three taxa include specimens that could be considered skeletally mature (i.e., having attained 90% of maximum body size predicted by asymptotic curve fits), and eleven taxa are quite immature, with the largest specimen having attained less than 62% of predicted asymptotic size. The three taxa that include skeletally mature specimens are included in the four taxa that are best fit by asymptotic curves. The totality of results presented here suggests that previous estimates of both maximum dinosaur growth rates and maximum dinosaur sizes have little statistical support. Suggestions for future research are presented. PMID:24358133

Raman spectroscopy for discrimination of neural progenitor cells and their lineages (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chen, Keren; Ong, William; Chew, Sing Yian; Liu, Quan

2017-02-01

Neurological diseases are one of the leading causes of adult disability and they are estimated to cause more deaths than cancer in the elderly population by 2040. Stem cell therapy has shown great potential in treating neurological diseases. However, before cell therapy can be widely adopted in the long term, a number of challenges need to be addressed, including the fundamental research about cellular development of neural progenitor cells. To facilitate the fundamental research of neural progenitor cells, many methods have been developed to identify neural progenitor cells. Although great progress has been made, there is still lack of an effective method to achieve fast, label-free and noninvasive differentiation of neural progenitor cells and their lineages. As a fast, label-free and noninvasive technique, spontaneous Raman spectroscopy has been conducted to characterize many types of stem cells including neural stem cells. However, to our best knowledge, it has not been studied for the discrimination of neural progenitor cells from specific lineages. Here we report the differentiation of neural progenitor cell from their lineages including astrocytes, oligodendrocytes and neurons using spontaneous Raman spectroscopy. Moreover, we also evaluate the influence of system parameters during spectral acquisition on the quality of measured Raman spectra and the accuracy of classification using the spectra, which yield a set of optimal system parameters facilitating future studies.

A second look at the colors of the dinosaurs.

PubMed

Turner, Derek D

2016-02-01

In earlier work, I predicted that we would probably not be able to determine the colors of the dinosaurs. I lost this epistemic bet against science in dramatic fashion when scientists discovered that it is possible to draw inferences about dinosaur coloration based on the microstructure of fossil feathers (Vinther et al., 2008). This paper is an exercise in philosophical error analysis. I examine this episode with two questions in mind. First, does this case lend any support to epistemic optimism about historical science? Second, under what conditions is it rational to make predictions about what questions scientists will or will not be able answer? In reply to the first question, I argue that the recent work on the colors of the dinosaurs matters less to the debate about the epistemology of historical science than it might seem. In reply to the second question, I argue that it is difficult to specify a policy that would rule out the failed bet without also being too conservative. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gigantism and comparative life-history parameters of tyrannosaurid dinosaurs.

PubMed

Erickson, Gregory M; Makovicky, Peter J; Currie, Philip J; Norell, Mark A; Yerby, Scott A; Brochu, Christopher A

2004-08-12

How evolutionary changes in body size are brought about by variance in developmental timing and/or growth rates (also known as heterochrony) is a topic of considerable interest in evolutionary biology. In particular, extreme size change leading to gigantism occurred within the dinosaurs on multiple occasions. Whether this change was brought about by accelerated growth, delayed maturity or a combination of both processes is unknown. A better understanding of relationships between non-avian dinosaur groups and the newfound capacity to reconstruct their growth curves make it possible to address these questions quantitatively. Here we study growth patterns within the Tyrannosauridae, the best known group of large carnivorous dinosaurs, and determine the developmental means by which Tyrannosaurus rex, weighing 5,000 kg and more, grew to be one of the most enormous terrestrial carnivorous animals ever. T. rex had a maximal growth rate of 2.1 kg d(-1), reached skeletal maturity in two decades and lived for up to 28 years. T. rex's great stature was primarily attained by accelerating growth rates beyond that of its closest relatives.

What drove reversions to quadrupedality in ornithischian dinosaurs? Testing hypotheses using centre of mass modelling.

PubMed

Maidment, Susannah C R; Henderson, Donald M; Barrett, Paul M

2014-11-01

The exceptionally rare transition to quadrupedalism from bipedal ancestors occurred on three independent occasions in ornithischian dinosaurs. The possible driving forces behind these transitions remain elusive, but several hypotheses-including the development of dermal armour and the expansion of head size and cranial ornamentation-have been proposed to account for this major shift in stance. We modelled the position of the centre of mass (CoM) in several exemplar ornithischian taxa and demonstrate that the anterior shifts in CoM position associated with the development of an enlarged skull ornamented with horns and frills for display/defence may have been one of the drivers promoting ceratopsian quadrupedality. A posterior shift in CoM position coincident with the development of extensive dermal armour in thyreophorans demonstrates this cannot have been a primary causative mechanism for quadrupedality in this clade. Quadrupedalism developed in response to different selective pressures in each ornithischian lineage, indicating different evolutionary pathways to convergent quadrupedal morphology.

Template DNA-strand co-segregation and asymmetric cell division in skeletal muscle stem cells.

PubMed

Shinin, Vasily; Gayraud-Morel, Barbara; Tajbakhsh, Shahragim

2009-01-01

Stem cells are present in all tissues and organs, and are crucial for normal regulated growth. How the pool size of stem cells and their progeny is regulated to establish the tissue prenatally, then maintain it throughout life, is a key question in biology and medicine. The ability to precisely locate stem and progenitors requires defining lineage progression from stem to differentiated cells, assessing the mode of cell expansion and self-renewal and identifying markers to assess the different cell states within the lineage. We have shown that during lineage progression from a quiescent adult muscle satellite cell to a differentiated myofibre, both symmetric and asymmetric divisions take place. Furthermore, we provide evidence that a sub-population of label retaining satellite cells co-segregate template DNA strands to one daughter cell. These findings provide a means of identifying presumed stem and progenitor cells within the lineage. In addition, asymmetric segregation of template DNA and the cytoplasmic protein Numb provides a landmark to define cell behaviour as self-renewal and differentiation decisions are being executed.

Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells

PubMed Central

Freire-Pritchett, Paula; Schoenfelder, Stefan; Várnai, Csilla; Wingett, Steven W; Cairns, Jonathan; Collier, Amanda J; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S; Fraser, Peter; Rugg-Gunn, Peter J; Spivakov, Mikhail

2017-01-01

Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells. DOI: http://dx.doi.org/10.7554/eLife.21926.001 PMID:28332981

Ontogenetic niche shifts in dinosaurs influenced size, diversity and extinction in terrestrial vertebrates.

PubMed

Codron, Daryl; Carbone, Chris; Müller, Dennis W H; Clauss, Marcus

2012-08-23

Given the physiological limits to egg size, large-bodied non-avian dinosaurs experienced some of the most extreme shifts in size during postnatal ontogeny found in terrestrial vertebrate systems. In contrast, mammals--the other dominant vertebrate group since the Mesozoic--have less complex ontogenies. Here, we develop a model that quantifies the impact of size-specific interspecies competition on abundances of differently sized dinosaurs and mammals, taking into account the extended niche breadth realized during ontogeny among large oviparous species. Our model predicts low diversity at intermediate size classes (between approx. 1 and 1000 kg), consistent with observed diversity distributions of dinosaurs, and of Mesozoic land vertebrates in general. It also provides a mechanism--based on an understanding of different ecological and evolutionary constraints across vertebrate groups--that explains how mammals and birds, but not dinosaurs, were able to persist beyond the Cretaceous-Tertiary (K-T) boundary, and how post-K-T mammals were able to diversify into larger size categories.

Ontogenetic niche shifts in dinosaurs influenced size, diversity and extinction in terrestrial vertebrates

PubMed Central

Codron, Daryl; Carbone, Chris; Müller, Dennis W. H.; Clauss, Marcus

2012-01-01

Given the physiological limits to egg size, large-bodied non-avian dinosaurs experienced some of the most extreme shifts in size during postnatal ontogeny found in terrestrial vertebrate systems. In contrast, mammals—the other dominant vertebrate group since the Mesozoic—have less complex ontogenies. Here, we develop a model that quantifies the impact of size-specific interspecies competition on abundances of differently sized dinosaurs and mammals, taking into account the extended niche breadth realized during ontogeny among large oviparous species. Our model predicts low diversity at intermediate size classes (between approx. 1 and 1000 kg), consistent with observed diversity distributions of dinosaurs, and of Mesozoic land vertebrates in general. It also provides a mechanism—based on an understanding of different ecological and evolutionary constraints across vertebrate groups—that explains how mammals and birds, but not dinosaurs, were able to persist beyond the Cretaceous–Tertiary (K–T) boundary, and how post-K–T mammals were able to diversify into larger size categories. PMID:22513279

Isolation and functional assessment of cutaneous stem cells.

PubMed

Doucet, Yanne S; Owens, David M

2015-01-01

The epidermis and associated appendages of the skin represent a multi-lineage tissue that is maintained by perpetual rounds of renewal. During homeostasis, turnover of epidermal lineages is achieved by input from regionalized keratinocytes stem or progenitor populations with little overlap from neighboring niches. Over the last decade, molecular markers selectively expressed by a number of these stem or progenitor pools have been identified, allowing for the isolation and functional assessment of stem cells and genetic lineage tracing analysis within intact skin. These advancements have led to many fundamental observations about epidermal stem cell function such as the identification of their progeny, their role in maintenance of skin homeostasis, or their contribution to wound healing. In this chapter, we provide a methodology to identify and isolate epidermal stem cells and to assess their functional role in their respective niche. Furthermore, recent evidence has shown that the microenvironment also plays a crucial role in stem cell function. Indeed, epidermal cells are under the influence of surrounding fibroblasts, adipocytes, and sensory neurons that provide extrinsic signals and mechanical cues to the niche and contribute to skin morphogenesis and homeostasis. A better understanding of these microenvironmental cues will help engineer in vitro experimental models with more relevance to in vivo skin biology. New approaches to address and study these environmental cues in vitro will also be addressed.

Boom and bust: ancient and recent diversification in bichirs (Polypteridae: Actinopterygii), a relictual lineage of ray-finned fishes.

PubMed

Near, Thomas J; Dornburg, Alex; Tokita, Masayoshi; Suzuki, Dai; Brandley, Matthew C; Friedman, Matt

2014-04-01

Understanding the history that underlies patterns of species richness across the Tree of Life requires an investigation of the mechanisms that not only generate young species-rich clades, but also those that maintain species-poor lineages over long stretches of evolutionary time. However, diversification dynamics that underlie ancient species-poor lineages are often hidden due to a lack of fossil evidence. Using information from the fossil record and time calibrated molecular phylogenies, we investigate the history of lineage diversification in Polypteridae, which is the sister lineage of all other ray-finned fishes (Actinopterygii). Despite originating at least 390 million years (Myr) ago, molecular timetrees support a Neogene origin for the living polypterid species. Our analyses demonstrate polypterids are exceptionally species depauperate with a stem lineage duration that exceeds 380 million years (Ma) and is significantly longer than the stem lineage durations observed in other ray-finned fish lineages. Analyses of the fossil record show an early Late Cretaceous (100.5-83.6 Ma) peak in polypterid genus richness, followed by 60 Ma of low richness. The Neogene species radiation and evidence for high-diversity intervals in the geological past suggest a "boom and bust" pattern of diversification that contrasts with common perceptions of relative evolutionary stasis in so-called "living fossils." © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Bird embryos uncover homology and evolution of the dinosaur ankle.

PubMed

Ossa-Fuentes, Luis; Mpodozis, Jorge; Vargas, Alexander O

2015-11-13

The anklebone (astragalus) of dinosaurs presents a characteristic upward projection, the 'ascending process' (ASC). The ASC is present in modern birds, but develops a separate ossification centre, and projects from the calcaneum in most species. These differences have been argued to make it non-comparable to dinosaurs. We studied ASC development in six different orders of birds using traditional techniques and spin-disc microscopy for whole-mount immunofluorescence. Unexpectedly, we found the ASC derives from the embryonic intermedium, an ancient element of the tetrapod ankle. In some birds it comes in contact with the astragalus, and, in others, with the calcaneum. The fact that the intermedium fails to fuse early with the tibiale and develops an ossification centre is unlike any other amniotes, yet resembles basal, amphibian-grade tetrapods. The ASC originated in early dinosaurs along changes to upright posture and locomotion, revealing an intriguing combination of functional innovation and reversion in its evolution.

Bird embryos uncover homology and evolution of the dinosaur ankle

PubMed Central

Ossa-Fuentes, Luis; Mpodozis, Jorge; Vargas, Alexander O

2015-01-01

The anklebone (astragalus) of dinosaurs presents a characteristic upward projection, the ‘ascending process' (ASC). The ASC is present in modern birds, but develops a separate ossification centre, and projects from the calcaneum in most species. These differences have been argued to make it non-comparable to dinosaurs. We studied ASC development in six different orders of birds using traditional techniques and spin–disc microscopy for whole-mount immunofluorescence. Unexpectedly, we found the ASC derives from the embryonic intermedium, an ancient element of the tetrapod ankle. In some birds it comes in contact with the astragalus, and, in others, with the calcaneum. The fact that the intermedium fails to fuse early with the tibiale and develops an ossification centre is unlike any other amniotes, yet resembles basal, amphibian-grade tetrapods. The ASC originated in early dinosaurs along changes to upright posture and locomotion, revealing an intriguing combination of functional innovation and reversion in its evolution. PMID:26563435

Intestinal stem cells: no longer immortal but ever so clever....

PubMed

Edgar, Bruce A

2012-05-30

To maintain tissue homeostasis, stem cells must balance self-renewal with differentiation. In some stem cell lineages this process is 'hard-wired' by the asymmetric partitioning of determinants at division, such that one stem cell daughter always remains pluripotent and other differentiates. But in a dynamic tissue like the intestinal epithelium, which might need to repair itself following an infection or expand to digest the fall harvest, this balancing act requires more flexibility. Recent studies of intestinal stem cell (ISC) lineages in the fruit fly and mouse provide new insights into how this plasticity is achieved. The mechanisms in these two homologous but rather different organs have remarkable similarities, and so are likely relevant to how stem cell pools are controlled in organs other than the intestine.

Do brooding and polygamy behaviors exist on Cretaceous oviraptoroid dinosaurs of China: a paleobiological perspective

NASA Astrophysics Data System (ADS)

Yang, T.-R.; Cheng, Y.-N.; Yang, K.-M.

2012-04-01

Brooding, parental care, and polygamy represent three different stages in bird's reproduction. The oringin of these behaviors is still in debate. Several samples excavated from China strengthen the phylogenetic relationship between birds and dinosaurs, for example, feathered dinosaurs, paired-eggs in pelvic region of an oviraptorid dinosaur, and small theropod fossils. Previous studies in past two decades, including an oviraptor sitting on a clutch and comparison of the ratio of clutch-volume to adult-body-size between Aves and Mesozoic dinosaurs, proposed that these behaviors had appeared on some Cretaceous theropods (e.g., oviraptor and troodon). These researches also indicate the possibility of endothermy and male care first. In conclusion, this reproduction strategy might support females having more remnant energy to build a larger clutch contributed eggs from multiple females, and brooded by males only. From our cluster analysis through paleoecological perspectives, the eggs in Cretaceous oviraptor's nest should not be corporately laid by multiple females. In morphological observation, the fossilized clutches from Ganzhou, Jiangxi, Mainland China, are 2-layered interbeded with matrix of reddish-brown siltstone or clays. The inner-layer eggs are hampered from directly contacting with adult dinosaurs body. Furthermore, the blunt ends of the eggs point to the center, and incline away forming a mound-shape nest, which is completely different from those of precocial and male-caring megapode. The ornamentation of eggshell surface and microstructures from thin sections of eggs from oviraptors and ostrich (Struthioniformes) are totally different. Comparison of thickness in different part of oviraptor's egg also reveal possible physiological structure in the egg and ecological behaviors. The detailed comparison implies that the Mesozoic oviraptoroid dinosaurs hold absolutely different incubation and caring behaviors from extant birds. We propose an alternative

Determination of osteogenic or adipogenic lineages in muscle-derived stem cells (MDSCs) by a collagen-binding peptide (CBP) derived from bone sialoprotein (BSP).

PubMed

Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin; Chung, Chong-Pyoung; Park, Yoon Jeong

2012-03-09

Bone sialoprotein (BSP) is a mineralized, tissue-specific, non-collagenous protein that is normally expressed only in mineralized tissues such as bone, dentin, cementum, and calcified cartilage, and at sites of new mineral formation. The binding of BSP to collagen is thought to be important for initiating bone mineralization and bone cell adhesion to the mineralized matrix. Several recent studies have isolated stem cells from muscle tissue, but their functional properties are still unclear. In this study, we examined the effects of a synthetic collagen-binding peptide (CBP) on the differentiation efficiency of muscle-derived stem cells (MDSCs). The CBP sequence (NGVFKYRPRYYLYKHAYFYPHLKRFPVQ) corresponds to residues 35-62 of bone sialoprotein (BSP), which are located within the collagen-binding domain in BSP. Interestingly, this synthetic CBP inhibited adipogenic differentiation but increased osteogenic differentiation in MDSCs. The CBP also induced expression of osteoblastic marker proteins, including alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx2), and osteocalcin; prevented adipogenic differentiation in MDSCs; and down-regulated adipose-specific mRNAs, such as adipocyte protein 2 (aP2) and peroxisome proliferator-activated receptor γ. The CBP increased Extracellular signal-regulated kinases (ERK) 1/2 protein phosphorylation, which is important in lineage determination. These observations suggest that this CBP determines the osteogenic or adipogenic lineage in MDSCs by activating ERK1/2. Taken together, a novel CBP could be a useful candidate for regenerating bone and treating osteoporosis, which result from an imbalance in osteogenesis and adipogenesis differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Avian paternal care had dinosaur origin.

