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Sample records for dinosaur stem lineage

  1. Rates of Dinosaur Body Mass Evolution Indicate 170 Million Years of Sustained Ecological Innovation on the Avian Stem Lineage

    PubMed Central

    Benson, Roger B. J.; Campione, Nicolás E.; Carrano, Matthew T.; Mannion, Philip D.; Sullivan, Corwin; Upchurch, Paul; Evans, David C.

    2014-01-01

    Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614–622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages. PMID:24802911

  2. Rates of dinosaur body mass evolution indicate 170 million years of sustained ecological innovation on the avian stem lineage.

    PubMed

    Benson, Roger B J; Campione, Nicolás E; Carrano, Matthew T; Mannion, Philip D; Sullivan, Corwin; Upchurch, Paul; Evans, David C

    2014-05-01

    Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614-622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages. PMID:24802911

  3. 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…

  4. 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

  5. Modelling Stem Cells Lineages with Markov Trees

    NASA Astrophysics Data System (ADS)

    Olariu, Victor; Coca, Daniel; Billings, Stephen A.; Kadirkamanathan, Visakan

    A variational Bayesian EM with smoothed probabilities algorithm for hidden Markov trees (HMT) is proposed for incomplete tree structured data. The full posterior of the HMT parameters is determined and the underflow problems associated with previous algorithms are eliminated. Example results for the prediction of the types of cells in real stem cell lineage trees are presented.

  6. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  7. The Drosophila cyst stem cell lineage

    PubMed Central

    Zoller, Richard; Schulz, Cordula

    2012-01-01

    In all animals, germline cells differentiate in intimate contact with somatic cells and interactions between germline and soma are particularly important for germline development and function. In the male gonad of Drosophila melanogaster, the developing germline cells are enclosed by somatic cyst cells. The cyst cells are derived from cyst stem cells (CySCs) of somatic origin and codifferentiate with the germline cells. The fast generation cycle and the genetic tractability of Drosophila has made the Drosophila testis an excellent model for studying both the roles of somatic cells in guiding germline development and the interdependence of two separate stem cell lineages. This review focuses on our current understanding of CySC specification, CySC self-renewing divisions, cyst cell differentiation, and soma-germline interactions. Many of the mechanisms guiding these processes in Drosophila testes are similarly essential for the development and function of tissues in other organisms, most importantly for gametogenesis in mammals. PMID:23087834

  8. Data defining markers of human neural stem cell lineage potential.

    PubMed

    Oikari, Lotta E; Okolicsanyi, Rachel K; Griffiths, Lyn R; Haupt, Larisa M

    2016-06-01

    Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in "Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination" (Oikari et al. 2015) [1]. PMID:26958640

  9. Data defining markers of human neural stem cell lineage potential

    PubMed Central

    Oikari, Lotta E.; Okolicsanyi, Rachel K.; Griffiths, Lyn R.; Haupt, Larisa M.

    2016-01-01

    Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in “Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination” (Oikari et al. 2015) [1]. PMID:26958640

  10. Identifying Adult Stem Cells Using Cre-Mediated Lineage Tracing.

    PubMed

    Carlone, Diana L

    2016-01-01

    Lineage-tracing has been used for decades to establish cell fate maps during development. Recently, with the advent of genetic lineage-tracing techniques (employing Cre-lox recombination), it has been possible to permanently mark progenitor/stem cell populations within somatic tissues. In addition, pulse-chase studies have shown that only stem cells are capable of producing labeled progeny after an extensive period of chase. This unit focuses on the protocols used to target putative adult stem cells in vivo. Using these techniques, one should be able to functionally confirm or deny the stem cell capacity of a given cell population. © 2016 by John Wiley & Sons, Inc. PMID:26840226

  11. 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

  12. Developmental origin and lineage plasticity of endogenous cardiac stem cells.

    PubMed

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

    2016-04-15

    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 andin vivofunctions 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

  13. Two subpopulations of stem cells for T cell lineage

    SciTech Connect

    Katsura, Y.; Amagai, T.; Kina, T.; Sado, T.; Nishikawa, S.

    1985-11-01

    An assay system for the stem cell that colonizes the thymus and differentiates into T cells was developed, and by using this assay system the existence of two subpopulations of stem cells for T cell lineage was clarified. Part-body-shielded and 900-R-irradiated C57BL/6 (H-2b, Thy-1.2) recipient mice, which do not require the transfer of pluripotent stem cells for their survival, were transferred with cells from B10 X Thy-1.1 (H-2b, Thy-1.1) donor mice. The reconstitution of the recipient's thymus lymphocytes was accomplished by stem cells in the donor cells and those spared in the shielded portion of the recipient that competitively colonize the thymus. Thus, the stem cell activity of donor cells can be evaluated by determining the proportion of donor-type (Thy-1.1+) cells in the recipient's thymus. Bone marrow cells were the most potent source of stem cells. By contrast, when the stem cell activity was compared between spleen and bone marrow cells of whole-body-irradiated (800 R) C57BL/6 mice reconstituted with B10 X Thy-1.1 bone marrow cells by assaying in part-body-shielded and irradiated C57BL/6 mice, the activity of these two organs showed quite a different time course of development. The results strongly suggest that the stem cells for T cell lineage in the bone marrow comprise at least two subpopulations, spleen-seeking and bone marrow-seeking cells.