PubMed

Varricchio, David J; Moore, Jason R; Erickson, Gregory M; Norell, Mark A; Jackson, Frankie D; Borkowski, John J

2008-12-19

The repeated discovery of adult dinosaurs in close association with egg clutches leads to speculation over the type and extent of care exhibited by these extinct animals for their eggs and young. To assess parental care in Cretaceous troodontid and oviraptorid dinosaurs, we examined clutch volume and the bone histology of brooding adults. In comparison to four archosaur care regressions, the relatively large clutch volumes of Troodon, Oviraptor, and Citipati scale most closely with a bird-paternal care model. Clutch-associated adults lack the maternal and reproductively associated histologic features common to extant archosaurs. Large clutch volumes and a suite of reproductive features shared only with birds favor paternal care, possibly within a polygamous mating system. Paternal care in both troodontids and oviraptorids indicates that this care system evolved before the emergence of birds and represents birds' ancestral condition. In extant birds and over most adult sizes, paternal and biparental care correspond to the largest and smallest relative clutch volumes, respectively.

Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis.

PubMed

Khajuria, Rajiv K; Munschauer, Mathias; Ulirsch, Jacob C; Fiorini, Claudia; Ludwig, Leif S; McFarland, Sean K; Abdulhay, Nour J; Specht, Harrison; Keshishian, Hasmik; Mani, D R; Jovanovic, Marko; Ellis, Steven R; Fulco, Charles P; Engreitz, Jesse M; Schütz, Sabina; Lian, John; Gripp, Karen W; Weinberg, Olga K; Pinkus, Geraldine S; Gehrke, Lee; Regev, Aviv; Lander, Eric S; Gazda, Hanna T; Lee, Winston Y; Panse, Vikram G; Carr, Steven A; Sankaran, Vijay G

2018-03-22

Blood cell formation is classically thought to occur through a hierarchical differentiation process, although recent studies have shown that lineage commitment may occur earlier in hematopoietic stem and progenitor cells (HSPCs). The relevance to human blood diseases and the underlying regulation of these refined models remain poorly understood. By studying a genetic blood disorder, Diamond-Blackfan anemia (DBA), where the majority of mutations affect ribosomal proteins and the erythroid lineage is selectively perturbed, we are able to gain mechanistic insight into how lineage commitment is programmed normally and disrupted in disease. We show that in DBA, the pool of available ribosomes is limited, while ribosome composition remains constant. Surprisingly, this global reduction in ribosome levels more profoundly alters translation of a select subset of transcripts. We show how the reduced translation of select transcripts in HSPCs can impair erythroid lineage commitment, illuminating a regulatory role for ribosome levels in cellular differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

PubMed

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-04-26

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs

PubMed Central

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-01-01

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature. PMID:27112710

Stuffed Dinosaur

NASA Image and Video Library

2013-09-22

ISS037-E-002783 (22 Sept. 2013) --- NASA astronaut Karen Nyberg, Expedition 37 flight engineer, made this stuffed dinosaur toy aboard the International Space Station, using scraps of food-packaging liners and a T-shirt. She sent images of it to her young son on Sept. 22. Many of the astronaut’s hobbies lean toward artistic pursuits. She has let it be known that she loves to create different things through quilting, sewing and sketching. Nyberg took four “fat quarters” (pieces of fabric that are 18 by 22 inches) with her to the International Space Station along with needles, thread and a sketchbook when she launched to space on May 28.

The origin of the bird's beak: new insights from dinosaur incubation periods.

PubMed

Yang, Tzu-Ruei; Sander, P Martin

2018-05-01

The toothless beak of modern birds was considered as an adaption for feeding ecology; however, several recent studies suggested that developmental factors are also responsible for the toothless beak. Neontological and palaeontological studies have progressively uncovered how birds evolved toothless beaks and suggested that the multiple occurrences of complete edentulism in non-avian dinosaurs were the result of selection for specialized diets. Although developmental biology and ecological factors are not mutually exclusive, the conventional hypothesis that ecological factors account for the toothless beak appears insufficient. A recent study on dinosaur incubation period using embryonic teeth posited that tooth formation rate limits developmental speed, constraining toothed dinosaur incubation to slow reptilian rates. We suggest that selection for tooth loss was a side effect of selection for fast embryo growth and thus shorter incubation. This observation would also explain the multiple occurrences of tooth loss and beaks in non-avian dinosaur taxa crownward of Tyrannosaurus Whereas our hypothesis is an observation without any experimental supports, more studies of gene regulation of tooth formation in embryos would allow testing for the trade-off between incubation period and tooth development. © 2018 The Author(s).

mSEL-1L (Suppressor/Enhancer Lin12-like) Protein Levels Influence Murine Neural Stem Cell Self-renewal and Lineage Commitment*

PubMed Central

Cardano, Marina; Diaferia, Giuseppe R.; Cattaneo, Monica; Dessì, Sara S.; Long, Qiaoming; Conti, Luciano; DeBlasio, Pasquale; Cattaneo, Elena; Biunno, Ida

2011-01-01

Murine SEL-1L (mSEL-1L) is a key component of the endoplasmic reticulum-associated degradation pathway. It is essential during development as revealed by the multi-organ dysfunction and in uterus lethality occurring in homozygous mSEL-1L-deficient mice. Here we show that mSEL-1L is highly expressed in pluripotent embryonic stem cells and multipotent neural stem cells (NSCs) but silenced in all mature neural derivatives (i.e. astrocytes, oligodendrocytes, and neurons) by mmu-miR-183. NSCs derived from homozygous mSEL-1L-deficient embryos (mSEL-1L−/− NSCs) fail to proliferate in vitro, show a drastic reduction of the Notch effector HES-5, and reveal a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2, when compared with the wild type (mSEL-1L+/+ NSCs) counterpart. Furthermore, these cells are almost completely deprived of the neural marker Nestin, display a significant decrease of SOX-2 expression, and rapidly undergo premature astrocytic commitment and apoptosis. The data suggest severe self-renewal defects occurring in these cells probably mediated by misregulation of the Notch signaling. The results reported here denote mSEL-1L as a primitive marker with a possible involvement in the regulation of neural progenitor stemness maintenance and lineage determination. PMID:21454627

mSEL-1L (Suppressor/enhancer Lin12-like) protein levels influence murine neural stem cell self-renewal and lineage commitment.

PubMed

Cardano, Marina; Diaferia, Giuseppe R; Cattaneo, Monica; Dessì, Sara S; Long, Qiaoming; Conti, Luciano; Deblasio, Pasquale; Cattaneo, Elena; Biunno, Ida

2011-05-27

Murine SEL-1L (mSEL-1L) is a key component of the endoplasmic reticulum-associated degradation pathway. It is essential during development as revealed by the multi-organ dysfunction and in uterus lethality occurring in homozygous mSEL-1L-deficient mice. Here we show that mSEL-1L is highly expressed in pluripotent embryonic stem cells and multipotent neural stem cells (NSCs) but silenced in all mature neural derivatives (i.e. astrocytes, oligodendrocytes, and neurons) by mmu-miR-183. NSCs derived from homozygous mSEL-1L-deficient embryos (mSEL-1L(-/-) NSCs) fail to proliferate in vitro, show a drastic reduction of the Notch effector HES-5, and reveal a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2, when compared with the wild type (mSEL-1L(+/+) NSCs) counterpart. Furthermore, these cells are almost completely deprived of the neural marker Nestin, display a significant decrease of SOX-2 expression, and rapidly undergo premature astrocytic commitment and apoptosis. The data suggest severe self-renewal defects occurring in these cells probably mediated by misregulation of the Notch signaling. The results reported here denote mSEL-1L as a primitive marker with a possible involvement in the regulation of neural progenitor stemness maintenance and lineage determination.

Eat, breathe, ROS: controlling stem cell fate through metabolism.

PubMed

Kubli, Dieter A; Sussman, Mark A

2017-05-01

Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

Out of the Box Thinking: Kinematics from a 163 Million-Year-Old Dinosaur Trackway

NASA Astrophysics Data System (ADS)

Lee, Scott

2012-02-01

Dinosaurs always grab the interest of students. Information about dinosaur locomotion is accessible from the trackways they left. In a unique connection to kinematics, evidence of the acceleration of a meat-eating dinosaur (theropod) is evident in Trackway 13 in Ardley Quarry in Oxfordshire, UK. This particular trackway is described by J.J. Day, D.B. Norman, P. Upchuch and H.P. Powell in Vol. 415 of Nature on pages 494 and 495, published in 2002. This particular theropod underwent an acceleration of about g/3. This example provides a fun and engaging exercise for students studying kinematics.

Dinosaur Metabolism and the Allometry of Maximum Growth Rate

PubMed Central

Myhrvold, Nathan P.

2016-01-01

The allometry of maximum somatic growth rate has been used in prior studies to classify the metabolic state of both extant vertebrates and dinosaurs. The most recent such studies are reviewed, and their data is reanalyzed. The results of allometric regressions on growth rate are shown to depend on the choice of independent variable; the typical choice used in prior studies introduces a geometric shear transformation that exaggerates the statistical power of the regressions. The maximum growth rates of extant groups are found to have a great deal of overlap, including between groups with endothermic and ectothermic metabolism. Dinosaur growth rates show similar overlap, matching the rates found for mammals, reptiles and fish. The allometric scaling of growth rate with mass is found to have curvature (on a log-log scale) for many groups, contradicting the prevailing view that growth rate allometry follows a simple power law. Reanalysis shows that no correlation between growth rate and basal metabolic rate (BMR) has been demonstrated. These findings drive a conclusion that growth rate allometry studies to date cannot be used to determine dinosaur metabolism as has been previously argued. PMID:27828977

Dinosaur Metabolism and the Allometry of Maximum Growth Rate.

PubMed

Myhrvold, Nathan P

2016-01-01

The allometry of maximum somatic growth rate has been used in prior studies to classify the metabolic state of both extant vertebrates and dinosaurs. The most recent such studies are reviewed, and their data is reanalyzed. The results of allometric regressions on growth rate are shown to depend on the choice of independent variable; the typical choice used in prior studies introduces a geometric shear transformation that exaggerates the statistical power of the regressions. The maximum growth rates of extant groups are found to have a great deal of overlap, including between groups with endothermic and ectothermic metabolism. Dinosaur growth rates show similar overlap, matching the rates found for mammals, reptiles and fish. The allometric scaling of growth rate with mass is found to have curvature (on a log-log scale) for many groups, contradicting the prevailing view that growth rate allometry follows a simple power law. Reanalysis shows that no correlation between growth rate and basal metabolic rate (BMR) has been demonstrated. These findings drive a conclusion that growth rate allometry studies to date cannot be used to determine dinosaur metabolism as has been previously argued.

Implications of Airflow Dynamics and Soft-Tissue Reconstructions for the Heat Exchange Potential of Dinosaur Nasal Passages

NASA Astrophysics Data System (ADS)

Bourke, Jason Michael

This study seeks to restore the internal anatomy within the nasal passages of dinosaurs via the use of comparative anatomical methods along with computational fluid dynamic simulations. Nasal airway descriptions and airflow simulations are described for extant birds, crocodylians, and lizards. These descriptions served as a baseline for airflow within the nasal passages of diapsids. The presence of shared airflow and soft-tissue properties found in the nasal passages of extant diapsids, were used to restore soft tissues within the airways of dinosaurs under the assumption that biologically unfeasible airflow patterns (e.g., lack of air movement in olfactory recess) can serve as signals for missing soft tissues. This methodology was tested on several dinosaur taxa. Restored airways in some taxa revealed the potential presence and likely shape of nasal turbinates. Heat transfer efficiency was tested in two dinosaur species with elaborated nasal passages. Results of that analysis revealed that dinosaur noses were efficient heat exchangers that likely played an integral role in maintaining cephalic thermoregulation. Brain cooling via nasal expansion appears to have been necessary for dinosaurs to have achieved their immense body sizes without overheating their brains.

Hematopoiesis: an evolving paradigm for stem cell biology.

PubMed

Orkin, Stuart H; Zon, Leonard I

2008-02-22

Establishment and maintenance of the blood system relies on self-renewing hematopoietic stem cells (HSCs) that normally reside in small numbers in the bone marrow niche of adult mammals. This Review describes the developmental origins of HSCs and the molecular mechanisms that regulate lineage-specific differentiation. Studies of hematopoiesis provide critical insights of general relevance to other areas of stem cell biology including the role of cellular interactions in development and tissue homeostasis, lineage programming and reprogramming by transcription factors, and stage- and age-specific differences in cellular phenotypes.

Epidermal stem cells: location, potential and contribution to cancer.

PubMed

Ambler, C A; Määttä, A

2009-01-01

Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

A mummified duck-billed dinosaur with a soft-tissue cock's comb.

PubMed

Bell, Phil R; Fanti, Federico; Currie, Philip J; Arbour, Victoria M

2014-01-06

Among living vertebrates, soft tissues are responsible for labile appendages (combs, wattles, proboscides) that are critical for activities ranging from locomotion to sexual display [1]. However, soft tissues rarely fossilize, and such soft-tissue appendages are unknown for many extinct taxa, including dinosaurs. Here we report a remarkable "mummified" specimen of the hadrosaurid dinosaur Edmontosaurus regalis from the latest Cretaceous Wapiti Formation, Alberta, Canada, that preserves a three-dimensional cranial crest (or "comb") composed entirely of soft tissue. Previously, crest function has centered on the hypertrophied nasal passages of lambeosaurine hadrosaurids, which acted as resonance chambers during vocalization [2-4]. The fleshy comb in Edmontosaurus necessitates an alternative explanation most likely related to either social signaling or sexual selection [5-7]. This discovery provides the first view of bizarre, soft-tissue signaling structures in a dinosaur and provides additional evidence for social behavior. Crest evolution within Hadrosaurinae apparently culminated in the secondary loss of the bony crest at the terminal Cretaceous; however, the new specimen indicates that cranial ornamentation was in fact not lost but substituted in Edmontosaurus by a fleshy display structure. It also implies that visual display played a key role in the evolution of hadrosaurine crests and raises the possibility of similar soft-tissue structures among other dinosaurs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cretaceous anuran and dinosaur footprints from the Patuxent Formation of Virginia

USGS Publications Warehouse

Weems, R.E.; Bachman, J.M.

1997-01-01

Footprints of an anuran (gen. et sp. indet.), a theropod dinosaur (Megalosauropus sp.), and an ornithopod dinosaur (Amblydactylus sp.) have been recovered from the Lower Cretaceous Patuxent Formation in Stafford County, Virginia. These footprints are the first record of terrestrial vertebrates from Cretaceous strata in Virginia, and their discovery suggests that the scarcity of bones and teeth in the Patuxent probably is an artifact of preservation. The anuran trackway provides the oldest known direct evidence for hopping locomotion among these amphibians.

Models for the rise of the dinosaurs.

PubMed

Benton, Michael J; Forth, Jonathan; Langer, Max C

2014-01-20

Dinosaurs arose in the early Triassic in the aftermath of the greatest mass extinction ever and became hugely successful in the Mesozoic. Their initial diversification is a classic example of a large-scale macroevolutionary change. Diversifications at such deep-time scales can now be dissected, modelled and tested. New fossils suggest that dinosaurs originated early in the Middle Triassic, during the recovery of life from the devastating Permo-Triassic mass extinction. Improvements in stratigraphic dating and a new suite of morphometric and comparative evolutionary numerical methods now allow a forensic dissection of one of the greatest turnovers in the history of life. Such studies mark a move from the narrative to the analytical in macroevolutionary research, and they allow us to begin to answer the proposal of George Gaylord Simpson, to explore adaptive radiations using numerical methods. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Induced pluripotent stem (iPS) cells from human fetal stem cells.

PubMed

Guillot, Pascale V

2016-02-01

Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Extreme ecosystem instability suppressed tropical dinosaur dominance for 30 million years.

PubMed

Whiteside, Jessica H; Lindström, Sofie; Irmis, Randall B; Glasspool, Ian J; Schaller, Morgan F; Dunlavey, Maria; Nesbitt, Sterling J; Smith, Nathan D; Turner, Alan H

2015-06-30

A major unresolved aspect of the rise of dinosaurs is why early dinosaurs and their relatives were rare and species-poor at low paleolatitudes throughout the Late Triassic Period, a pattern persisting 30 million years after their origin and 10-15 million years after they became abundant and speciose at higher latitudes. New palynological, wildfire, organic carbon isotope, and atmospheric pCO2 data from early dinosaur-bearing strata of low paleolatitudes in western North America show that large, high-frequency, tightly correlated variations in δ(13)Corg and palynomorph ecotypes occurred within a context of elevated and increasing pCO2 and pervasive wildfires. Whereas pseudosuchian archosaur-dominated communities were able to persist in these same regions under rapidly fluctuating extreme climatic conditions until the end-Triassic, large-bodied, fast-growing tachymetabolic dinosaurian herbivores requiring greater resources were unable to adapt to unstable high CO2 environmental conditions of the Late Triassic.

Extreme ecosystem instability suppressed tropical dinosaur dominance for 30 million years

NASA Astrophysics Data System (ADS)

Whiteside, Jessica H.; Lindström, Sofie; Irmis, Randall B.; Glasspool, Ian J.; Schaller, Morgan F.; Dunlavey, Maria; Nesbitt, Sterling J.; Smith, Nathan D.; Turner, Alan H.

2015-06-01

A major unresolved aspect of the rise of dinosaurs is why early dinosaurs and their relatives were rare and species-poor at low paleolatitudes throughout the Late Triassic Period, a pattern persisting 30 million years after their origin and 10-15 million years after they became abundant and speciose at higher latitudes. New palynological, wildfire, organic carbon isotope, and atmospheric pCO2 data from early dinosaur-bearing strata of low paleolatitudes in western North America show that large, high-frequency, tightly correlated variations in δ13Corg and palynomorph ecotypes occurred within a context of elevated and increasing pCO2 and pervasive wildfires. Whereas pseudosuchian archosaur-dominated communities were able to persist in these same regions under rapidly fluctuating extreme climatic conditions until the end-Triassic, large-bodied, fast-growing tachymetabolic dinosaurian herbivores requiring greater resources were unable to adapt to unstable high CO2 environmental conditions of the Late Triassic.

Extreme ecosystem instability suppressed tropical dinosaur dominance for 30 million years

PubMed Central

Whiteside, Jessica H.; Lindström, Sofie; Irmis, Randall B.; Glasspool, Ian J.; Schaller, Morgan F.; Dunlavey, Maria; Nesbitt, Sterling J.; Smith, Nathan D.; Turner, Alan H.

2015-01-01

A major unresolved aspect of the rise of dinosaurs is why early dinosaurs and their relatives were rare and species-poor at low paleolatitudes throughout the Late Triassic Period, a pattern persisting 30 million years after their origin and 10–15 million years after they became abundant and speciose at higher latitudes. New palynological, wildfire, organic carbon isotope, and atmospheric pCO2 data from early dinosaur-bearing strata of low paleolatitudes in western North America show that large, high-frequency, tightly correlated variations in δ13Corg and palynomorph ecotypes occurred within a context of elevated and increasing pCO2 and pervasive wildfires. Whereas pseudosuchian archosaur-dominated communities were able to persist in these same regions under rapidly fluctuating extreme climatic conditions until the end-Triassic, large-bodied, fast-growing tachymetabolic dinosaurian herbivores requiring greater resources were unable to adapt to unstable high CO2 environmental conditions of the Late Triassic. PMID:26080428

Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

PubMed Central

Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

2016-01-01

ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

Dinosaurs in decline tens of millions of years before their final extinction

PubMed Central

Sakamoto, Manabu; Benton, Michael J.; Venditti, Chris

2016-01-01

Whether dinosaurs were in a long-term decline or whether they were reigning strong right up to their final disappearance at the Cretaceous–Paleogene (K-Pg) mass extinction event 66 Mya has been debated for decades with no clear resolution. The dispute has continued unresolved because of a lack of statistical rigor and appropriate evolutionary framework. Here, for the first time to our knowledge, we apply a Bayesian phylogenetic approach to model the evolutionary dynamics of speciation and extinction through time in Mesozoic dinosaurs, properly taking account of previously ignored statistical violations. We find overwhelming support for a long-term decline across all dinosaurs and within all three dinosaurian subclades (Ornithischia, Sauropodomorpha, and Theropoda), where speciation rate slowed down through time and was ultimately exceeded by extinction rate tens of millions of years before the K-Pg boundary. The only exceptions to this general pattern are the morphologically specialized herbivores, the Hadrosauriformes and Ceratopsidae, which show rapid species proliferations throughout the Late Cretaceous instead. Our results highlight that, despite some heterogeneity in speciation dynamics, dinosaurs showed a marked reduction in their ability to replace extinct species with new ones, making them vulnerable to extinction and unable to respond quickly to and recover from the final catastrophic event. PMID:27092007

Dinosaurs in decline tens of millions of years before their final extinction.

PubMed

Sakamoto, Manabu; Benton, Michael J; Venditti, Chris

2016-05-03

Whether dinosaurs were in a long-term decline or whether they were reigning strong right up to their final disappearance at the Cretaceous-Paleogene (K-Pg) mass extinction event 66 Mya has been debated for decades with no clear resolution. The dispute has continued unresolved because of a lack of statistical rigor and appropriate evolutionary framework. Here, for the first time to our knowledge, we apply a Bayesian phylogenetic approach to model the evolutionary dynamics of speciation and extinction through time in Mesozoic dinosaurs, properly taking account of previously ignored statistical violations. We find overwhelming support for a long-term decline across all dinosaurs and within all three dinosaurian subclades (Ornithischia, Sauropodomorpha, and Theropoda), where speciation rate slowed down through time and was ultimately exceeded by extinction rate tens of millions of years before the K-Pg boundary. The only exceptions to this general pattern are the morphologically specialized herbivores, the Hadrosauriformes and Ceratopsidae, which show rapid species proliferations throughout the Late Cretaceous instead. Our results highlight that, despite some heterogeneity in speciation dynamics, dinosaurs showed a marked reduction in their ability to replace extinct species with new ones, making them vulnerable to extinction and unable to respond quickly to and recover from the final catastrophic event.

Dinosaurs in decline tens of millions of years before their final extinction

NASA Astrophysics Data System (ADS)

Sakamoto, Manabu; Benton, Michael J.

2016-05-01

Whether dinosaurs were in a long-term decline or whether they were reigning strong right up to their final disappearance at the Cretaceous-Paleogene (K-Pg) mass extinction event 66 Mya has been debated for decades with no clear resolution. The dispute has continued unresolved because of a lack of statistical rigor and appropriate evolutionary framework. Here, for the first time to our knowledge, we apply a Bayesian phylogenetic approach to model the evolutionary dynamics of speciation and extinction through time in Mesozoic dinosaurs, properly taking account of previously ignored statistical violations. We find overwhelming support for a long-term decline across all dinosaurs and within all three dinosaurian subclades (Ornithischia, Sauropodomorpha, and Theropoda), where speciation rate slowed down through time and was ultimately exceeded by extinction rate tens of millions of years before the K-Pg boundary. The only exceptions to this general pattern are the morphologically specialized herbivores, the Hadrosauriformes and Ceratopsidae, which show rapid species proliferations throughout the Late Cretaceous instead. Our results highlight that, despite some heterogeneity in speciation dynamics, dinosaurs showed a marked reduction in their ability to replace extinct species with new ones, making them vulnerable to extinction and unable to respond quickly to and recover from the final catastrophic event.

The last dinosaurs of Brazil: The Bauru Group and its implications for the end-Cretaceous mass extinction.

PubMed

Brusatte, Stephen L; Candeiro, Carlos R A; Simbras, Felipe M

2017-01-01

The non-avian dinosaurs died out at the end of the Cretaceous, ~66 million years ago, after an asteroid impact. The prevailing hypothesis is that the effects of the impact suddenly killed the dinosaurs, but the poor fossil record of latest Cretaceous (Campanian-Maastrichtian) dinosaurs from outside Laurasia (and even more particularly, North America) makes it difficult to test specific extinction scenarios. Over the past few decades, a wealth of new discoveries from the Bauru Group of Brazil has revealed a unique window into the evolution of terminal Cretaceous dinosaurs from the southern continents. We review this record and demonstrate that there was a diversity of dinosaurs, of varying body sizes, diets, and ecological roles, that survived to the very end of the Cretaceous (Maastrichtian: 72-66 million years ago) in Brazil, including a core fauna of titanosaurian sauropods and abelisaurid and carcharodontosaurid theropods, along with a variety of small-to-mid-sized theropods. We argue that this pattern best fits the hypothesis that southern dinosaurs, like their northern counterparts, were still diversifying and occupying prominent roles in their ecosystems before the asteroid suddenly caused their extinction. However, this hypothesis remains to be tested with more refined paleontological and geochronological data, and we give suggestions for future work.

Feedback, Lineages and Self-Organizing Morphogenesis

PubMed Central

Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

2016-01-01

Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

Dysregulation of haematopoietic stem cell regulatory programs in acute myeloid leukaemia.

PubMed

Basilico, Silvia; Göttgens, Berthold

2017-07-01

Haematopoietic stem cells (HSC) are situated at the apex of the haematopoietic differentiation hierarchy, ensuring the life-long supply of mature haematopoietic cells and forming a reservoir to replenish the haematopoietic system in case of emergency such as acute blood loss. To maintain a balanced production of all mature lineages and at the same time secure a stem cell reservoir, intricate regulatory programs have evolved to control multi-lineage differentiation and self-renewal in haematopoietic stem and progenitor cells (HSPCs). Leukaemogenic mutations commonly disrupt these regulatory programs causing a block in differentiation with simultaneous enhancement of proliferation. Here, we briefly summarize key aspects of HSPC regulatory programs, and then focus on their disruption by leukaemogenic fusion genes containing the mixed lineage leukaemia (MLL) gene. Using MLL as an example, we explore important questions of wider significance that are still under debate, including the importance of cell of origin, to what extent leukaemia oncogenes impose specific regulatory programs and the relevance of leukaemia stem cells for disease development and prognosis. Finally, we suggest that disruption of stem cell regulatory programs is likely to play an important role in many other pathologies including ageing-associated regenerative failure.

Eat, breathe, ROS: controlling stem cell fate through metabolism

PubMed Central

Kubli, Dieter A.; Sussman, Mark A.

2017-01-01

Introduction Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes. PMID:28406333

Dnmt1 regulates the myogenic lineage specification of muscle stem cells.

PubMed

Liu, Renjing; Kim, Kun-Yong; Jung, Yong-Wook; Park, In-Hyun

2016-10-18

DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle. These mice were born runted, with smaller body weights, and reduced ability to form myotubes in vitro. We show that expression of Id-1, a negative regulator of myogenesis, is enhanced in Dnmt1-deficient cultures, leading to enhanced transdifferentiation of myoblasts toward the osteogenic lineage. Thus, these studies demonstrate that Dnmt1 influences cellular identity and determines lineage fidelity.

Dnmt1 regulates the myogenic lineage specification of muscle stem cells

PubMed Central

Liu, Renjing; Kim, Kun-Yong; Jung, Yong-Wook; Park, In-Hyun

2016-01-01

DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle. These mice were born runted, with smaller body weights, and reduced ability to form myotubes in vitro. We show that expression of Id-1, a negative regulator of myogenesis, is enhanced in Dnmt1-deficient cultures, leading to enhanced transdifferentiation of myoblasts toward the osteogenic lineage. Thus, these studies demonstrate that Dnmt1 influences cellular identity and determines lineage fidelity. PMID:27752090

Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios.

PubMed

Hoppe, Philipp S; Schwarzfischer, Michael; Loeffler, Dirk; Kokkaliaris, Konstantinos D; Hilsenbeck, Oliver; Moritz, Nadine; Endele, Max; Filipczyk, Adam; Gambardella, Adriana; Ahmed, Nouraiz; Etzrodt, Martin; Coutu, Daniel L; Rieger, Michael A; Marr, Carsten; Strasser, Michael K; Schauberger, Bernhard; Burtscher, Ingo; Ermakova, Olga; Bürger, Antje; Lickert, Heiko; Nerlov, Claus; Theis, Fabian J; Schroeder, Timm

2016-07-14

The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described as being expressed in uncommitted cell populations. This led to the assumption that lineage choice is cell-intrinsically initiated and determined by stochastic switches of randomly fluctuating cross-antagonistic transcription factors. However, this hypothesis was developed on the basis of RNA expression data from snapshot and/or population-averaged analyses. Alternative models of lineage choice therefore cannot be excluded. Here we use novel reporter mouse lines and live imaging for continuous single-cell long-term quantification of the transcription factors GATA1 and PU.1 (also known as SPI1). We analyse individual haematopoietic stem cells throughout differentiation into megakaryocytic-erythroid and granulocytic-monocytic lineages. The observed expression dynamics are incompatible with the assumption that stochastic switching between PU.1 and GATA1 precedes and initiates megakaryocytic-erythroid versus granulocytic-monocytic lineage decision-making. Rather, our findings suggest that these transcription factors are only executing and reinforcing lineage choice once made. These results challenge the current prevailing model of early myeloid lineage choice.

The First Dinosaur from Washington State and a Review of Pacific Coast Dinosaurs from North America

PubMed Central

2015-01-01

We describe the first diagnostic dinosaur fossil from Washington State. The specimen, which consists of a proximal left femur, was recovered from the shallow marine rocks of the Upper Cretaceous (Campanian) Cedar District Formation (Nanaimo Group) and is interpreted as pertaining to a large theropod on the basis of its hollow medullary cavity and proximally placed fourth trochanter. The Washington theropod represents one of the northernmost occurrences of a Mesozoic dinosaur on the west coast of the United States and one of only a handful from the Pacific coast of Laramidia during the Cretaceous. Its isolated nature and preservation in marine rocks suggest that the element was washed in from a nearby fluvial system. If the femur pertains to a tyrannosauroid, which seems likely given its size and the widespread occurrence of the group across Laramidia during Late Cretaceous times, then it would represent an earlier occurrence of large body size than previously recognized (complete femur length estimated at 1.2 meters). Uncertainty surrounding the latitude of deposition of the Nanaimo Group (i.e., the Baja-British Columbia hypothesis) precludes assigning the Washington theropod to either of the putative northern or southern biogeographic provinces of Laramidia. PMID:25993090

The first dinosaur from Washington State and a review of Pacific coast dinosaurs from North America.

PubMed

Peecook, Brandon R; Sidor, Christian A

2015-01-01

We describe the first diagnostic dinosaur fossil from Washington State. The specimen, which consists of a proximal left femur, was recovered from the shallow marine rocks of the Upper Cretaceous (Campanian) Cedar District Formation (Nanaimo Group) and is interpreted as pertaining to a large theropod on the basis of its hollow medullary cavity and proximally placed fourth trochanter. The Washington theropod represents one of the northernmost occurrences of a Mesozoic dinosaur on the west coast of the United States and one of only a handful from the Pacific coast of Laramidia during the Cretaceous. Its isolated nature and preservation in marine rocks suggest that the element was washed in from a nearby fluvial system. If the femur pertains to a tyrannosauroid, which seems likely given its size and the widespread occurrence of the group across Laramidia during Late Cretaceous times, then it would represent an earlier occurrence of large body size than previously recognized (complete femur length estimated at 1.2 meters). Uncertainty surrounding the latitude of deposition of the Nanaimo Group (i.e., the Baja-British Columbia hypothesis) precludes assigning the Washington theropod to either of the putative northern or southern biogeographic provinces of Laramidia.

Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.

PubMed

Barker, Nick; Rookmaaker, Maarten B; Kujala, Pekka; Ng, Annie; Leushacke, Marc; Snippert, Hugo; van de Wetering, Marc; Tan, Shawna; Van Es, Johan H; Huch, Meritxell; Poulsom, Richard; Verhaar, Marianne C; Peters, Peter J; Clevers, Hans

2012-09-27

Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and localization of Lgr5(+ve) cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Prospecting for dinosaurs on the mining frontier: The value of information in America's Gilded Age.

PubMed

Rieppel, Lukas

2015-04-01

How much is a dinosaur worth? This essay offers an account of the way vertebrate fossils were priced in late 19th-century America to explore the process by which monetary values are established in science. Examining a long and drawn-out negotiation over the sale of an unusually rich dinosaur quarry in Wyoming, I argue that, on their own, abstract market principles did not suffice to mediate between supply and demand. Rather, people haggling over the price of dinosaur bones looked to social norms from the mineral industry for cues on how to value these rare and unusual objects, adopting a set of negotiation tactics that exploited asymmetries in the distribution of scarce information to secure the better end of the deal. On the mining frontier in America's Gilded Age, dinosaurs were thus valued in much the same way as any other scarce natural resource one could dig out of the ground, including gold, silver, and coal.

Dinosaur origin of egg color: oviraptors laid blue-green eggs

PubMed Central

Yang, Tzu-Ruei; Sander, Philipp N.; Schneider, Marion; Engeser, Marianne; Kath-Schorr, Stephanie; Müller, Christa E.; Sander, P. Martin

2017-01-01

Protoporphyrin (PP) and biliverdin (BV) give rise to the enormous diversity in avian egg coloration. Egg color serves several ecological purposes, including post-mating signaling and camouflage. Egg camouflage represents a major character of open-nesting birds which accomplish protection of their unhatched offspring against visually oriented predators by cryptic egg coloration. Cryptic coloration evolved to match the predominant shades of color found in the nesting environment. Such a selection pressure for the evolution of colored or cryptic eggs should be present in all open nesting birds and relatives. Many birds are open-nesting, but protect their eggs by continuous brooding, and thus exhibit no or minimal eggshell pigmentation. Their closest extant relatives, crocodiles, protect their eggs by burial and have unpigmented eggs. This phylogenetic pattern led to the assumption that colored eggs evolved within crown birds. The mosaic evolution of supposedly avian traits in non-avian theropod dinosaurs, however, such as the supposed evolution of partially open nesting behavior in oviraptorids, argues against this long-established theory. Using a double-checking liquid chromatography ESI-Q-TOF mass spectrometry routine, we traced the origin of colored eggs to their non-avian dinosaur ancestors by providing the first record of the avian eggshell pigments protoporphyrin and biliverdin in the eggshells of Late Cretaceous oviraptorid dinosaurs. The eggshell parataxon Macroolithus yaotunensis can be assigned to the oviraptor Heyuannia huangi based on exceptionally preserved, late developmental stage embryo remains. The analyzed eggshells are from three Late Cretaceous fluvial deposits ranging from eastern to southernmost China. Reevaluation of these taphonomic settings, and a consideration of patterns in the porosity of completely preserved eggs support an at least partially open nesting behavior for oviraptorosaurs. Such a nest arrangement corresponds with our

Dinosaur origin of egg color: oviraptors laid blue-green eggs.