  14. Trophoblast lineage cells derived from human induced pluripotent stem cells

    SciTech Connect

    Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard; Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  15. Mechanically induced osteogenic lineage commitment of stem cells

    PubMed Central

    2013-01-01

    Bones adapt to accommodate the physical forces they experience through changes in architecture and mass. Stem cells differentiate into bone-forming osteoblasts, and mechanical stimulation is involved in this process. Various studies have applied controlled mechanical stimulation to stem cells and investigated the effects on osteogenic lineage commitment. These studies demonstrate that physical stimuli can induce osteogenic lineage commitment. Tension, fluid shear stress, substrate material properties, and cell shape are all factors that influence osteogenic differentiation. In particular, the level of tension is important. Also, rigid substrates with stiffness similar to collagenous bone induce osteogenic differentiation, while softer substrates induce other lineages. Finally, cells allowed to adhere over a larger area are able to differentiate towards the osteogenic lineage while cells adhering to a smaller area are restricted to the adipogenic lineage. Stem cells are able to sense their mechanical environments through various mechanosensors, including the cytoskeleton, focal adhesions, and primary cilia. The cytoskeleton provides a structural frame for the cell, and myosin interacts with actin to generate cytoskeletal tension, which is important for mechanically induced osteogenesis of stem cells. Adapter proteins link the cytoskeleton to integrins, which attach the cell to the substrate, forming a focal adhesion. A variety of signaling proteins are also associated with focal adhesions. Forces are transmitted to the substrate at these sites, and an intact focal adhesion is important for mechanically induced osteogenesis. The primary cilium is a single, immotile, antenna-like structure that extends from the cell into the extracellular space. It has emerged as an important signaling center, acting as a microdomain to facilitate biochemical signaling. Mechanotransduction is the process by which physical stimuli are converted into biochemical responses. When potential mechanosensors are disrupted, the activities of components of mechanotransduction pathways are also inhibited, preventing mechanically induced osteogenesis. Calcium, mitogen-activated protein kinase/extracellular signal-regulated kinase, Wnt, Yes-associated protein/transcriptional coactivator with PDZ-binding motif and RhoA/Rho kinase signaling are some of the mechanotransduction pathways proposed to be important. In this review, types of mechanical stimuli, mechanosensors, and key pathways involved in mechanically induced osteogenesis of stem cells are discussed. PMID:24004875

  16. Methods to Assess Stem Cell Lineage, Fate and Function

    PubMed Central

    Nguyen, Patricia K.; Nag, Divya; Wu, Joseph C.

    2011-01-01

    Stem cell therapy has the potential to regenerate injured tissue. For stem cells to achieve their full therapeutic potential, stem cells must differentiate into the target cell, reach the site of injury, survive, and engraft. To fully characterize these cells, evaluation of cell morphology, lineage specific markers, cell specific function, and gene expression must be performed. To monitor survival and engraftment, cell fate imaging is vital. Only then can organ specific function be evaluated to determine the effectiveness of therapy. In this review, we will discuss methods for evaluating the function of transplanted cells for restoring the heart, nervous system, and pancreas. We will also highlight the specific challenges facing these potential therapeutic areas. PMID:20816906

  17. Adult stem cell lineage tracing and deep tissue imaging.

    PubMed

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

    2015-12-01

    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

  18. 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

  19. Hematopoietic stem cell-independent B-1a lineage.

    PubMed

    Ghosn, Eliver Eid Bou; Yang, Yang

    2015-12-01

    The accepted dogma has been that a single long-term hematopoietic stem cell (LT-HSC) can reconstitute all components of the immune system. However, our single-cell transfer studies have shown that highly purified LT-HSCs selectively fail to reconstitute B-1a cells in otherwise fully reconstituted hosts (i.e., LT-HSCs fully reconstitute follicular, marginal zone, and B-1b B cells, but not B-1a cells). These results suggest that B-1a cells are a separate B cell lineage that develops independently of classical LT-HSCs. We provide an evolutionary two-pathway development model (HSC independent versus HSC dependent), and suggest that this lineage separation is employed not only by B cells but by all hematopoietic lineages. Collectively, these findings challenge the current notion that LT-HSCs can reconstitute all components of the immune system and raise key questions about human HSC transplantation. We discuss the implications of these findings in light of our recent studies demonstrating the ability of B-1a cells to elicit antigen-specific responses that differ markedly from those mounted by follicular B cells. These findings have implications for vaccine development, in particular vaccines that may elicit the B-1a repertoire. PMID:26662720

  20. Differentiation of Neural Lineage Cells from Human Pluripotent Stem Cells

    PubMed Central

    Schwartz, Philip H.; Brick, David J.; Stover, Alexander E.; Loring, Jeanne F.; Müller, Franz Josef