PubMed

Wiemann, Jasmina; Yang, Tzu-Ruei; Sander, Philipp N; Schneider, Marion; Engeser, Marianne; Kath-Schorr, Stephanie; Müller, Christa E; Sander, P Martin

2017-01-01

Protoporphyrin (PP) and biliverdin (BV) give rise to the enormous diversity in avian egg coloration. Egg color serves several ecological purposes, including post-mating signaling and camouflage. Egg camouflage represents a major character of open-nesting birds which accomplish protection of their unhatched offspring against visually oriented predators by cryptic egg coloration. Cryptic coloration evolved to match the predominant shades of color found in the nesting environment. Such a selection pressure for the evolution of colored or cryptic eggs should be present in all open nesting birds and relatives. Many birds are open-nesting, but protect their eggs by continuous brooding, and thus exhibit no or minimal eggshell pigmentation. Their closest extant relatives, crocodiles, protect their eggs by burial and have unpigmented eggs. This phylogenetic pattern led to the assumption that colored eggs evolved within crown birds. The mosaic evolution of supposedly avian traits in non-avian theropod dinosaurs, however, such as the supposed evolution of partially open nesting behavior in oviraptorids, argues against this long-established theory. Using a double-checking liquid chromatography ESI-Q-TOF mass spectrometry routine, we traced the origin of colored eggs to their non-avian dinosaur ancestors by providing the first record of the avian eggshell pigments protoporphyrin and biliverdin in the eggshells of Late Cretaceous oviraptorid dinosaurs. The eggshell parataxon Macroolithus yaotunensis can be assigned to the oviraptor Heyuannia huangi based on exceptionally preserved, late developmental stage embryo remains. The analyzed eggshells are from three Late Cretaceous fluvial deposits ranging from eastern to southernmost China. Reevaluation of these taphonomic settings, and a consideration of patterns in the porosity of completely preserved eggs support an at least partially open nesting behavior for oviraptorosaurs. Such a nest arrangement corresponds with our

Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells.

PubMed

Barbet, Romain; Peiffer, Isabelle; Hatzfeld, Antoinette; Charbord, Pierre; Hatzfeld, Jacques A

2011-01-01

We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated that hES-MSCs express the sarcomeric muscle lineage in addition to the classical mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript analysis of membrane antigens suggests that IL1R1(low), BMPR1B(low), FLT4(low), LRRC32(low), and CD34 may be good candidates for the detection and isolation of the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6, IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role for these cytokines in the paracrine control of stem cell niches. Our database may be shared with other laboratories in order to explore the considerable clinical potential of hES-MSCs, which appear to represent an intermediate developmental stage between hESCs and hMSCs.

Maximal aerobic and anaerobic power generation in large crocodiles versus mammals: implications for dinosaur gigantothermy.

PubMed

Seymour, Roger S

2013-01-01

Inertial homeothermy, the maintenance of a relatively constant body temperature that occurs simply because of large size, is often applied to large dinosaurs. Moreover, biophysical modelling and actual measurements show that large crocodiles can behaviourally achieve body temperatures above 30°C. Therefore it is possible that some dinosaurs could achieve high and stable body temperatures without the high energy cost of typical endotherms. However it is not known whether an ectothermic dinosaur could produce the equivalent amount of muscular power as an endothermic one. To address this question, this study analyses maximal power output from measured aerobic and anaerobic metabolism in burst exercising estuarine crocodiles, Crocodylusporosus, weighing up to 200 kg. These results are compared with similar data from endothermic mammals. A 1 kg crocodile at 30°C produces about 16 watts from aerobic and anaerobic energy sources during the first 10% of exhaustive activity, which is 57% of that expected for a similarly sized mammal. A 200 kg crocodile produces about 400 watts, or only 14% of that for a mammal. Phosphocreatine is a minor energy source, used only in the first seconds of exercise and of similar concentrations in reptiles and mammals. Ectothermic crocodiles lack not only the absolute power for exercise, but also the endurance, that are evident in endothermic mammals. Despite the ability to achieve high and fairly constant body temperatures, therefore, large, ectothermic, crocodile-like dinosaurs would have been competitively inferior to endothermic, mammal-like dinosaurs with high aerobic power. Endothermy in dinosaurs is likely to explain their dominance over mammals in terrestrial ecosystems throughout the Mesozoic.

Maximal Aerobic and Anaerobic Power Generation in Large Crocodiles versus Mammals: Implications for Dinosaur Gigantothermy

PubMed Central

Seymour, Roger S.

2013-01-01

Inertial homeothermy, the maintenance of a relatively constant body temperature that occurs simply because of large size, is often applied to large dinosaurs. Moreover, biophysical modelling and actual measurements show that large crocodiles can behaviourally achieve body temperatures above 30°C. Therefore it is possible that some dinosaurs could achieve high and stable body temperatures without the high energy cost of typical endotherms. However it is not known whether an ectothermic dinosaur could produce the equivalent amount of muscular power as an endothermic one. To address this question, this study analyses maximal power output from measured aerobic and anaerobic metabolism in burst exercising estuarine crocodiles, Crocodylusporosus , weighing up to 200 kg. These results are compared with similar data from endothermic mammals. A 1 kg crocodile at 30°C produces about 16 watts from aerobic and anaerobic energy sources during the first 10% of exhaustive activity, which is 57% of that expected for a similarly sized mammal. A 200 kg crocodile produces about 400 watts, or only 14% of that for a mammal. Phosphocreatine is a minor energy source, used only in the first seconds of exercise and of similar concentrations in reptiles and mammals. Ectothermic crocodiles lack not only the absolute power for exercise, but also the endurance, that are evident in endothermic mammals. Despite the ability to achieve high and fairly constant body temperatures, therefore, large, ectothermic, crocodile-like dinosaurs would have been competitively inferior to endothermic, mammal-like dinosaurs with high aerobic power. Endothermy in dinosaurs is likely to explain their dominance over mammals in terrestrial ecosystems throughout the Mesozoic. PMID:23861968

Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells

PubMed Central

2013-01-01

Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells. PMID:23796405

Cretaceous origin of the unique prey-capture apparatus in mega-diverse genus: stem lineage of Steninae rove beetles discovered in Burmese amber

PubMed Central

Żyła, Dagmara; Yamamoto, Shûhei; Wolf-Schwenninger, Karin; Solodovnikov, Alexey

2017-01-01

Stenus is the largest genus of rove beetles and the second largest among animals. Its evolutionary success was associated with the adhesive labial prey-capture apparatus, a unique apomorphy of that genus. Definite Stenus with prey-capture apparatus are known from the Cenozoic fossils, while the age and early evolution of Steninae was hardly ever hypothesized. Our study of several Cretaceous Burmese amber inclusions revealed a stem lineage of Steninae that possibly possesses the Stenus-like prey-capture apparatus. Phylogenetic analysis of extinct and extant taxa of Steninae and putatively allied subfamilies of Staphylinidae with parsimony and Bayesian approaches resolved the Burmese amber lineage as a member of Steninae. It justified the description of a new extinct stenine genus Festenus with two new species, F. robustus and F. gracilis. The Late Cretaceous age of Festenus suggests an early origin of prey-capture apparatus in Steninae that, perhaps, drove the evolution towards the crown Stenus. Our analysis confirmed the well-established sister relationships between Steninae and Euaesthetinae and resolved Scydmaeninae as their next closest relative, the latter having no stable position in recent phylogenetic studies of rove beetles. Close affiliation of Megalopsidiinae, a subfamily often considered as a sister group to Euaesthetinae + Steninae clade, is rejected. PMID:28397786

Integrin Based Isolation Enables Purification of Murine Lineage Committed Cardiomyocytes

PubMed Central

Tarnawski, Laura; Xian, Xiaojie; Monnerat, Gustavo; Macaulay, Iain C.; Malan, Daniela; Borgman, Andrew; Wu, Sean M.; Fleischmann, Bernd K.; Jovinge, Stefan

2015-01-01

In contrast to mature cardiomyocytes which have limited regenerative capacity, pluripotent stem cells represent a promising source for the generation of new cardiomyocytes. The tendency of pluripotent stem cells to form teratomas and the heterogeneity from various differentiation stages and cardiomyocyte cell sub-types, however, are major obstacles to overcome before this type of therapy could be applied in a clinical setting. Thus, the identification of extracellular markers for specific cardiomyocyte progenitors and mature subpopulations is of particular importance. The delineation of cardiomyocyte surface marker patterns not only serves as a means to derive homogeneous cell populations by FACS, but is also an essential tool to understand cardiac development. By using single-cell expression profiling in early mouse embryonic hearts, we found that a combination of integrin alpha-1, alpha-5, alpha-6 and N-cadherin enables isolation of lineage committed murine cardiomyocytes. Additionally, we were able to separate trabecular cardiomyocytes from solid ventricular myocardium and atrial murine cells. These cells exhibit expected subtype specific phenotype confirmed by electrophysiological analysis. We show that integrin expression can be used for the isolation of living, functional and lineage-specific murine cardiomyocytes. PMID:26323090

Human Induced Hepatic Lineage-Oriented Stem Cells: Autonomous Specification of Human iPS Cells toward Hepatocyte-Like Cells without Any Exogenous Differentiation Factors

PubMed Central

Yanagi, Satoshi; Kato, Chika; Takashima, Ryokichi; Kobayashi, Eiji; Hagiwara, Keitaro; Ochiya, Takahiro

2015-01-01

Preparing targeted cells for medical applications from human induced pluripotent stem cells (hiPSCs) using growth factors, compounds, or gene transfer has been challenging. Here, we report that human induced hepatic lineage-oriented stem cells (hiHSCs) were generated and expanded as a new type of hiPSC under non-typical coculture with feeder cells in a chemically defined hiPSC medium at a very high density. Self-renewing hiHSCs expressed markers of both human embryonic stem cells (hESCs) and hepatocytes. Those cells were highly expandable, markedly enhancing gene expression of serum hepatic proteins and cytochrome P450 enzymes with the omission of FGF-2 from an undefined hiPSC medium. The hepatic specification of hiHSCs was not attributable to the genetic and epigenetic backgrounds of the starting cells, as they were established from distinct donors and different types of cells. Approximately 90% of hiHSCs autonomously differentiated to hepatocyte-like cells, even in a defined minimum medium without any of the exogenous growth factors necessary for hepatic specification. After 12 days of this culture, the differentiated cells significantly enhanced gene expression of serum hepatic proteins (ALB, SERPINA1, TTR, TF, FABP1, FGG, AGT, RBP4, and AHSG), conjugating enzymes (UGT2B4, UGT2B7, UGT2B10, GSTA2, and GSTA5), transporters (SULT2A1, SLC13A5, and SLCO2B1), and urea cycle-related enzymes (ARG1 and CPS1). In addition, the hepatocyte-like cells performed key functions of urea synthesis, albumin secretion, glycogen storage, indocyanine green uptake, and low-density lipoprotein uptake. The autonomous hepatic specification of hiHSCs was due to their culture conditions (coculture with feeder cells in a defined hiPSC medium at a very high density) in self-renewal rather than in differentiation. These results suggest the feasibility of preparing large quantities of hepatocytes as a convenient and inexpensive hiPSC differentiation. Our study also suggests the necessity of

The functional and palaeoecological implications of tooth morphology and wear for the megaherbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta, Canada.

PubMed

Mallon, Jordan C; Anderson, Jason S

2014-01-01

Megaherbivorous dinosaurs were exceptionally diverse on the Late Cretaceous island continent of Laramidia, and a growing body of evidence suggests that this diversity was facilitated by dietary niche partitioning. We test this hypothesis using the fossil megaherbivore assemblage from the Dinosaur Park Formation (upper Campanian) of Alberta as a model. Comparative tooth morphology and wear, including the first use of quantitative dental microwear analysis in the context of Cretaceous palaeosynecology, are used to infer the mechanical properties of the foods these dinosaurs consumed. The phylliform teeth of ankylosaurs were poorly adapted for habitually processing high-fibre plant matter. Nevertheless, ankylosaur diets were likely more varied than traditionally assumed: the relatively large, bladed teeth of nodosaurids would have been better adapted to processing a tougher, more fibrous diet than the smaller, cusp-like teeth of ankylosaurids. Ankylosaur microwear is characterized by a preponderance of pits and scratches, akin to modern mixed feeders, but offers no support for interspecific dietary differences. The shearing tooth batteries of ceratopsids are much better adapted to high-fibre herbivory, attested by their scratch-dominated microwear signature. There is tentative microwear evidence to suggest differences in the feeding habits of centrosaurines and chasmosaurines, but statistical support is not significant. The tooth batteries of hadrosaurids were capable of both shearing and crushing functions, suggestive of a broad dietary range. Their microwear signal overlaps broadly with that of ankylosaurs, and suggests possible dietary differences between hadrosaurines and lambeosaurines. Tooth wear evidence further indicates that all forms considered here exhibited some degree of masticatory propaliny. Our findings reveal that tooth morphology and wear exhibit different, but complimentary, dietary signals that combine to support the hypothesis of dietary niche

The Functional and Palaeoecological Implications of Tooth Morphology and Wear for the Megaherbivorous Dinosaurs from the Dinosaur Park Formation (Upper Campanian) of Alberta, Canada

PubMed Central

Mallon, Jordan C.; Anderson, Jason S.

2014-01-01

Megaherbivorous dinosaurs were exceptionally diverse on the Late Cretaceous island continent of Laramidia, and a growing body of evidence suggests that this diversity was facilitated by dietary niche partitioning. We test this hypothesis using the fossil megaherbivore assemblage from the Dinosaur Park Formation (upper Campanian) of Alberta as a model. Comparative tooth morphology and wear, including the first use of quantitative dental microwear analysis in the context of Cretaceous palaeosynecology, are used to infer the mechanical properties of the foods these dinosaurs consumed. The phylliform teeth of ankylosaurs were poorly adapted for habitually processing high-fibre plant matter. Nevertheless, ankylosaur diets were likely more varied than traditionally assumed: the relatively large, bladed teeth of nodosaurids would have been better adapted to processing a tougher, more fibrous diet than the smaller, cusp-like teeth of ankylosaurids. Ankylosaur microwear is characterized by a preponderance of pits and scratches, akin to modern mixed feeders, but offers no support for interspecific dietary differences. The shearing tooth batteries of ceratopsids are much better adapted to high-fibre herbivory, attested by their scratch-dominated microwear signature. There is tentative microwear evidence to suggest differences in the feeding habits of centrosaurines and chasmosaurines, but statistical support is not significant. The tooth batteries of hadrosaurids were capable of both shearing and crushing functions, suggestive of a broad dietary range. Their microwear signal overlaps broadly with that of ankylosaurs, and suggests possible dietary differences between hadrosaurines and lambeosaurines. Tooth wear evidence further indicates that all forms considered here exhibited some degree of masticatory propaliny. Our findings reveal that tooth morphology and wear exhibit different, but complimentary, dietary signals that combine to support the hypothesis of dietary niche

Locomotion in ornithischian dinosaurs: an assessment using three-dimensional computational modelling.

PubMed

Maidment, Susannah C R; Bates, Karl T; Falkingham, Peter L; VanBuren, Collin; Arbour, Victoria; Barrett, Paul M

2014-08-01

Ornithischian dinosaurs were primitively bipedal with forelimbs modified for grasping, but quadrupedalism evolved in the clade on at least three occasions independently. Outside of Ornithischia, quadrupedality from bipedal ancestors has only evolved on two other occasions, making this one of the rarest locomotory transitions in tetrapod evolutionary history. The osteological and myological changes associated with these transitions have only recently been documented, and the biomechanical consequences of these changes remain to be examined. Here, we review previous approaches to understanding locomotion in extinct animals, which can be broadly split into form-function approaches using analogy based on extant animals, limb-bone scaling, and computational approaches. We then carry out the first systematic attempt to quantify changes in locomotor muscle function in bipedal and quadrupedal ornithischian dinosaurs. Using three-dimensional computational modelling of the major pelvic locomotor muscle moment arms, we examine similarities and differences among individual taxa, between quadrupedal and bipedal taxa, and among taxa representing the three major ornithischian lineages (Thyreophora, Ornithopoda, Marginocephalia). Our results suggest that the ceratopsid Chasmosaurus and the ornithopod Hypsilophodon have relatively low moment arms for most muscles and most functions, perhaps suggesting poor locomotor performance in these taxa. Quadrupeds have higher abductor moment arms than bipeds, which we suggest is due to the overall wider bodies of the quadrupeds modelled. A peak in extensor moment arms at more extended hip angles and lower medial rotator moment arms in quadrupeds than in bipeds may be due to a more columnar hindlimb and loss of medial rotation as a form of lateral limb support in quadrupeds. We are not able to identify trends in moment arm evolution across Ornithischia as a whole, suggesting that the bipedal ancestry of ornithischians did not constrain the

Mechanisms of fate decision and lineage commitment during haematopoiesis.