    2008-01-01

    Human pluripotent stem cells have the unique properties of being able to proliferate indefinitely in their undifferentiated state and to differentiate into any somatic cell type. These cells are thus posited to be extremely useful for furthering our understanding of both normal and abnormal human development, providing a human cell preparation that can be used to screen for new reagents or therapeutic agents, and generating large numbers of differentiated cells that can be used for transplantation purposes. Critical among the applications for the latter are diseases and injuries of the nervous system, medical approaches to which have been, to date, primarily palliative in nature. Differentiation of human pluripotent stem cells into cells of the neural lineage, therefore, has become a central focus of a number of laboratories. This has resulted in the description in the literature of several dozen methods for neural cell differentiation from human pluripotent stem cells. Among these are methods for the generation of such divergent neural cells as dopaminergic neurons, retinal neurons, ventral motoneurons, and oligodendroglial progenitors. In this review, we attempt to fully describe most of these methods, breaking them down into five basic subdivisions: 1) starting material, 2) induction of loss of pluripotency, 3) neural induction, 4) neural maintenance and expansion, and 5) neuronal/glial differentiation. We also show data supporting the concept that undifferentiated human pluripotent stem cells appear to have an innate neural differentiation potential. In addition, we evaluate data comparing and contrasting neural stem cells differentiated from human pluripotent stem cells with those derived directly from the human brain. PMID:18593611

  1. Latent tri-lineage potential of adult hippocampal neural stem cells revealed by Nf1 inactivation.

    PubMed

    Sun, Gerald J; Zhou, Yi; Ito, Shiori; Bonaguidi, Michael A; Stein-O'Brien, Genevieve; Kawasaki, Nicholas K; Modak, Nikhil; Zhu, Yuan; Ming, Guo-li; Song, Hongjun

    2015-12-01

    Endogenous neural stem cells (NSCs) in the adult hippocampus are considered to be bi-potent, as they only produce neurons and astrocytes in vivo. In mouse, we found that inactivation of neurofibromin 1 (Nf1), a gene mutated in neurofibromatosis type 1, unlocked a latent oligodendrocyte lineage potential to produce all three lineages from NSCs in vivo. Our results suggest an avenue for promoting stem cell plasticity by targeting barriers of latent lineage potential. PMID:26523645

  2. Concise Review: Chemical Approaches for Modulating Lineage-Specific Stem Cells and Progenitors

    PubMed Central

    Xu, Tao; Zhang, Mingliang; Laurent, Timothy; Xie, Min

    2013-01-01

    Generation and manipulation of lineage-restricted stem and progenitor cells in vitro and/or in vivo are critical for the development of stem cell-based clinical therapeutics. Lineage-restricted stem and progenitor cells have many advantageous qualities, including being able to efficiently engraft and differentiate into desirable cell types in vivo after transplantation, and they are much less tumorigenic than pluripotent cells. Generation of lineage-restricted stem and progenitor cells can be achieved by directed differentiation from pluripotent stem cells or lineage conversion from easily obtained somatic cells. Small molecules can be very helpful in these processes since they offer several important benefits. For example, the risk of tumorigenesis is greatly reduced when small molecules are used to replace integrated transcription factors, which are widely used in cell fate conversion. Furthermore, small molecules are relatively easy to apply, optimize, and manufacture, and they can more readily be developed into conventional pharmaceuticals. Alternatively, small molecules can be used to expand or selectively control the differentiation of lineage-restricted stem and progenitor cells for desirable therapeutics purposes in vitro or in vivo. Here we summarize recent progress in the use of small molecules for the expansion and generation of desirable lineage-restricted stem and progenitor cells in vitro and for selectively controlling cell fate of lineage-restricted stem and progenitor cells in vivo, thereby facilitating stem cell-based clinical applications. PMID:23580542

  3. Differentiation in Stem Cell Lineages and in Life: Explorations in the Male Germ Line Stem Cell Lineage.

    PubMed

    Fuller, Margaret T

    2016-01-01

    I have been privileged to work on cellular differentiation during a great surge of discovery that has revealed the molecular mechanisms and genetic regulatory circuitry that control embryonic development and adult tissue maintenance and repair. Studying the regulation of proliferation and differentiation in the male germ line stem cell lineage has allowed us investigate how the developmental program imposes layers of additional controls on fundamental cellular processes like cell cycle progression and gene expression to give rise to the huge variety of specialized cell types in our bodies. We are beginning to understand how local signals from somatic support cells specify self-renewal versus differentiation in the stem cell niche at the apical tip of the testis. We are discovering the molecular events that block cell proliferation and initiate terminal differentiation at the switch from mitosis to meiosis-a signature event of the germ cell program. Our work is beginning to reveal how the developmental program that sets up the dramatic new cell type-specific transcription program that prepares germ cells for meiotic division and spermatid differentiation is turned on when cells become spermatocytes. I have had the privilege of working with incredible students, postdocs, and colleagues who have discovered, brainstormed, challenged, and refined our science and our ideas of how developmental pathways and cellular mechanisms work together to drive differentiation. PMID:26970629

  4. 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…

  5. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

    SciTech Connect

    Morizane, Ryuji; Monkawa, Toshiaki; Itoh, Hiroshi

    2009-12-25

    Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

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

    PubMed

    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

    2015-05-21

    Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, 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, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-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