PubMed

Cvejic, Ana

2016-03-01

Blood stem cells need to both perpetuate themselves (self-renew) and differentiate into all mature blood cells to maintain blood formation throughout life. However, it is unclear how the underlying gene regulatory network maintains this population of self-renewing and differentiating stem cells and how it accommodates the transition from a stem cell to a mature blood cell. Our current knowledge of transcriptomes of various blood cell types has mainly been advanced by population-level analysis. However, a population of seemingly homogenous blood cells may include many distinct cell types with substantially different transcriptomes and abilities to make diverse fate decisions. Therefore, understanding the cell-intrinsic differences between individual cells is necessary for a deeper understanding of the molecular basis of their behaviour. Here we review recent single-cell studies in the haematopoietic system and their contribution to our understanding of the mechanisms governing cell fate choices and lineage commitment.

Oscillatory fluid flow induces the osteogenic lineage commitment of mesenchymal stem cells: The effect of shear stress magnitude, frequency, and duration.

PubMed

Stavenschi, Elena; Labour, Marie-Noelle; Hoey, David A

2017-04-11

A potent regulator of bone anabolism is physical loading. However, it is currently unclear whether physical stimuli such as fluid shear within the marrow cavity is sufficient to directly drive the osteogenic lineage commitment of resident mesenchymal stem cells (MSC). Therefore, the objective of the study is to employ a systematic analysis of oscillatory fluid flow (OFF) parameters predicted to occur in vivo on early MSC osteogenic responses and late stage lineage commitment. MSCs were exposed to OFF of 1Pa, 2Pa and 5Pa magnitudes at frequencies of 0.5Hz, 1Hz and 2Hz for 1h, 2h and 4h of stimulation. Our findings demonstrate that OFF elicits a positive osteogenic response in MSCs in a shear stress magnitude, frequency, and duration dependent manner that is gene specific. Based on the mRNA expression of osteogenic markers Cox2, Runx2 and Opn after short-term fluid flow stimulation, we identified that a regime of 2Pa shear magnitude and 2Hz frequency induces the most robust and reliable upregulation in osteogenic gene expression. Furthermore, long-term mechanical stimulation utilising this regime, elicits a significant increase in collagen and mineral deposition when compared to static control demonstrating that mechanical stimuli predicted within the marrow is sufficient to directly drive osteogenesis. Copyright © 2017. Published by Elsevier Ltd.

A new sauropod dinosaur from the Middle Jurassic of the United Kingdom.

PubMed

Manning, Phillip L; Egerton, Victoria M; Romano, Mike

2015-01-01

A new record of a sauropodomorph dinosaur is here described from the Middle Jurassic (Aalenian) Saltwick Formation of Whitby (Yorkshire), UK. A single caudal vertebra represents an early sauropodomorph and signifies the earliest recognised eusauropod dinosaur from the United Kingdom. The absence of pleurocoels and a narrow, dorsoventrally deep, but craniocaudally short centrum, suggests a primitive sauropodomorph. Distinct spinopostzygopophyseal laminae rise from the lateral margins of the postzygapophyses and pass caudally along what remains of the neural spine, a character unique to a subgroup of sauropods that includes Barapasaurus, Omeisaurus and other neosauropods and eusauropods. The lack of phylogenetically robust characters in sauropod caudal vertebrae usually makes it difficult to establish affinities, but the absence of mild procoely excludes this specimen from both Diplodocoidea and Lithostrotia. The vertebra cannot be further distinguished from those of a wide range of basal sauropods, cetiosaurids and basal macronarians. However, this plesiomorphic vertebra still signifies the earliest stratigraphic occurrence for a British sauropod dinosaur.

The role of Cdx2 as a lineage specific transcriptional repressor for pluripotent network during the first developmental cell lineage segregation.

PubMed

Huang, Daosheng; Guo, Guoji; Yuan, Ping; Ralston, Amy; Sun, Lingang; Huss, Mikael; Mistri, Tapan; Pinello, Luca; Ng, Huck Hui; Yuan, Guocheng; Ji, Junfeng; Rossant, Janet; Robson, Paul; Han, Xiaoping

2017-12-07

The first cellular differentiation event in mouse development leads to the formation of the blastocyst consisting of the inner cell mass (ICM) and trophectoderm (TE). The transcription factor CDX2 is required for proper TE specification, where it promotes expression of TE genes, and represses expression of Pou5f1 (OCT4). However its downstream network in the developing embryo is not fully characterized. Here, we performed high-throughput single embryo qPCR analysis in Cdx2 null embryos to identify CDX2-regulated targets in vivo. To identify genes likely to be regulated by CDX2 directly, we performed CDX2 ChIP-Seq on trophoblast stem (TS) cells. In addition, we examined the dynamics of gene expression changes using inducible CDX2 embryonic stem (ES) cells, so that we could predict which CDX2-bound genes are activated or repressed by CDX2 binding. By integrating these data with observations of chromatin modifications, we identify putative novel regulatory elements that repress gene expression in a lineage-specific manner. Interestingly, we found CDX2 binding sites within regulatory elements of key pluripotent genes such as Pou5f1 and Nanog, pointing to the existence of a novel mechanism by which CDX2 maintains repression of OCT4 in trophoblast. Our study proposes a general mechanism in regulating lineage segregation during mammalian development.

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

PubMed

Maldonado, Maricela; Luu, Rebeccah J; Ramos, Michael E P; Nam, Jin

2016-09-01

Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632. Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.

Androgynous rex - the utility of chevrons for determining the sex of crocodilians and non-avian dinosaurs.

PubMed

Erickson, Gregory M; Kristopher Lappin, A; Larson, Peter

2005-01-01

The sex of non-avian dinosaurs has been inferred on numerous occasions using a variety of anatomical criteria, but the efficacy of none has been proven. Nearly 50 years ago Romer suggested that the cranial-most or first chevron in the tails of some reptiles, including crocodilians, is sexually dimorphic. Recent work on this subject purportedly substantiated that the female first chevron articulates in a more caudal position than in males. Furthermore, it was concluded that this element is shorter in females. These phenotypic attributes theoretically provide a broader cloacal passageway for eggs by ovipositing females and a greater attachment area for male "penile retractor muscles". Because theropod dinosaurs such as Tyrannosaurus rex presumably show similar variation in chevron anatomy, the same criteria has been advocated for sexing dinosaurs. We tested the neontological model for the chevron sexual dimorphism hypothesis using a skeletonized growth series of American alligators (Alligator mississippiensis) of known sex. No statistical support for the hypothesis was found. Furthermore, analysis of a diversity of crocodilian taxa from museum collections revealed similar findings suggesting the alligator results are not taxon specific. Study of well-preserved tyrannosaurid dinosaurs in museum collections showed nearly invariant chevron positioning like that seen in crocodilians. This suggests the usefulness of chevron anatomy for sexing dinosaurs is tenuous.

Human mesenchymal stem cells - current trends and future prospective

PubMed Central

Ullah, Imran; Subbarao, Raghavendra Baregundi; Rho, Gyu Jin

2015-01-01

Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials. PMID:25797907

Scaling in Theropod Dinosaurs: Femoral Bone Dimensions

ERIC Educational Resources Information Center

Lee, Scott A.

2014-01-01

Finding topics that inspire students is an important aspect of any physics course. Virtually everyone is fascinated by "Tyrannosaurus rex," and the excitement of the class is palpable when we explore scaling effects in "T. rex" and other bipedal theropod dinosaurs as part of our discussion of mechanics and elasticity. In this…

Body temperatures in dinosaurs: what can growth curves tell us?

PubMed

Griebeler, Eva Maria

2013-01-01

To estimate the body temperature (BT) of seven dinosaurs Gillooly, Alleen, and Charnov (2006) used an equation that predicts BT from the body mass and maximum growth rate (MGR) with the latter preserved in ontogenetic growth trajectories (BT-equation). The results of these authors evidence inertial homeothermy in Dinosauria and suggest that, due to overheating, the maximum body size in Dinosauria was ultimately limited by BT. In this paper, I revisit this hypothesis of Gillooly, Alleen, and Charnov (2006). I first studied whether BTs derived from the BT-equation of today's crocodiles, birds and mammals are consistent with core temperatures of animals. Second, I applied the BT-equation to a larger number of dinosaurs than Gillooly, Alleen, and Charnov (2006) did. In particular, I estimated BT of Archaeopteryx (from two MGRs), ornithischians (two), theropods (three), prosauropods (three), and sauropods (nine). For extant species, the BT value estimated from the BT-equation was a poor estimate of an animal's core temperature. For birds, BT was always strongly overestimated and for crocodiles underestimated; for mammals the accuracy of BT was moderate. I argue that taxon-specific differences in the scaling of MGR (intercept and exponent of the regression line, log-log-transformed) and in the parameterization of the Arrhenius model both used in the BT-equation as well as ecological and evolutionary adaptations of species cause these inaccuracies. Irrespective of the found inaccuracy of BTs estimated from the BT-equation and contrary to the results of Gillooly, Alleen, and Charnov (2006) I found no increase in BT with increasing body mass across all dinosaurs (Sauropodomorpha, Sauropoda) studied. This observation questions that, due to overheating, the maximum size in Dinosauria was ultimately limited by BT. However, the general high inaccuracy of dinosaurian BTs derived from the BT-equation makes a reliable test of whether body size in dinosaurs was ultimately limited

Spermatogonial stem cell regulation and spermatogenesis

PubMed Central

Phillips, Bart T.; Gassei, Kathrin; Orwig, Kyle E.

2010-01-01

This article will provide an updated review of spermatogonial stem cells and their role in maintaining the spermatogenic lineage. Experimental tools used to study spermatogonial stem cells (SSCs) will be described, along with research using these tools to enhance our understanding of stem cell biology and spermatogenesis. Increased knowledge about the biology of SSCs improves our capacity to manipulate these cells for practical application. The chapter concludes with a discussion of future directions for fundamental investigation and practical applications of SSCs. PMID:20403877

A new mass mortality of juvenile Protoceratops and size-segregated aggregation behaviour in juvenile non-avian dinosaurs.

PubMed

Hone, David W E; Farke, Andrew A; Watabe, Mahito; Shigeru, Suzuki; Tsogtbaatar, Khishigjav

2014-01-01

Monodominant bonebeds are a relatively common occurrence for non-avian dinosaurs, and have been used to infer associative, and potentially genuinely social, behavior. Previously known assemblages are characterized as either mixed size-classes (juvenile and adult-sized specimens together) or single size-classes of individuals (only juveniles or only adult-sized individuals within the assemblage). In the latter case, it is generally unknown if these kinds of size-segregated aggregations characterize only a particular size stage or represent aggregations that happened at all size stages. Ceratopsians ("horned dinosaurs") are known from both types of assemblages. Here we describe a new specimen of the ceratopsian dinosaur Protoceratops andrewsi, Granger and Gregory 1923 from Mongolia representing an aggregation of four mid-sized juvenile animals. In conjunction with existing specimens of groups of P. andrewsi that includes size-clustered aggregations of young juveniles and adult-sized specimens, this new material provides evidence for some degree of size-clustered aggregation behaviour in Protoceratops throughout ontogeny. This continuity of size-segregated (and presumably age-clustered) aggregation is previously undocumented in non-avian dinosaurs. The juvenile group fills a key gap in the available information on aggregations in younger ceratopsians. Although we support the general hypothesis that many non-avian dinosaurs were gregarious and even social animals, we caution that evidence for sociality has been overstated and advocate a more conservative interpretation of some data of 'sociality' in dinosaurs.

No evidence for directional evolution of body mass in herbivorous theropod dinosaurs

PubMed Central

Zanno, Lindsay E.; Makovicky, Peter J.

2013-01-01

The correlation between large body size and digestive efficiency has been hypothesized to have driven trends of increasing mass in herbivorous clades by means of directional selection. Yet, to date, few studies have investigated this relationship from a phylogenetic perspective, and none, to our knowledge, with regard to trophic shifts. Here, we reconstruct body mass in the three major subclades of non-avian theropod dinosaurs whose ecomorphology is correlated with extrinsic evidence of at least facultative herbivory in the fossil record—all of which also achieve relative gigantism (more than 3000 kg). Ordinary least-squares regressions on natural log-transformed mean mass recover significant correlations between increasing mass and geological time. However, tests for directional evolution in body mass find no support for a phylogenetic trend, instead favouring passive models of trait evolution. Cross-correlation of sympatric taxa from five localities in Asia reveals that environmental influences such as differential habitat sampling and/or taphonomic filtering affect the preserved record of dinosaurian body mass in the Cretaceous. Our results are congruent with studies documenting that behavioural and/or ecological factors may mitigate the benefit of increasing mass in extant taxa, and suggest that the hypothesis can be extrapolated to herbivorous lineages across geological time scales. PMID:23193135

Hymyc1 downregulation promotes stem cell proliferation in Hydra vulgaris.

PubMed

Ambrosone, Alfredo; Marchesano, Valentina; Tino, Angela; Hobmayer, Bert; Tortiglione, Claudia

2012-01-01

Hydra is a unique model for studying the mechanisms underlying stem cell biology. The activity of the three stem cell lineages structuring its body constantly replenishes mature cells lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. In vertebrates, one of many genes that participate in regulating stem cell homeostasis is the protooncogene c-myc, which has been recently identified also in Hydra, and found expressed in the interstitial stem cell lineage. In the present paper, by developing a novel strategy of RNA interference-mediated gene silencing (RNAi) based on an enhanced uptake of small interfering RNAi (siRNA), we provide molecular and biological evidence for an unexpected function of the Hydra myc gene (Hymyc1) in the homeostasis of the interstitial stem cell lineage. We found that Hymyc1 inhibition impairs the balance between stem cell self renewal/differentiation, as shown by the accumulation of stem cell intermediate and terminal differentiation products in genetically interfered animals. The identical phenotype induced by the 10058-F4 inhibitor, a disruptor of c-Myc/Max dimerization, demonstrates the specificity of the RNAi approach. We show the kinetic and the reversible feature of Hymyc1 RNAi, together with the effects displayed on regenerating animals. Our results show the involvement of Hymyc1 in the control of interstitial stem cell dynamics, provide new clues to decipher the molecular control of the cell and tissue plasticity in Hydra, and also provide further insights into the complex myc network in higher organisms. The ability of Hydra cells to uptake double stranded RNA and to trigger a RNAi response lays the foundations of a comprehensive analysis of the RNAi response in Hydra allowing us to track back in the evolution and the origin of this process.

Hymyc1 Downregulation Promotes Stem Cell Proliferation in Hydra vulgaris

PubMed Central

Ambrosone, Alfredo; Marchesano, Valentina; Tino, Angela; Hobmayer, Bert; Tortiglione, Claudia

2012-01-01

Hydra is a unique model for studying the mechanisms underlying stem cell biology. The activity of the three stem cell lineages structuring its body constantly replenishes mature cells lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. In vertebrates, one of many genes that participate in regulating stem cell homeostasis is the protooncogene c-myc, which has been recently identified also in Hydra, and found expressed in the interstitial stem cell lineage. In the present paper, by developing a novel strategy of RNA interference-mediated gene silencing (RNAi) based on an enhanced uptake of small interfering RNAi (siRNA), we provide molecular and biological evidence for an unexpected function of the Hydra myc gene (Hymyc1) in the homeostasis of the interstitial stem cell lineage. We found that Hymyc1 inhibition impairs the balance between stem cell self renewal/differentiation, as shown by the accumulation of stem cell intermediate and terminal differentiation products in genetically interfered animals. The identical phenotype induced by the 10058-F4 inhibitor, a disruptor of c-Myc/Max dimerization, demonstrates the specificity of the RNAi approach. We show the kinetic and the reversible feature of Hymyc1 RNAi, together with the effects displayed on regenerating animals. Our results show the involvement of Hymyc1 in the control of interstitial stem cell dynamics, provide new clues to decipher the molecular control of the cell and tissue plasticity in Hydra, and also provide further insights into the complex myc network in higher organisms. The ability of Hydra cells to uptake double stranded RNA and to trigger a RNAi response lays the foundations of a comprehensive analysis of the RNAi response in Hydra allowing us to track back in the evolution and the origin of this process. PMID:22292012

New insights into non-avian dinosaur reproduction and their evolutionary and ecological implications: linking fossil evidence to allometries of extant close relatives.