  7. 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

  8. 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

  9. Is lineage decision-making restricted during tumoral reprograming of haematopoietic stem cells?

    PubMed Central

    2015-01-01

    Within the past years there have been substantial changes to our understanding of haematopoiesis and cells that initiate and sustain leukemia. Recent studies have revealed that developing haematopoietic stem and progenitor cells are much more heterogeneous and versatile than has been previously thought. This versatility includes cells using more than one route to a fate and cells having progressed some way towards a cell type retaining other lineage options as clandestine. These notions impact substantially on our understanding of the origin and nature of leukemia. An important question is whether leukemia stem cells are as versatile as their cell of origin as an abundance of cells belonging to a lineage is often a feature of overt leukemia. In this regard, we examine the coming of age of the “leukemia stem cell” theory and the notion that leukemia, like normal haematopoiesis, is a hierarchically organized tissue. We examine evidence to support the notion that whilst cells that initiate leukemia have multi-lineage potential, leukemia stem cells are reprogrammed by further oncogenic insults to restrict their lineage decision-making. Accordingly, evolution of a sub-clone of lineage-restricted malignant cells is a key feature of overt leukemia. PMID:26498146

  10. Stem cells primed for action: polycomb repressive complexes restrain the expression of lineage-specific regulators in embryonic stem cells.

    PubMed

    Jørgensen, Helle F; Giadrossi, Sara; Casanova, Miguel; Endoh, Mitsuhiro; Koseki, Haruhiko; Brockdorff, Neil; Fisher, Amanda G

    2006-07-01

    Stem cells are characterised by a capacity to self renew and generate progeny capable of differentiating along several defined lineage paths. Embryonic Stem (ES) cells are derived from the inner cell mass (ICM) of early-stage embryos and can contribute to all tissues of the developing embryo. Discovering how ES cell pluripotency and lineage induction is achieved is important for understanding normal development and for successfully applying stem cell-based therapies. A series of recent studies have shown that the chromatin profile of ES cells is unusual and have revealed a critical role for the Polycomb Repressive Complexes (PRCs) in maintaining pluripotency. In human and mouse ES cells many genes that encode transcription factors that are required for lineage specification bind PRC2 and carry bivalent (or opposing) histone signatures, being enriched for conventional indicators of active chromatin such as acetylated H3K9 and methylated H3K4, while lying within domains of repressive trimethylated H3K27. Mutant ES cells that lack H3K27 methylation inappropriately expressed these genes showing that PRC2 represses lineage-specific gene programs in ES cells. Here we discuss the implications of these new discoveries and explore the interdependence of PRC1 and PRC2 in regulating lineage-specific gene expression in ES cells. PMID:16855402

  11. Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage

    PubMed Central

    Jackson, Steven A.; Olufs, Zachariah P.G.; Tran, Khoa A.; Zaidan, Nur Zafirah; Sridharan, Rupa

    2016-01-01

    Summary During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expressed stabilization markers, had upregulated several cell cycle genes; and were transgene independent. Inhibition of DOT1L activity enhanced both the numbers of NANOG+ and NANOG+E-cadherin+ colonies in neural stem cells. Expressing SOX2 in MEFs prior to reprogramming did not alter the ratio of NANOG colonies that express E-cadherin. Taken together these results provide a unique pathway for reprogramming taken by cells of the neural lineage. PMID:26905202

  12. Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage.

    PubMed

    Jackson, Steven A; Olufs, Zachariah P G; Tran, Khoa A; Zaidan, Nur Zafirah; Sridharan, Rupa

    2016-03-01

    During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expressed stabilization markers, had upregulated several cell cycle genes; and were transgene independent. Inhibition of DOT1L activity enhanced both the numbers of NANOG+ and NANOG+E-cadherin+ colonies in neural stem cells. Expressing SOX2 in MEFs prior to reprogramming did not alter the ratio of NANOG colonies that express E-cadherin. Taken together these results provide a unique pathway for reprogramming taken by cells of the neural lineage. PMID:26905202

  13. Dinosaur Systematics

    NASA Astrophysics Data System (ADS)

    Carpenter, Kenneth; Currie, Philip J.

    1992-07-01

    In recent years dinosaurs have captured the attention of the public at an unprecedented level. At the heart of this resurgence in popular interest is an increased level of research activity, much of which is innovative in the field of paleontology. For instance, whereas earlier paleontological studies emphasized basic morphologic description and taxonomic classification, modern studies attempt to examine the role and nature of dinosaurs as living animals. More than ever before, we understand how these extinct species functioned, behaved, interacted with each other and the environment, and evolved. Nevertheless, these studies rely on certain basic building blocks of knowledge, including facts about dinosaur anatomy and taxonomic relationships. One of the purposes of this volume is to unravel some of the problems surrounding dinosaur systematics and to increase our understanding of dinosaurs as a biological species. Dinosaur Systematics presents a current overview of dinosaur systematics using various examples to explore what is a species in a dinosaur, what separates genders in dinosaurs, what morphological changes occur with maturation of a species, and what morphological variations occur within a species.

  14. Vertebrate Neural Stem Cell Segmentation, Tracking and Lineaging with Validation and Editing

    PubMed Central

    Winter, Mark; Wait, Eric; Roysam, Badri; Goderie, Susan; Ali, Rania Ahmed Naguib; Kokovay, Erzsebet; Temple, Sally; Cohen, Andrew R.