PubMed

Werner, Jan; Griebeler, Eva Maria

2013-01-01

It has been hypothesized that a high reproductive output contributes to the unique gigantism in large dinosaur taxa. In order to infer more information on dinosaur reproduction, we established allometries between body mass and different reproductive traits (egg mass, clutch mass, annual clutch mass) for extant phylogenetic brackets (birds, crocodiles and tortoises) of extinct non-avian dinosaurs. Allometries were applied to nine non-avian dinosaur taxa (theropods, hadrosaurs, and sauropodomorphs) for which fossil estimates on relevant traits are currently available. We found that the reproductive traits of most dinosaurs conformed to similar-sized or scaled-up extant reptiles or birds. The reproductive traits of theropods, which are considered more bird-like, were indeed consistent with birds, while the traits of sauropodomorphs conformed better to reptiles. Reproductive traits of hadrosaurs corresponded to both reptiles and birds. Excluding Massospondyluscarinatus, all dinosaurs studied had an intermediary egg to body mass relationship to reptiles and birds. In contrast, dinosaur clutch masses fitted with either the masses predicted from allometries of birds (theropods) or to the masses of reptiles (all other taxa). Theropods studied had probably one clutch per year. For sauropodomorphs and hadrosaurs, more than one clutch per year was predicted. Contrary to current hypotheses, large dinosaurs did not have exceptionally high annual egg numbers (AEN). Independent of the extant model, the estimated dinosaur AEN did not exceed 850 eggs (75,000 kg sauropod) for any of the taxa studied. This estimated maximum is probably an overestimation due to unrealistic assumptions. According to most AEN estimations, the dinosaurs studied laid less than 200 eggs per year. Only some AEN estimates obtained for medium to large sized sauropods were higher (200-400 eggs). Our results provide new (testable) hypotheses, especially for reproductive traits that are insufficiently documented

New Insights into Non-Avian Dinosaur Reproduction and Their Evolutionary and Ecological Implications: Linking Fossil Evidence to Allometries of Extant Close Relatives

PubMed Central

Werner, Jan; Griebeler, Eva Maria

2013-01-01

It has been hypothesized that a high reproductive output contributes to the unique gigantism in large dinosaur taxa. In order to infer more information on dinosaur reproduction, we established allometries between body mass and different reproductive traits (egg mass, clutch mass, annual clutch mass) for extant phylogenetic brackets (birds, crocodiles and tortoises) of extinct non-avian dinosaurs. Allometries were applied to nine non-avian dinosaur taxa (theropods, hadrosaurs, and sauropodomorphs) for which fossil estimates on relevant traits are currently available. We found that the reproductive traits of most dinosaurs conformed to similar-sized or scaled-up extant reptiles or birds. The reproductive traits of theropods, which are considered more bird-like, were indeed consistent with birds, while the traits of sauropodomorphs conformed better to reptiles. Reproductive traits of hadrosaurs corresponded to both reptiles and birds. Excluding Massospondylus carinatus , all dinosaurs studied had an intermediary egg to body mass relationship to reptiles and birds. In contrast, dinosaur clutch masses fitted with either the masses predicted from allometries of birds (theropods) or to the masses of reptiles (all other taxa). Theropods studied had probably one clutch per year. For sauropodomorphs and hadrosaurs, more than one clutch per year was predicted. Contrary to current hypotheses, large dinosaurs did not have exceptionally high annual egg numbers (AEN). Independent of the extant model, the estimated dinosaur AEN did not exceed 850 eggs (75,000 kg sauropod) for any of the taxa studied. This estimated maximum is probably an overestimation due to unrealistic assumptions. According to most AEN estimations, the dinosaurs studied laid less than 200 eggs per year. Only some AEN estimates obtained for medium to large sized sauropods were higher (200-400 eggs). Our results provide new (testable) hypotheses, especially for reproductive traits that are insufficiently

Brg1 modulates enhancer activation in mesoderm lineage commitment

DOE PAGES

Alexander, Jeffrey M.; Hota, Swetansu K.; He, Daniel; ...

2015-03-26

The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also requiredmore » to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.« less

Bioprinting for stem cell research

PubMed Central

Tasoglu, Savas; Demirci, Utkan

2012-01-01

Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

Metric-Asaurus: Conceptualizing Scale Using Dinosaur Models

ERIC Educational Resources Information Center

Gloyna, Lisa; West, Sandra; Martin, Patti; Browning, Sandra

2010-01-01

For middle school students who have seen only pictures of dinosaurs in books, in the movies, or on the internet, trying to comprehend the size of these gargantuan animals can be difficult. This lesson provides a way for students to visualize changing scale through studying extinct organisms and to gain a deeper understanding of the history of the…

Further insights into the characterization of equine adipose tissue-derived mesenchymal stem cells.

PubMed

Raabe, Oksana; Shell, Katja; Würtz, Antonia; Reich, Christine Maria; Wenisch, Sabine; Arnhold, Stefan

2011-08-01

Adipose tissue-derived stem cells (ADSCs) represent a promising subpopulation of adult stem cells for tissue engineering applications in veterinary medicine. In this study we focused on the morphological and molecular biological properties of the ADSCs. The expression of stem cell markers Oct4, Nanog and the surface markers CD90 and CD105 were detected using RT-PCR. ADSCs showed a proliferative potential and were capable of adipogenic and osteogenic differentiation. Expression of Alkaline phosphatase (AP), phosphoprotein (SPP1), Runx2 and osteocalcin (OC) mRNA were positive in osteogenic lineages and peroxisome proliferator activated receptor (Pparγ2) mRNA was positive in adipogenic lineages. ADSCs show stem cell and surface marker profiles and differentiation characteristics that are similar to but distinct from other adult stem cells, such as bone marrow-derived mesenchymal stem cells (BM-MSCs). The availability of an easily accessible and reproducible cell source may greatly facilitate the development of stem cell based tissue engineering and therapies for regenerative equine medicine.

Lamin A/C Haploinsufficiency Modulates the Differentiation Potential of Mouse Embryonic Stem Cells

PubMed Central

Sehgal, Poonam; Chaturvedi, Pankaj; Kumaran, R. Ileng; Kumar, Satish; Parnaik, Veena K.

2013-01-01

Background Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a spectrum of genetic diseases that affect specific tissues. Most available mouse models for laminopathies recapitulate disease symptoms for muscle diseases and progerias. However, loss of human lamin A/C also has highly deleterious effects on fetal development. Hence it is important to understand the impact of lamin A/C expression levels on embryonic differentiation pathways. Methodology and Principal Findings We have investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. We initially carried out a targeted disruption of one allele of the mouse lamin A/C gene (Lmna). Undifferentiated wild-type and Lmna+/− embryonic stem cells showed similar expression of pluripotency markers and cell cycle profiles. Upon spontaneous differentiation into embryoid bodies, markers for visceral endoderm such as α-fetoprotein were highly upregulated in haploinsufficient cells. However, neuronal markers such as β-III tubulin and nestin were downregulated. Furthermore, we observed a reduction in the commitment of Lmna+/− cells into the myogenic lineage, but no discernible effects on cardiac, adipocyte or osteocyte lineages. In the next series of experiments, we derived embryonic stem cell clones expressing lamin A/C short hairpin RNA and examined their differentiation potential. These cells expressed pluripotency markers and, upon differentiation, the expression of lineage-specific markers was altered as observed with Lmna+/− embryonic stem cells. Conclusions We have observed significant effects on embryonic stem cell differentiation to visceral endoderm, neuronal and myogenic lineages upon

Piwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary

PubMed Central

Ma, Xing; Wang, Su; Do, Trieu; Song, Xiaoqing; Inaba, Mayu; Nishimoto, Yoshiya; Liu, Lu-ping; Gao, Yuan; Mao, Ying; Li, Hui; McDowell, William; Park, Jungeun; Malanowski, Kate; Peak, Allison; Perera, Anoja; Li, Hua; Gaudenz, Karin; Haug, Jeff; Yamashita, Yukiko; Lin, Haifan; Ni, Jian-quan; Xie, Ting

2014-01-01

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary. PMID:24658126

Nest substrate reflects incubation style in extant archosaurs with implications for dinosaur nesting habits.

PubMed

Tanaka, Kohei; Zelenitsky, Darla K; Therrien, François; Kobayashi, Yoshitsugu

2018-03-15

Dinosaurs thrived and reproduced in various regions worldwide, including the Arctic. In order to understand their nesting in diverse or extreme environments, the relationships between nests, nesting environments, and incubation methods in extant archosaurs were investigated. Statistical analyses reveal that species of extant covered nesters (i.e., crocodylians and megapodes) preferentially select specific sediments/substrates as a function of their nesting style and incubation heat sources. Relationships between dinosaur eggs and the sediments in which they occur reveal that hadrosaurs and some sauropods (i.e., megaloolithid eggs) built organic-rich mound nests that relied on microbial decay for incubation, whereas other sauropods (i.e., faveoloolithid eggs) built sandy in-filled hole nests that relied on solar or potentially geothermal heat for incubation. Paleogeographic distribution of mound nests and sandy in-filled hole nests in dinosaurs reveals these nest types produced sufficient incubation heat to be successful up to mid latitudes (≤47°), 10° higher than covered nesters today. However, only mound nesting and likely brooding could have produced sufficient incubation heat for nesting above the polar circle (>66°). As a result, differences in nesting styles may have placed restrictions on the reproduction of dinosaurs and their dispersal at high latitudes.

Lower limits of ornithischian dinosaur body size inferred from a new Upper Jurassic heterodontosaurid from North America

PubMed Central

Butler, Richard J.; Galton, Peter M.; Porro, Laura B.; Chiappe, Luis M.; Henderson, Donald M.; Erickson, Gregory M.

2010-01-01

The extremes of dinosaur body size have long fascinated scientists. The smallest (<1 m length) known dinosaurs are carnivorous saurischian theropods, and similarly diminutive herbivorous or omnivorous ornithischians (the other major group of dinosaurs) are unknown. We report a new ornithischian dinosaur, Fruitadens haagarorum, from the Late Jurassic of western North America that rivals the smallest theropods in size. The largest specimens of Fruitadens represent young adults in their fifth year of development and are estimated at just 65–75 cm in total body length and 0.5–0.75 kg body mass. They are thus the smallest known ornithischians. Fruitadens is a late-surviving member of the basal dinosaur clade Heterodontosauridae, and is the first member of this clade to be described from North America. The craniodental anatomy and diminutive body size of Fruitadens suggest that this taxon was an ecological generalist with an omnivorous diet, thus providing new insights into morphological and palaeoecological diversity within Dinosauria. Late-surviving (Late Jurassic and Early Cretaceous) heterodontosaurids are smaller and less ecologically specialized than Early (Late Triassic and Early Jurassic) heterodontosaurids, and this ecological generalization may account in part for the remarkable 100-million-year-long longevity of the clade. PMID:19846460

A new primitive Neornithischian dinosaur from the Jurassic of Patagonia with gut contents

NASA Astrophysics Data System (ADS)

Salgado, Leonardo; Canudo, José I.; Garrido, Alberto C.; Moreno-Azanza, Miguel; Martínez, Leandro C. A.; Coria, Rodolfo A.; Gasca, José M.

2017-02-01

We describe a new species of an ornithischian dinosaur, Isaberrysaura mollensis gen. et sp. nov. The specimen, consisting in an almost complete skull and incomplete postcranium was collected from the marine-deltaic deposits of the Los Molles Formation (Toarcian-Bajocian), being the first reported dinosaur for this unit, one of the oldest from Neuquén Basin, and the first neornithischian dinosaur known from the Jurassic of South America. Despite showing a general stegosaurian appearance, the extensive phylogenetic analysis carried out depicts Isaberrysaura mollensis gen. et sp. nov. as a basal ornithopod, suggesting that both Thyreophora and neornithischians could have achieved significant convergent features. The specimen was preserved articulated and with some of its gut content place in the middle-posterior part of the thoracic cavity. Such stomach content was identified as seeds, most of them belonging to the Cycadales group. This finding reveals a possible and unexpected role of this ornithischian species as seed-dispersal agent.

A new primitive Neornithischian dinosaur from the Jurassic of Patagonia with gut contents

PubMed Central

Salgado, Leonardo; Canudo, José I.; Garrido, Alberto C.; Moreno-Azanza, Miguel; Martínez, Leandro C. A.; Coria, Rodolfo A.; Gasca, José M.

2017-01-01

We describe a new species of an ornithischian dinosaur, Isaberrysaura mollensis gen. et sp. nov. The specimen, consisting in an almost complete skull and incomplete postcranium was collected from the marine-deltaic deposits of the Los Molles Formation (Toarcian-Bajocian), being the first reported dinosaur for this unit, one of the oldest from Neuquén Basin, and the first neornithischian dinosaur known from the Jurassic of South America. Despite showing a general stegosaurian appearance, the extensive phylogenetic analysis carried out depicts Isaberrysaura mollensis gen. et sp. nov. as a basal ornithopod, suggesting that both Thyreophora and neornithischians could have achieved significant convergent features. The specimen was preserved articulated and with some of its gut content place in the middle-posterior part of the thoracic cavity. Such stomach content was identified as seeds, most of them belonging to the Cycadales group. This finding reveals a possible and unexpected role of this ornithischian species as seed-dispersal agent. PMID:28202910

A new primitive Neornithischian dinosaur from the Jurassic of Patagonia with gut contents.

PubMed

Salgado, Leonardo; Canudo, José I; Garrido, Alberto C; Moreno-Azanza, Miguel; Martínez, Leandro C A; Coria, Rodolfo A; Gasca, José M

2017-02-16

We describe a new species of an ornithischian dinosaur, Isaberrysaura mollensis gen. et sp. nov. The specimen, consisting in an almost complete skull and incomplete postcranium was collected from the marine-deltaic deposits of the Los Molles Formation (Toarcian-Bajocian), being the first reported dinosaur for this unit, one of the oldest from Neuquén Basin, and the first neornithischian dinosaur known from the Jurassic of South America. Despite showing a general stegosaurian appearance, the extensive phylogenetic analysis carried out depicts Isaberrysaura mollensis gen. et sp. nov. as a basal ornithopod, suggesting that both Thyreophora and neornithischians could have achieved significant convergent features. The specimen was preserved articulated and with some of its gut content place in the middle-posterior part of the thoracic cavity. Such stomach content was identified as seeds, most of them belonging to the Cycadales group. This finding reveals a possible and unexpected role of this ornithischian species as seed-dispersal agent.

Stem Cells, Progenitor Cells, and Lineage Decisions in the Ovary

PubMed Central

Hummitzsch, Katja; Anderson, Richard A.; Wilhelm, Dagmar; Wu, Ji; Telfer, Evelyn E.; Russell, Darryl L.; Robertson, Sarah A.

2015-01-01

Exploring stem cells in the mammalian ovary has unleashed a Pandora's box of new insights and questions. Recent evidence supports the existence of stem cells of a number of the different cell types within the ovary. The evidence for a stem cell model producing mural granulosa cells and cumulus cells is strong, despite a limited number of reports. The recent identification of a precursor granulosa cell, the gonadal ridge epithelial-like cell, is exciting and novel. The identification of female germline (oogonial) stem cells is still very new and is currently limited to just a few species. Their origins and physiological roles, if any, are unknown, and their potential to produce oocytes and contribute to follicle formation in vivo lacks robust evidence. The precursor of thecal cells remains elusive, and more compelling data are needed. Similarly, claims of very small embryonic-like cells are also preliminary. Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed. Another important issue is the role of the stroma in guiding the formation of the ovary, ovigerous cords, follicles, and surface epithelium. Immune cells may also play key roles in developmental patterning, given their critical roles in corpora lutea formation and regression. Thus, while the cellular biology of the ovary is extremely important for its major endocrine and fertility roles, there is much still to be discovered. This review draws together the current evidence and perspectives on this topic. PMID:25541635

In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation.

PubMed

Choi, Hyun Woo; Hong, Yean Ju; Kim, Jong Soo; Song, Hyuk; Cho, Ssang Gu; Bae, Hojae; Kim, Changsung; Byun, Sung June; Do, Jeong Tae

2017-01-01

Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

Direct U-Pb dating of Cretaceous and Paleocene dinosaur bones, San Juan Basin, New Mexico: COMMENT

USGS Publications Warehouse

Koenig, Alan E.; Lucas, Spencer G.; Neymark, Leonid A.; Heckert, Andrew B.; Sullivan, Robert M.; Jasinski, Steven E.; Fowler, Denver W.

2012-01-01

Based on U-Pb dating of two dinosaur bones from the San Juan Basin of New Mexico (United States), Fassett et al. (2011) claim to provide the first successful direct dating of fossil bones and to establish the presence of Paleocene dinosaurs. Fassett et al. ignore previously published work that directly questions their stratigraphic interpretations (Lucas et al., 2009), and fail to provide sufficient descriptions of instrumental, geochronological, and statistical treatments of the data to allow evaluation of the potentially complex diagenetic and recrystallization history of bone. These shortcomings lead us to question the validity of the U-Pb dates published by Fassett et al. and their conclusions regarding the existence of Paleocene dinosaurs.

Feeding strategies as revealed by the section moduli of the humerus bones in bipedal theropod dinosaurs

NASA Astrophysics Data System (ADS)

Lee, Scott; Richards, Zachary

2015-03-01

The section modulus of a bone is a measure of its ability to resist bending torques. Carnivorous dinosaurs presumably had strong arm bones to hold struggling prey during hunting. Some theropods are believed to have become herbivorous and such animals would not have needed such strong arms. In this work, the section moduli of the humerus bones of bipedal theropod dinosaurs (from Microvenator celer to Tyrannosaurus rex) are studied to determine the maximum bending loads their arms could withstand. The results show that bending strength is not of uniform importance to these magnificent animals. The predatory theropods had strong arms for use in hunting. In contrast, the herbivorous dinosaurs had weaker arms.

Implications of ecological energetics and biophysical and developmental constraints for life history variation in dinosaurs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunham, A.E.; Overall, K.L.; Forster, C.A.

1988-01-01

There has been much recent speculation concerning the nature of life history variation in dinosaurs (Case, 1978; Bakker, 1986; Horner, 1982, 1984a). The purpose of this paper is to review the data on dinosaur life histories and to examine the nature and magnitude of the demographic and physiological factors that must have constrained life history variation in this group. 145 refs., 8 figs., 3 tabs.

Multipotent Stem Cell and Reproduction.

PubMed

Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sobhani, Aligholi

Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. The accessibility and adaptability of these amazing cells create them a great therapeutic choice for different part of medical approaches, and it becomes interesting topic in the scientific researches to found obvious method for the most advantageous use of MSC-based therapies. Recent studies in the field of stem cell biology have provided new perspectives and opportunities for the treatment of infertility disorders.

Intervertebral disc-derived stem cells: implications for regenerative medicine and neural repair.

PubMed

Erwin, W Mark; Islam, Diana; Eftekarpour, Eftekhar; Inman, Robert D; Karim, Muhammad Zia; Fehlings, Michael G

2013-02-01

An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells. To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo. Tissue repair strategies require a source of appropriate cells that could be used to replace dead or damaged cells and tissues such as stem cells. Here we examined the potential use of IVD-derived stem cells in regenerative medicine approaches and neural repair. Nonchondrodystrophic canine IVD nucleus pulposus (NP) cells were used to generate stem/progenitor cells (NP progenitor cells [NPPCs]) and the NPPCs were differentiated in vitro into chondrogenic, adipogenic, and neurogenic lineages and in vivo into the neurogenic lineage. NPPCs were compared with bone marrow-derived mesenchymal (stromal) stem cells in terms of the expression of stemness genes. The expression of the neural crest marker protein 0 and the Brachyury gene were evaluated in NP cells and NPPCs. NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD133, Nestin, and neural cell adhesion molecule but differ from mesenchymal (stromal) stem cells in the higher expression of the Nanog gene by NPPCs. NPPCs do not express protein 0 or the Brachyury gene both of which are expressed by the totality of IVD NP cells. The percentage of NPPCs within the IVD is 1% of the total as derived by colony-forming assay. NPPCs are capable of differentiating along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo within the compact myelin-deficient shiverer mouse. We propose that the IVD NP represents a regenerative niche suggesting that the IVD could represent a readily accessible source of precursor cells for neural repair and regeneration.

Hematopoietic stem cells found in lineage-positive subsets in the bone marrow of 5-fluorouracil-treated mice.

PubMed

Nishi, N; Osawa, M; Ishikawa, R; Nishikawa, M; Tsumura, H; Inoue, H; Sudo, T

1995-09-01

It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers radioprotection. To investigate this effect, we performed bone marrow transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was markedly decreased relative to those from untreated controls. These results showed that the surface characteristics of cells that contributed to this radio-protective effect differ from those of stem cells as reported recently. BM MNC of mice treated with 5-FU were separated on the basis of expression of the lineage-specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective effects such that 100% and 60% survived, respectively. Flow cytometric analysis 165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice, respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which showed radioprotective effects on a secondary irradiated host were detected from mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these findings demonstrated that stem cells expressing Lin+ present in the BM of mice treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an important role in the recovery of myeloablative mice.

PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells

PubMed Central

Juliano, Celina E.; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A.; Wessel, Gary M.; Steele, Robert E.; Lin, Haifan

2014-01-01

PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI–piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality. PMID:24367095

PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells.

PubMed

Juliano, Celina E; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A; Wessel, Gary M; Steele, Robert E; Lin, Haifan

2014-01-07

PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI-piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality.

Concomitant inhibition of prolyl hydroxylases and ROCK initiates differentiation of mesenchymal stem cells and PC12 towards the neuronal lineage.

PubMed

Pacary, Emilie; Petit, Edwige; Bernaudin, Myriam

2008-12-12

This study demonstrates that a prolyl hydroxylase inhibitor, FG-0041, is able, in combination with the ROCK inhibitor, Y-27632, to initiate differentiation of mesenchymal stem cells (MSCs) into neuron-like cells. FG-0041/Y-27632 co-treatment provokes morphological changes into neuron-like cells, increases neuronal marker expression and provokes modifications of cell cycle-related gene expression consistent with a cell cycle arrest of MSC, three events showing the engagement of MSC towards the neuronal lineage. Moreover, as we observed in our previous studies with cobalt chloride and desferroxamine, the activation of HIF-1 by this prolyl hydroxylase inhibitor is potentiated by Y-27632 which could explain at least in part the effect of this co-treatment on MSC neuronal differentiation. In addition, we show that this co-treatment enhances neurite outgrowth and tyrosine hydroxylase expression in PC12 cells. Altogether, these results evidence that concomitant inhibition of prolyl hydroxylases and ROCK represents a relevant protocol to initiate neuronal differentiation.

A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.

PubMed

Yao, Zizhen; Mich, John K; Ku, Sherman; Menon, Vilas; Krostag, Anne-Rachel; Martinez, Refugio A; Furchtgott, Leon; Mulholland, Heather; Bort, Susan; Fuqua, Margaret A; Gregor, Ben W; Hodge, Rebecca D; Jayabalu, Anu; May, Ryan C; Melton, Samuel; Nelson, Angelique M; Ngo, N Kiet; Shapovalova, Nadiya V; Shehata, Soraya I; Smith, Michael W; Tait, Leah J; Thompson, Carol L; Thomsen, Elliot R; Ye, Chaoyang; Glass, Ian A; Kaykas, Ajamete; Yao, Shuyuan; Phillips, John W; Grimley, Joshua S; Levi, Boaz P; Wang, Yanling; Ramanathan, Sharad

2017-01-05

During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/β-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace

USGS Publications Warehouse

Milner, Andrew R.C.; Harris, J.D.; Lockley, M.G.; Kirkland, J.I.; Matthews, N.A.

2009-01-01

Background: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Methodology/Principal Findings: Here we describe a well-preserved theropod trackway in a Lower Jurassic (???198 millionyear- old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. Conclusions/Significance: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace.

PubMed

Milner, Andrew R C; Harris, Jerald D; Lockley, Martin G; Kirkland, James I; Matthews, Neffra A

2009-01-01

Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

PubMed Central

Milner, Andrew R. C.; Harris, Jerald D.; Lockley, Martin G.; Kirkland, James I.; Matthews, Neffra A.

2009-01-01

Background Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Methodology/Principal Findings Here we describe a well-preserved theropod trackway in a Lower Jurassic (∼198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. Conclusions/Significance The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods. PMID:19259260

Body Temperatures in Dinosaurs: What Can Growth Curves Tell Us?

PubMed Central

Griebeler, Eva Maria

2013-01-01

To estimate the body temperature (BT) of seven dinosaurs Gillooly, Alleen, and Charnov (2006) used an equation that predicts BT from the body mass and maximum growth rate (MGR) with the latter preserved in ontogenetic growth trajectories (BT-equation). The results of these authors evidence inertial homeothermy in Dinosauria and suggest that, due to overheating, the maximum body size in Dinosauria was ultimately limited by BT. In this paper, I revisit this hypothesis of Gillooly, Alleen, and Charnov (2006). I first studied whether BTs derived from the BT-equation of today’s crocodiles, birds and mammals are consistent with core temperatures of animals. Second, I applied the BT-equation to a larger number of dinosaurs than Gillooly, Alleen, and Charnov (2006) did. In particular, I estimated BT of Archaeopteryx (from two MGRs), ornithischians (two), theropods (three), prosauropods (three), and sauropods (nine). For extant species, the BT value estimated from the BT-equation was a poor estimate of an animal’s core temperature. For birds, BT was always strongly overestimated and for crocodiles underestimated; for mammals the accuracy of BT was moderate. I argue that taxon-specific differences in the scaling of MGR (intercept and exponent of the regression line, log-log-transformed) and in the parameterization of the Arrhenius model both used in the BT-equation as well as ecological and evolutionary adaptations of species cause these inaccuracies. Irrespective of the found inaccuracy of BTs estimated from the BT-equation and contrary to the results of Gillooly, Alleen, and Charnov (2006) I found no increase in BT with increasing body mass across all dinosaurs (Sauropodomorpha, Sauropoda) studied. This observation questions that, due to overheating, the maximum size in Dinosauria was ultimately limited by BT. However, the general high inaccuracy of dinosaurian BTs derived from the BT-equation makes a reliable test of whether body size in dinosaurs was ultimately

Fossilized skin reveals coevolution with feathers and metabolism in feathered dinosaurs and early birds.

PubMed

McNamara, Maria E; Zhang, Fucheng; Kearns, Stuart L; Orr, Patrick J; Toulouse, André; Foley, Tara; Hone, David W E; Rogers, Chris S; Benton, Michael J; Johnson, Diane; Xu, Xing; Zhou, Zhonghe

2018-05-25

Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic.

Response to Comments on "Evidence for mesothermy in dinosaurs".

PubMed

Grady, John M; Enquist, Brian J; Dettweiler-Robinson, Eva; Wright, Natalie A; Smith, Felisa A

2015-05-29

D'Emic and Myhrvold raise a number of statistical and methodological issues with our recent analysis of dinosaur growth and energetics. However, their critiques and suggested improvements lack biological and statistical justification. Copyright © 2015, American Association for the Advancement of Science.

A basal dromaeosaurid and size evolution preceding avian flight.

PubMed

Turner, Alan H; Pol, Diego; Clarke, Julia A; Erickson, Gregory M; Norell, Mark A

2007-09-07

Fossil evidence for changes in dinosaurs near the lineage leading to birds and the origin of flight has been sparse. A dinosaur from Mongolia represents the basal divergence within Dromaeosauridae. The taxon's small body size and phylogenetic position imply that extreme miniaturization was ancestral for Paraves (the clade including Avialae, Troodontidae, and Dromaeosauridae), phylogenetically earlier than where flight evolution is strongly inferred. In contrast to the sustained small body sizes among avialans throughout the Cretaceous Period, the two dinosaurian lineages most closely related to birds, dromaeosaurids and troodontids, underwent four independent events of gigantism, and in some lineages size increased by nearly three orders of magnitude. Thus, change in theropod body size leading to flight's origin was not unidirectional.

Determination of osteogenic or adipogenic lineages in muscle-derived stem cells (MDSCs) by a collagen-binding peptide (CBP) derived from bone sialoprotein (BSP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin

Highlights: Black-Right-Pointing-Pointer CBP sequence is identified from BSP and has collagen binding activity. Black-Right-Pointing-Pointer CBP directly activates the MAPK signaling, especially ERK1/2. Black-Right-Pointing-Pointer CBP increase osteoblastic differentiation by the activation of Runx2. Black-Right-Pointing-Pointer CBP decrease adipogenic differentiation by the inhibition of PPAR{gamma}. -- Abstract: Bone sialoprotein (BSP) is a mineralized, tissue-specific, non-collagenous protein that is normally expressed only in mineralized tissues such as bone, dentin, cementum, and calcified cartilage, and at sites of new mineral formation. The binding of BSP to collagen is thought to be important for initiating bone mineralization and bone cell adhesion to the mineralized matrix. Severalmore » recent studies have isolated stem cells from muscle tissue, but their functional properties are still unclear. In this study, we examined the effects of a synthetic collagen-binding peptide (CBP) on the differentiation efficiency of muscle-derived stem cells (MDSCs). The CBP sequence (NGVFKYRPRYYLYKHAYFYPHLKRFPVQ) corresponds to residues 35-62 of bone sialoprotein (BSP), which are located within the collagen-binding domain in BSP. Interestingly, this synthetic CBP inhibited adipogenic differentiation but increased osteogenic differentiation in MDSCs. The CBP also induced expression of osteoblastic marker proteins, including alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx2), and osteocalcin; prevented adipogenic differentiation in MDSCs; and down-regulated adipose-specific mRNAs, such as adipocyte protein 2 (aP2) and peroxisome proliferator-activated receptor {gamma}. The CBP increased Extracellular signal-regulated kinases (ERK) 1/2 protein phosphorylation, which is important in lineage determination. These observations suggest that this CBP determines the osteogenic or adipogenic lineage in MDSCs by activating ERK1/2. Taken

Morphological Diversity and Evolution of the Jugal in Dinosaurs.

PubMed

Sullivan, Corwin; Xu, Xing

2017-01-01

In dinosaurs, as in other reptiles, the homologue of the mammalian zygomatic bone is the jugal. The dinosaurian jugal was primitively triradiate, with posterior, dorsal and anterior processes that respectively contacted the quadratojugal, the postorbital, and the maxilla and lacrimal. However, the jugal evolved along different lines in the three major dinosaurian clades. In theropods this cranial element remained relatively conservative in morphology, apart from being reduced to a rod-like structure in most birds and a few non-avians. In sauropodomorphs the jugal eventually became small, plate-like and nearly restricted to the area below the orbit, even being excluded from the ventral margin of the skull in many derived taxa. Among ornithischians the jugal was highly variable, but in many cases became large and/or adorned with ornamental features such as horns, flanges, and rugosities. The jugal does not appear to have been a site of muscle attachment in most non-avian dinosaurs, but represented an important structural element in the akinetic dinosaurian skull. The conspicuous jugal ornaments seen in many ornithischian dinosaurs, like the less striking ones documented in some saurischians, may have played an important role in the social behavior of the species that possessed them. In many cases they have a weapon-like aspect suggesting use in aggressive displays, if not actual combat, adding to the evidence that agonistic behavior was likely widespread among ornithischians in particular. Anat Rec, 300:30-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Footprints of large theropod dinosaurs and implications on the age of Triassic biotas from Southern Brazil

NASA Astrophysics Data System (ADS)

da Silva, Rafael Costa; Barboni, Ronaldo; Dutra, Tânia; Godoy, Michel Marques; Binotto, Raquel Barros

2012-11-01

Dinosaur footprints found in an outcrop of the Caturrita Formation (Rio Grande do Sul State, Southern Brazil), associated with a diverse and well preserved record of fauna and flora, reopen the debate about its exclusive Triassic age. The studied footprints were identified as Eubrontes isp. and are interpreted as having been produced by large theropod dinosaurs. The morphological characteristics and dimensions of the footprints are more derived than those commonly found in the Carnian-Norian, and are more consistent with those found during the Rhaetian-Jurassic. The trackmaker does not correspond to any type of dinosaur yet known from Triassic rocks of Brazil. Recent studies with the paleofloristic content of this unit also support a more advanced Rhaetian or even Jurassic age for this unit.

Control of stem cell fate by engineering their micro and nanoenvironment

PubMed Central

Griffin, Michelle F; Butler, Peter E; Seifalian, Alexander M; Kalaskar, Deepak M

2015-01-01

Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix (ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine. PMID:25621104

The functional origin of dinosaur bipedalism: Cumulative evidence from bipedally inclined reptiles and disinclined mammals.

PubMed

Persons, W Scott; Currie, Philip J

2017-05-07

Bipedalism is a trait basal to, and widespread among, dinosaurs. It has been previously argued that bipedalism arose in the ancestors of dinosaurs for the function of freeing the forelimbs to serve as predatory weapons. However, this argument does not explain why bipedalism was retained among numerous herbivorous groups of dinosaurs. We argue that bipedalism arose in the dinosaur line for the purpose of enhanced cursoriality. Modern facultatively bipedal lizards offer an analog for the first stages in the evolution of dinosaurian bipedalism. Many extant lizards assume a bipedal stance while attempting to flee predators at maximum speed. Bipedalism, when combined with a caudofemoralis musculature, has cursorial advantages because the caudofemoralis provides a greater source of propulsion to the hindlimbs than is generally available to the forelimbs. That cursorial advantage explains the relative abundance of cursorial facultative bipeds and obligate bipeds among fossil diapsids and the relative scarcity of either among mammals. Having lost their caudofemoralis in the Permian, perhaps in the context of adapting to a fossorial lifestyle, the mammalian line has been disinclined towards bipedalism, but, having never lost the caudofemoralis of their ancestors, cursorial avemetatarsalians (bird-line archosaurs) were naturally inclined towards bipedalism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Yan; Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guang Zhou; Li, Yuan

2011-04-15

Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined usingmore » reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.« less

The Oldest Jurassic Dinosaur: A Basal Neotheropod from the Hettangian of Great Britain.

PubMed

Martill, David M; Vidovic, Steven U; Howells, Cindy; Nudds, John R

2016-01-01

Approximately 40% of a skeleton including cranial and postcranial remains representing a new genus and species of basal neotheropod dinosaur is described. It was collected from fallen blocks from a sea cliff that exposes Late Triassic and Early Jurassic marine and quasi marine strata on the south Wales coast near the city of Cardiff. Matrix comparisons indicate that the specimen is from the lithological Jurassic part of the sequence, below the first occurrence of the index ammonite Psiloceras planorbis and above the last occurrence of the Rhaetian conodont Chirodella verecunda. Associated fauna of echinoderms and bivalves indicate that the specimen had drifted out to sea, presumably from the nearby Welsh Massif and associated islands (St David's Archipelago). Its occurrence close to the base of the Blue Lias Formation (Lower Jurassic, Hettangian) makes it the oldest known Jurassic dinosaur and it represents the first dinosaur skeleton from the Jurassic of Wales. A cladistic analysis indicates basal neotheropodan affinities, but the specimen retains plesiomorphic characters which it shares with Tawa and Daemonosaurus.

Concise Review: Conceptualizing Paralogous Stem-Cell Niches and Unfolding Bone Marrow Progenitor Cell Identities.