    2012-01-01

    This protocol and the accompanying software program called LEVER enable quantitative automated analysis of phase contrast time-lapse images of cultured neural stem cells. Images are captured at 5 min. intervals over a period of 5 to 15 days as the cells proliferate and differentiate. LEVER automatically segments, tracks and generates lineage trees of the stem cells from the image sequence. In addition to generating lineage trees capturing the population dynamics of clonal development, LEVER extracts quantitative phenotypic measurements of cell location, shape, movement, and size. When available, the system can include biomolecular markers imaged using fluorescence. It then displays the results to the user for highly efficient inspection and editing to correct any errors in the segmentation, tracking or lineaging. In order to enable high-throughput inspection, LEVER incorporates features for rapid identification of errors, and learning from user-supplied corrections to automatically identify and correct related errors. PMID:22094730

  15. SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.

    PubMed

    Eroglu, Elif; Burkard, Thomas R; Jiang, Yanrui; Saini, Nidhi; Homem, Catarina C F; Reichert, Heinrich; Knoblich, Juergen A

    2014-03-13

    Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation. We identify the Prdm protein Hamlet as a key component of this program. Hamlet is directly induced by Osa and regulates the progression of progenitors through distinct transcriptional states to limit the number of transit-amplifying divisions. Our data provide a mechanistic explanation for the widespread tumor suppressor activity of SWI/SNF. Because the Hamlet homologs Evi1 and Prdm16 are frequently mutated in cancer, this mechanism could well be conserved in human stem cell lineages. PAPERCLIP: PMID:24630726

  16. 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

  17. Graphene Oxide promotes embryonic stem cell differentiation to haematopoietic lineage.

    PubMed

    Garcia-Alegria, Eva; Iluit, Maria; Stefanska, Monika; Silva, Claudio; Heeg, Sebastian; Kimber, Susan J; Kouskoff, Valerie; Lacaud, Georges; Vijayaraghavan, Aravind; Batta, Kiran

    2016-01-01

    Pluripotent stem cells represent a promising source of differentiated tissue-specific stem and multipotent progenitor cells for regenerative medicine and drug testing. The realisation of this potential relies on the establishment of robust and reproducible protocols of differentiation. Several reports have highlighted the importance of biomaterials in assisting directed differentiation. Graphene oxide (GO) is a novel material that has attracted increasing interest in the field of biomedicine. In this study, we demonstrate that GO coated substrates significantly enhance the differentiation of mouse embryonic stem (ES) cells to both primitive and definitive haematopoietic cells. GO does not affect cell proliferation or survival of differentiated cells but rather enhances the transition of haemangioblasts to haemogenic endothelial cells, a key step during haematopoietic specification. Importantly, GO also improves, in addition to murine, human ES cell differentiation to blood cells. Taken together, our study reveals a positive role for GO in haematopoietic differentiation and suggests that further functionalization of GO could represent a valid strategy for the generation of large numbers of functional blood cells. Producing these cells would accelerate haematopoietic drug toxicity testing and treatment of patients with blood disorders or malignancies. PMID:27197878

  18. Dinosaur Tracking.

    ERIC Educational Resources Information Center

    Lockley, Martin

    1984-01-01

    Describes paleontological studies of trace fossils (the impressions that record the animal's activity) such as dinosaur footprints. Discusses the importance of findings to our knowledge of dinosaur social behavior and community structure. Also tracts evolution of behavior from the Upper Triassic through the Upper Cretaceous, building evidence of…

  19. Dinosaur evolution. Sustained miniaturization and anatomical innovation in the dinosaurian ancestors of birds.

    PubMed

    Lee, Michael S Y; Cau, Andrea; Naish, Darren; Dyke, Gareth J

    2014-08-01

    Recent discoveries have highlighted the dramatic evolutionary transformation of massive, ground-dwelling theropod dinosaurs into light, volant birds. Here, we apply Bayesian approaches (originally developed for inferring geographic spread and rates of molecular evolution in viruses) in a different context: to infer size changes and rates of anatomical innovation (across up to 1549 skeletal characters) in fossils. These approaches identify two drivers underlying the dinosaur-bird transition. The theropod lineage directly ancestral to birds undergoes sustained miniaturization across 50 million years and at least 12 consecutive branches (internodes) and evolves skeletal adaptations four times faster than other dinosaurs. The distinct, prolonged phase of miniaturization along the bird stem would have facilitated the evolution of many novelties associated with small body size, such as reorientation of body mass, increased aerial ability, and paedomorphic skulls with reduced snouts but enlarged eyes and brains. PMID:25082702

  20. Rewiring mesenchymal stem cell lineage specification by switching the biophysical microenvironment

    NASA Astrophysics Data System (ADS)

    Lee, Junmin; Abdeen, Amr A.; Kilian, Kristopher A.

    2014-06-01

    The propensity of stem cells to specify and commit to a particular lineage program is guided by dynamic biophysical and biochemical signals that are temporally regulated. However, most in vitro studies rely on ``snapshots'' of cell state under static conditions. Here we asked whether changing the biophysical aspects of the substrate could modulate the degree of mesenchymal stem cell (MSC) lineage specification. We chose to explore two diverse differentiation outcomes: MSC osteogenesis and trans-differentiation to neuron-like cells. MSCs were cultured on soft (~0.5 kPa) or stiff (~40 kPa) hydrogels followed by transfer to gels of the opposite stiffness. MSCs on soft gels express elevated neurogenesis markers while MSCs on stiff substrates express elevated osteogenesis markers. Transfer of MSCs from soft to stiff or stiff to soft substrates led to a switch in lineage specification. However, MSCs transferred from stiff to soft substrates maintained elevated osteogenesis markers, suggesting a degree of irreversible activation. Transferring MSCs to micropatterned substrates reveal geometric cues that further modulate lineage reversal. Taken together, this study demonstrates that MSCs remain susceptible to the biophysical properties of the extracellular matrix--even after several weeks of culture--and can redirect lineage specification in response to changes in the microenvironment.

  1. Lineage Relationship of Direct-Developing Melanocytes and Melanocyte Stem Cells in the Zebrafish

    PubMed Central

    Tryon, Robert C.; Higdon, Charles W.; Johnson, Stephen L.

    2011-01-01

    Previous research in zebrafish has demonstrated that embryonic and larval regeneration melanocytes are derived from separate lineages. The embryonic melanocytes that establish the larval pigment pattern do not require regulative melanocyte stem cell (MSC) precursors, and are termed direct-developing melanocytes. In contrast, the larval regeneration melanocytes that restore the pigment pattern after ablation develop from MSC precursors. Here, we explore whether embryonic melanocytes and MSCs share bipotent progenitors. Furthermore, we explore when fate segregation of embryonic melanocytes and MSCs occurs in zebrafish development. In order to achieve this, we develop and apply a novel lineage tracing method. We first demonstrate that Tol2-mediated genomic integration of reporter constructs from plasmids injected at the 12 cell stage occurs most frequently after the midblastula transition but prior to shield stage, between 3 and 6 hours post-fertilization. This previously uncharacterized timing of Tol2-mediated genomic integration establishes Tol2-mediated transposition as a means for conducting lineage tracing in zebrafish. Combining the Tol2-mediated lineage tracing strategy with a melanocyte regeneration assay previously developed in our lab, we find that embryonic melanocytes and larval regeneration melanocytes are derived from progenitors that contribute to both lineages. We estimate 5060 such bipotent melanogenic progenitors to be present in the shield-stage embryo. Furthermore, our examination of direct-developing and MSC-restricted lineages suggests that these are segregated from bipotent precursors after the shield stage, but prior to the end of convergence and extension. Following this early fate segregation, we estimate approximately 100 embryonic melanocyte and 90 MSC-restricted lineages are generated to establish or regenerate the zebrafish larval pigment pattern, respectively. Thus, the dual strategies of direct-development and MSC-derived development are established in the early gastrula, via fate segregation of the two lineages. PMID:21698209

  2. Conversion of embryonic stem cells into extraembryonic lineages by CRISPR-mediated activators.

    PubMed

    Wei, Shu; Zou, Qingjian; Lai, Sisi; Zhang, Quanjun; Li, Li; Yan, Quanmei; Zhou, Xiaoqing; Zhong, Huilin; Lai, Liangxue

    2016-01-01

    The recently emerged CRISPR/Cas9 technique has opened a new perspective on readily editing specific genes. When combined with transcription activators, it can precisely manipulate endogenous gene expression. Here, we enhanced the expression of endogenous Cdx2 and Gata6 genes by CRISPR-mediated activators, thus mouse embryonic stem cells (ESCs) were directly converted into two extraembryonic lineages, i.e., typical trophoblast stem cells (TSCs) and extraembryonic endoderm cells (XENCs), which exhibited characters of TSC or XENC derived from the blastocyst extraembryonic lineages such as cell morphology, specific gene expression, and differentiation ability in vitro and in vivo. This study demonstrates that the cell fate can be effectively manipulated by directly activating of specific endogenous gene expression with CRISPR-mediated activator. PMID:26782778

  3. Conversion of embryonic stem cells into extraembryonic lineages by CRISPR-mediated activators

    PubMed Central

    Wei, Shu; Zou, Qingjian; Lai, Sisi; Zhang, Quanjun; Li, Li; Yan, Quanmei; Zhou, Xiaoqing; Zhong, Huilin; Lai, Liangxue

    2016-01-01

    The recently emerged CRISPR/Cas9 technique has opened a new perspective on readily editing specific genes. When combined with transcription activators, it can precisely manipulate endogenous gene expression. Here, we enhanced the expression of endogenous Cdx2 and Gata6 genes by CRISPR-mediated activators, thus mouse embryonic stem cells (ESCs) were directly converted into two extraembryonic lineages, i.e., typical trophoblast stem cells (TSCs) and extraembryonic endoderm cells (XENCs), which exhibited characters of TSC or XENC derived from the blastocyst extraembryonic lineages such as cell morphology, specific gene expression, and differentiation ability in vitro and in vivo. This study demonstrates that the cell fate can be effectively manipulated by directly activating of specific endogenous gene expression with CRISPR-mediated activator. PMID:26782778

  4. 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

  5. Genetic Mosaic Analysis of Stem Cell Lineages in the Drosophila Ovary.

    PubMed

    Laws, Kaitlin M; Drummond-Barbosa, Daniela

    2015-01-01

    Genetic mosaic analyses represent an invaluable approach for the study of stem cell lineages in the Drosophila ovary. The generation of readily identifiable, homozygous mutant cells in the context of wild-type ovarian tissues within intact organisms allows the pinpointing of cellular requirements for gene function, which is particularly important for understanding the physiological control of stem cells and their progeny. Here, we provide a step-by-step guide to the generation and analysis of genetically mosaic ovaries using flippase (FLP)/FLP recognition target (FRT)-mediated recombination in adult Drosophila melanogaster, with a focus on the processes of oogenesis that are controlled by diet-dependent factors. PMID:26324429

  6. Changes in glycosaminoglycan structure on differentiation of human embryonic stem cells towards mesoderm and endoderm lineages

    PubMed Central

    Gasimli, Leyla; Hickey, Anne M.; Yang, Bo; Li, Guoyun; Rosa, Mitche dela; Nairn, Alison V.; Kulik, Michael J.; Dordick, Jonathan S.; Moremen, Kelley W.; Dalton, Stephen; Linhardt, Robert J.