PubMed

Chen, Kevin G; Johnson, Kory R; McKay, Ronald D G; Robey, Pamela G

2018-01-01

Lineage commitment and differentiation of skeletal stem cells/bone marrow stromal cells (SSCs/BMSCs, often called bone marrow-derived "mesenchymal stem/stromal" cells) offer an important opportunity to study skeletal and hematopoietic diseases, and for tissue engineering and regenerative medicine. Currently, many studies in this field have relied on cell lineage tracing methods in mouse models, which have provided a significant advancement in our knowledge of skeletal and hematopoietic stem-cell niches in bone marrow (BM). However, there is a lack of agreement in numerous fundamental areas, including origins of various BM stem-cell niches, cell identities, and their physiological roles in the BM. In order to resolve these issues, we propose a new hypothesis of "paralogous" stem-cell niches (PSNs); that is, progressively altered parallel niches within an individual species throughout the life span of the organism. A putative PSN code seems to be plausible based on analysis of transcriptional signatures in two representative genes that encode Nes-GFP and leptin receptors, which are frequently used to monitor SSC lineage development in BM. Furthermore, we suggest a dynamic paralogous BM niche (PBMN) model that elucidates the coupling and uncoupling mechanisms between BM stem-cell niches and their zones of active regeneration during different developmental stages. Elucidation of these PBMNs would enable us to resolve the existing controversies, thus paving the way to achieving precision regenerative medicine and pharmaceutical applications based on these BM cell resources. Stem Cells 2018;36:11-21. © 2017 AlphaMed Press.

New Discoveries about Dinosaurs: Separating the Facts from the News.

ERIC Educational Resources Information Center

Padian, Kevin

1988-01-01

Reviews discoveries and reports of dinosaurs to help put them into paleontological perspective. Proposes that discoveries not be announced from the field, but submitted to professional evaluation and peer review before release to the public. (Author/RT)

Cancer (stem) cell differentiation: An inherent or acquired property?

PubMed

Mohr, Marieke; Zänker, Kurt S; Dittmar, Thomas

2015-12-01

There is a growing list of data indicating that cancer (stem) cells could functionally adapt foreign tissue features, such as endothelial-like cells or neuroendocrine cells, express lineage markers or could differentiate into various lineages in response to appropriate differentiation criteria. The finding that cancer (stem) cells may possess some kind of differentiation capacity poses the question whether this might be an inherent or acquired property. Cancer stem cells share stem cell characteristics and may thus possess an inherent differentiation capacity enabling the cells to respond to various differentiation stimuli. Considering the plasticity of cancer (stem) cells, even non-tumorigenic (and putatively non-differentiable) tumor cells could give rise to tumorigenic tumor stem cells, exhibiting stem cell characteristics including an inherent differentiation capacity. On the contrary, cancer (stem) cells may have acquired differentiation capacity as a consequence of a previous cell fusion event with cell types exhibiting differentiation potential and being fusogenic, such as macrophages or stem cells. Of pivotal interest in a tumor context are macrophages, which chiefly foster the chronically inflamed tumor microenvironment. Because chronically inflamed tissue is a well-known trigger for cell fusion and both macrophages and stem cells are highly fusogenic we conclude that cell fusion events between these cell types and cancer (stem) cells should frequently occur, thereby giving rise to hybrid cells exhibiting not only novel properties, like an enhanced metastatogenic phenotype, but also parental characteristics, such as differentiation capacity. Conceivably, the combination of both properties might be advantageous for metastasizing cancer (stem) cells to adapt better and faster to a foreign organ tissue environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals.

PubMed

Decotto, Eva; Spradling, Allan C

2005-10-01

The stem cell niches at the apex of Drosophila ovaries and testes have been viewed as distinct in two major respects. While both contain germline stem cells, the testis niche also contains "cyst progenitor" stem cells, which divide to produce somatic cells that encase developing germ cells. Moreover, while both niches utilize BMP signaling, the testis niche requires a key JAK/STAT signal. We now show, by lineage marking, that the ovarian niche also contains a second type of stem cell. These "escort stem cells" morphologically resemble testis cyst progenitor cells and their daughters encase developing cysts before undergoing apoptosis at the time of follicle formation. In addition, we show that JAK/STAT signaling also plays a critical role in ovarian niche function, and acts within escort cells. These observations reveal striking similarities in the stem cell niches of male and female gonads, and suggest that they are largely governed by common mechanisms.

parasitised feathered dinosaurs as revealed by Cretaceous amber assemblages.

PubMed

Peñalver, Enrique; Arillo, Antonio; Delclòs, Xavier; Peris, David; Grimaldi, David A; Anderson, Scott R; Nascimbene, Paul C; Pérez-de la Fuente, Ricardo

2017-12-12

Ticks are currently among the most prevalent blood-feeding ectoparasites, but their feeding habits and hosts in deep time have long remained speculative. Here, we report direct and indirect evidence in 99 million-year-old Cretaceous amber showing that hard ticks and ticks of the extinct new family Deinocrotonidae fed on blood from feathered dinosaurs, non-avialan or avialan excluding crown-group birds. A †Cornupalpatum burmanicum hard tick is entangled in a pennaceous feather. Two deinocrotonids described as †Deinocroton draculi gen. et sp. nov. have specialised setae from dermestid beetle larvae (hastisetae) attached to their bodies, likely indicating cohabitation in a feathered dinosaur nest. A third conspecific specimen is blood-engorged, its anatomical features suggesting that deinocrotonids fed rapidly to engorgement and had multiple gonotrophic cycles. These findings provide insight into early tick evolution and ecology, and shed light on poorly known arthropod-vertebrate interactions and potential disease transmission during the Mesozoic.

Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells.

PubMed

Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

2016-08-01

Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

NASA Astrophysics Data System (ADS)

Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

2016-08-01

Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

Distinct regulation of Snail in two muscle lineages of the ascidian embryo achieves temporal coordination of muscle development.

PubMed

Tokuoka, Miki; Kobayashi, Kenji; Satou, Yutaka

2018-06-06

The transcriptional repressor Snail is required for proper differentiation of the tail muscle of ascidian tadpole larvae. Two muscle lineages (B5.1 and B6.4) contribute to the anterior tail muscle cells, and are consecutively separated from a transcriptionally quiescent germ cell lineage at the 16- and 32-cell stages. Concomitantly, cells of these lineages begin to express Tbx6.b ( Tbx6-r.b ) at the 16- and 32-cell stages, respectively. Meanwhile, Snail expression begins in these two lineages simultaneously at the 32-cell stage. Here, we show that Snail expression is regulated differently between these two lineages. In the B5.1 lineage, Snail was activated through Tbx6.b , which is activated by maternal factors, including Zic-r.a. In the B6.4 lineage, the MAPK pathway was cell-autonomously activated by a constitutively active form of Raf, enabling Zic-r.a to activate Snail independently of Tbx6.b As a result, Snail begins to be expressed at the 32-cell stage simultaneously in these two lineages. Such shortcuts might be required for coordinating developmental programs in embryos in which cells become separated progressively from stem cells, including germline cells. © 2018. Published by The Company of Biologists Ltd.

A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians.

PubMed

März, Martin; Seebeck, Florian; Bartscherer, Kerstin

2013-11-01

In contrast to adult vertebrates, which have limited capacities for neurogenesis, adult planarians undergo constitutive cellular turnover during homeostasis and are even able to regenerate a whole brain after decapitation. This enormous plasticity derives from pluripotent stem cells residing in the planarian body in large numbers. It is still obscure how these stem cells are programmed for differentiation into specific cell lineages and how lineage identity is maintained. Here we identify a Pitx transcription factor of crucial importance for planarian regeneration. In addition to patterning defects that are co-dependent on the LIM homeobox transcription factor gene islet1, which is expressed with pitx at anterior and posterior regeneration poles, RNAi against pitx results in islet1-independent specific loss of serotonergic (SN) neurons during regeneration. Besides its expression in terminally differentiated SN neurons we found pitx in stem cell progeny committed to the SN fate. Also, intact pitx RNAi animals gradually lose SN markers, a phenotype that depends neither on increased apoptosis nor on stem cell-based turnover or transdifferentiation into other neurons. We propose that pitx is a terminal selector gene for SN neurons in planarians that controls not only their maturation but also their identity by regulating the expression of the Serotonin production and transport machinery. Finally, we made use of this function of pitx and compared the transcriptomes of regenerating planarians with and without functional SN neurons, identifying at least three new neuronal targets of Pitx.

A New Mass Mortality of Juvenile Protoceratops and Size-Segregated Aggregation Behaviour in Juvenile Non-Avian Dinosaurs

PubMed Central

Hone, David W. E.; Farke, Andrew A.; Watabe, Mahito; Shigeru, Suzuki; Tsogtbaatar, Khishigjav

2014-01-01

Background Monodominant bonebeds are a relatively common occurrence for non-avian dinosaurs, and have been used to infer associative, and potentially genuinely social, behavior. Previously known assemblages are characterized as either mixed size-classes (juvenile and adult-sized specimens together) or single size-classes of individuals (only juveniles or only adult-sized individuals within the assemblage). In the latter case, it is generally unknown if these kinds of size-segregated aggregations characterize only a particular size stage or represent aggregations that happened at all size stages. Ceratopsians (“horned dinosaurs”) are known from both types of assemblages. Methods/Principal Findings Here we describe a new specimen of the ceratopsian dinosaur Protoceratops andrewsi, Granger and Gregory 1923 from Mongolia representing an aggregation of four mid-sized juvenile animals. In conjunction with existing specimens of groups of P. andrewsi that includes size-clustered aggregations of young juveniles and adult-sized specimens, this new material provides evidence for some degree of size-clustered aggregation behaviour in Protoceratops throughout ontogeny. This continuity of size-segregated (and presumably age-clustered) aggregation is previously undocumented in non-avian dinosaurs. Conclusions The juvenile group fills a key gap in the available information on aggregations in younger ceratopsians. Although we support the general hypothesis that many non-avian dinosaurs were gregarious and even social animals, we caution that evidence for sociality has been overstated and advocate a more conservative interpretation of some data of ‘sociality’ in dinosaurs. PMID:25426957

InGen Inconsistencies: The "Dinosaurs" Of Jurassic Park May Not Be What The Corporation Claims

NASA Astrophysics Data System (ADS)

Haupt, R. J.; Traer, M. M.

2017-12-01

InGen has made and continues to make dubious claims about proprietary technology developed to clone non-avian dinosaurs for exhibition within their "Jurassic Park." Notably, there are several inconsistencies between their claims for how their technology works and what has been observed within the park. Here we investigate several of these inconsistencies in the hopes that it will push for increased transparency between corporations and academia. First, we highlight a disconnect between supposedly Jurassic amber used for dinosaur DNA extraction and the overwhelming presence of Late Cretaceous dinosaurs within the park. Further, InGen's mining operations only publicly operate in Jurassic-aged formations of the Dominican Republic, which clashes with the presence of Velociraptor and Gallimimus, known only from Mongolia. Second, the park contains seemingly full-grown adult specimens despite InGen's claims that they first successfully cloned a prehistoric animal in 1984, though there is no publicly available information as to what animal this was. That the park was nearly ready to open by 1993 precludes the presence of fully mature dinosaurs and suggests that InGen might be misrepresenting their technologies. Third, we must point out that fossil DNA denatures to the point of uselessness within thousands, not millions, of years. Additionally, the use of anuran DNA to fill in gaps from fossil dinosaurian DNA is a dubious choice given that more closely related organisms are available. Either there is an unexplained reason for this choice, or little attention has been paid to dinosaurian phylogeny by InGen geneticists. Finally, rumors of a secret InGen project to produce a dinosaur not currently known to paleontologists suggests one of two things: they were able to find DNA from a dinosaur previously unknown in the fossil record, which is highly plausible if their techniques are valid, or that InGen is able to artificially manipulate DNA to a degree far beyond what other

Factors Released from Endothelial Cells Exposed to Flow Impact Adhesion, Proliferation, and Fate Choice in the Adult Neural Stem Cell Lineage.

PubMed

Dumont, Courtney M; Piselli, Jennifer M; Kazi, Nadeem; Bowman, Evan; Li, Guoyun; Linhardt, Robert J; Temple, Sally; Dai, Guohao; Thompson, Deanna M

2017-08-15

The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-04-26

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells.

PubMed

Colamaio, Marianna; Tosti, Nadia; Puca, Francesca; Mari, Alessia; Gattordo, Rosaria; Kuzay, Yalçın; Federico, Antonella; Pepe, Anna; Sarnataro, Daniela; Ragozzino, Elvira; Raia, Maddalena; Hirata, Hidenari; Gemei, Marica; Mimori, Koshi; Del Vecchio, Luigi; Battista, Sabrina; Fusco, Alfredo

2016-10-01

Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.

Skin Stem Cells: At the Frontier Between the Laboratory and Clinical Practice. Part 1: Epidermal Stem Cells.

PubMed

Pastushenko, I; Prieto-Torres, L; Gilaberte, Y; Blanpain, C

2015-11-01

Stem cells are characterized by their ability to self-renew and differentiate into the different cell lineages of their tissue of origin. The discovery of stem cells in adult tissues, together with the description of specific markers for their isolation, has opened up new lines of investigation, expanding the horizons of biomedical research and raising new hope in the treatment of many diseases. In this article, we review in detail the main characteristics of the stem cells that produce the specialized cells of the skin (epidermal, mesenchymal, and melanocyte stem cells) and their potential implications and applications in diseases affecting the skin. Part I deals with the principal characteristics and potential applications of epidermal stem cells in dermatology. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Theropod Fauna from Southern Australia Indicates High Polar Diversity and Climate-Driven Dinosaur Provinciality

PubMed Central

Benson, Roger B. J.; Rich, Thomas H.; Vickers-Rich, Patricia; Hall, Mike

2012-01-01

The Early Cretaceous fauna of Victoria, Australia, provides unique data on the composition of high latitude southern hemisphere dinosaurs. We describe and review theropod dinosaur postcranial remains from the Aptian–Albian Otway and Strzelecki groups, based on at least 37 isolated bones, and more than 90 teeth from the Flat Rocks locality. Several specimens of medium- and large-bodied individuals (estimated up to ∼8.5 metres long) represent allosauroids. Tyrannosauroids are represented by elements indicating medium body sizes (∼3 metres long), likely including the holotype femur of Timimus hermani, and a single cervical vertebra represents a juvenile spinosaurid. Single specimens representing medium- and small-bodied theropods may be referrable to Ceratosauria, Ornithomimosauria, a basal coelurosaur, and at least three taxa within Maniraptora. Thus, nine theropod taxa may have been present. Alternatively, four distinct dorsal vertebrae indicate a minimum of four taxa. However, because most taxa are known from single bones, it is likely that small-bodied theropod diversity remains underestimated. The high abundance of allosauroids and basal coelurosaurs (including tyrannosauroids and possibly ornithomimosaurs), and the relative rarity of ceratosaurs, is strikingly dissimilar to penecontemporaneous dinosaur faunas of Africa and South America, which represent an arid, lower-latitude biome. Similarities between dinosaur faunas of Victoria and the northern continents concern the proportional representatation of higher clades, and may result from the prevailing temperate–polar climate of Australia, especially at high latitudes in Victoria, which is similar to the predominant warm–temperate climate of Laurasia, but distinct from the arid climate zone that covered extensive areas of Gondwana. Most dinosaur groups probably attained a near-cosmopolitan distribution in the Jurassic, prior to fragmentation of the Pangaean supercontinent, and some aspects of the

Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs.

PubMed

Tanaka, Kohei; Zelenitsky, Darla K; Therrien, François

2015-01-01

Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1) covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes), and 2) open nests, in which eggs are exposed in the nest and brooded (as in most birds). Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity) of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1) covered nests are likely the primitive condition for dinosaurs (and probably archosaurs), and 2) open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids) were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment. Open nests

Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs

PubMed Central

2015-01-01

Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1) covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes), and 2) open nests, in which eggs are exposed in the nest and brooded (as in most birds). Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity) of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1) covered nests are likely the primitive condition for dinosaurs (and probably archosaurs), and 2) open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids) were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment. Open nests

A new chasmosaurine from northern Laramidia expands frill disparity in ceratopsid dinosaurs.

PubMed

Ryan, Michael J; Evans, David C; Currie, Philip J; Loewen, Mark A

2014-06-01

A new taxon of chasmosaurine ceratopsid demonstrates unexpected disparity in parietosquamosal frill shape among ceratopsid dinosaurs early in their evolutionary radiation. The new taxon is described based on two apomorphic squamosals collected from approximately time equivalent (approximately 77 million years old) sections of the upper Judith River Formation, Montana, and the lower Dinosaur Park Formation of Dinosaur Provincial Park, Alberta. It is referred to Chasmosaurinae based on the inferred elongate morphology. The typical chasmosaurine squamosal forms an obtuse triangle in dorsal view that tapers towards the posterolateral corner of the frill. In the dorsal view of the new taxon, the lateral margin of the squamosal is hatchet-shaped with the posterior portion modified into a constricted narrow bar that would have supported the lateral margin of a robust parietal. The new taxon represents the oldest chasmosaurine from Canada, and the first pre-Maastrichtian ceratopsid to have been collected on both sides of the Canada-US border, with a minimum north-south range of 380 km. This squamosal morphology would have given the frill of the new taxon a unique dorsal profile that represents evolutionary experimentation in frill signalling near the origin of chasmosaurine ceratopsids and reinforces biogeographic differences between northern and southern faunal provinces in the Campanian of North America.