    2014-01-01

    Background Proteoglycans are found on the cell surface and in the extracellular matrix, and serve as prime sites for interaction with signaling molecules. Proteoglycans help regulate pathways that control stem cell fate, and therefore represent an excellent tool to manipulate these pathways. Despite their importance, there is a dearth of data linking glycosaminoglycan structure within proteoglycans with stem cell differentiation. Methods Human embryonic stem cell line WA09 (H9) was differentiated into early mesoderm and endoderm lineages, and the glycosaminoglycanomic changes accompanying these transitions were studied using transcript analysis, immunoblotting, immunofluorescence and disaccharide analysis. Results Pluripotent H9 cell lumican had no glycosaminoglycan chains whereas in splanchnic mesoderm lumican was glycosaminoglycanated. H9 cells have primarily non-sulfated heparan sulfate chains. On differentiation towards splanchnic mesoderm and hepatic lineages N-sulfo group content increases. Differences in transcript expression of NDST1, HS6ST2 and HS6ST3, three heparan sulfate biosynthetic enzymes, within splanchnic mesoderm cells compared to H9 cells correlate to changes in glycosaminoglycan structure. Conclusions Differentiation of embryonic stem cells markedly change the proteoglycanome General Significance The glycosaminoglycan biosynthetic pathway is complex and highly regulated, and therefore, understanding the details of this pathway should enable better control with the aim of directing stem cell differentiation. PMID:24412195

  7. 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. PMID:20040488

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

    PubMed Central

    Pearson, Bret J.; Alvarado, Alejandro Snchez

    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. PMID:20040488

  9. Heterogeneous lineage marker expression in naive embryonic stem cells is mostly due to spontaneous differentiation

    PubMed Central

    Nair, Gautham; Abranches, Elsa; Guedes, Ana M. V.; Henrique, Domingos; Raj, Arjun

    2015-01-01

    Populations of cultured mouse embryonic stem cells (ESCs) exhibit a subfraction of cells expressing uncharacteristically low levels of pluripotency markers such as Nanog. Yet, the extent to which individual Nanog-negative cells are differentiated, both from ESCs and from each other, remains unclear. Here, we show the transcriptome of Nanog-negative cells exhibits expression of classes of genes associated with differentiation that are not yet active in cells exposed to differentiation conditions for one day. Long non-coding RNAs, however, exhibit more changes in expression in the one-day-differentiated cells than in Nanog-negative cells. These results are consistent with the concept that Nanog-negative cells may contain subpopulations of both lineage-primed and differentiated cells. Single cell analysis showed that Nanog-negative cells display substantial and coherent heterogeneity in lineage marker expression in progressively nested subsets of cells exhibiting low levels of Nanog, then low levels of Oct4, and then a set of lineage markers, which express intensely in a small subset of these more differentiated cells. Our results suggest that the observed enrichment of lineage-specific marker gene expression in Nanog-negative cells is associated with spontaneous differentiation of a subset of these cells rather than the more random expression that may be associated with reversible lineage priming. PMID:26292941

  10. Hematopoietic and mesenchymal stem cells: polymeric nanoparticle uptake and lineage differentiation

    PubMed Central

    Brüstle, Ivonne; Simmet, Thomas; Nienhaus, Gerd Ulrich; Landfester, Katharina

    2015-01-01

    Summary The combination of stem cell therapy and nanoparticles promises to enhance the effect of cellular therapies by using nanocarriers as drug delivery devices to guide the further differentiation or homing of stem cells. The impact of nanoparticles on primary cell types remains much more elusive as most groups study the nanoparticle–cell interaction in malignant cell lines. Here, we report on the influence of polymeric nanoparticles on human hematopoietic stem cells (hHSCs) and mesenchymal stem cells (hMSCs). In this study we systematically investigated the influence of polymeric nanoparticles on the cell functionality and differentiation capacity of hHSCs and hMSCs to obtain a deeper knowledge of the interaction of stem cells and nanoparticles. As model systems of nanoparticles, two sets of either bioinert (polystyrene without carboxylic groups on the surface) or biodegradable (PLLA without magnetite) particles were analyzed. Flow cytometry and microscopy analysis showed high uptake rates and no toxicity for all four tested particles in hMSCs and hHSCs. During the differentiation process, the payload of particles per cell decreased. The PLLA–Fe particle showed a significant increase in the IL-8 release in hMSCs but not in hHSCs. We assume that this is due to an increase of free intracellular iron ions but obviously also depends on the cell type. For hHSCs and hMSCs, lineage differentiation into erythrocytes, granulocytes, and megakaryocytes or adipocytes, osteocytes and chondrocytes, was not influenced by the particles when analyzed with lineage specific cluster of differentiation markers. On the other hand qPCR analysis showed significant changes in the expression of some (but not all) investigated lineage markers for both primary cell types. PMID:25821678

  11. 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).

  12. 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

  13. 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. PMID:26797145

  14. Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage.

    PubMed

    Simpson, Russell M L; Hong, Xuechong; Wong, Mei Mei; Karamariti, Eirini; Bhaloo, Shirin Issa; Warren, Derek; Kong, Wei; Hu, Yanhua; Xu, Qingbo

    2016-05-01

    Deciphering the extracellular signals that regulate SMC differentiation from stem cells is vital to further our understanding of the pathogenesis of vascular disease and for development of cell-based therapies and tissue engineering. Hyaluronan (HA) has emerged as an important component of the stem cell niche, however its role during stem cell differentiation is a complicated and inadequately defined process. This study aimed to investigate the role of HA in embryonic stem cell (ESC) differentiation toward a SMC lineage. ESCs were seeded on collagen-IV in differentiation medium to generate ESC-derived SMCs (esSMCs). Differentiation coincided with increased HA synthase (HAS) 2 expression, accumulation of extracellular HA and its assembly into pericellular matrices. Inhibition of HA synthesis by 4-methylumbelliferone (4MU), removal of the HA coat by hyaluronidase (HYAL) or HAS2 knockdown led to abrogation of SMC gene expression. HA activates ERK1/2 and suppresses EGFR signaling pathways via its principle receptor, CD44. EGFR inactivation coincided with increased binding to CD44, which was further augmented by addition of high molecular weight (HMW)-HA either exogenously or via HAS2 overexpression through adenoviral gene transfer. HMW-HA-stimulated esSMCs displayed a functional role in vascular tissue engineering ex vivo, vasculogenesis in a matrigel plug model and SMC accumulation in neointimal lesions of vein grafts in mice. These findings demonstrate that HAS2-induced HA synthesis and organization drives ESC-SMC differentiation. Thus, remodeling of the HA microenvironment is a critical step in directing stem cell differentiation toward a vascular lineage, highlighting HA as a potential target for treatment of vascular diseases. Stem Cells 2016;34:1225-1238. PMID:26867148

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

    PubMed Central

    Rostovskaya, Maria; Bredenkamp, Nicholas; Smith, Austin

    2015-01-01

    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. PMID:26416676

  16. The origin and early radiation of dinosaurs

    NASA Astrophysics Data System (ADS)

    Brusatte, Stephen L.; Nesbitt, Sterling J.; Irmis, Randall B.; Butler, Richard J.; Benton, Michael J.; Norell, Mark A.

    2010-07-01

    Dinosaurs were remarkably successful during the Mesozoic and one subgroup, birds, remain an important component of modern ecosystems. Although the extinction of non-avian dinosaurs at the end of the Cretaceous has been the subject of intense debate, comparatively little attention has been given to the origin and early evolution of dinosaurs during the Late Triassic and Early Jurassic, one of the most important evolutionary radiations in earth history. Our understanding of this keystone event has dramatically changed over the past 25 years, thanks to an influx of new fossil discoveries, reinterpretations of long-ignored specimens, and quantitative macroevolutionary analyses that synthesize anatomical and geological data. Here we provide an overview of the first 50 million years of dinosaur history, with a focus on the large-scale patterns that characterize the ascent of dinosaurs from a small, almost marginal group of reptiles in the Late Triassic to the preeminent terrestrial vertebrates of the Jurassic and Cretaceous. We provide both a biological and geological background for early dinosaur history. Dinosaurs are deeply nested among the archosaurian reptiles, diagnosed by only a small number of characters, and are subdivided into a number of major lineages. The first unequivocal dinosaurs are known from the late Carnian of South America, but the presence of their sister group in the Middle Triassic implies that dinosaurs possibly originated much earlier. The three major dinosaur lineages, theropods, sauropodomorphs, and ornithischians, are all known from the Triassic, when continents were joined into the supercontinent Pangaea and global climates were hot and arid. Although many researchers have long suggested that dinosaurs outcompeted other reptile groups during the Triassic, we argue that the ascent of dinosaurs was more of a matter of contingency and opportunism. Dinosaurs were overshadowed in most Late Triassic ecosystems by crocodile-line archosaurs and showed no signs of outcompeting their rivals. Instead, the rise of dinosaurs was a two-stage process, as dinosaurs expanded in taxonomic diversity, morphological disparity, and absolute faunal abundance only after the extinction of most crocodile-line reptiles and other groups.

  17. 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.

  18. 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. PMID:26515645

  19. Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells.

    PubMed

    Benchetrit, Hana; Herman, Shay; van Wietmarschen, Niek; Wu, Tao; Makedonski, Kirill; Maoz, Noam; Yom Tov, Nataly; Stave, Danielle; Lasry, Rachel; Zayat, Valery; Xiao, Andrew; Lansdorp, Peter M; Sebban, Shulamit; Buganim, Yosef

    2015-11-01

    Induced pluripotent stem cells (iPSCs) undergo extensive nuclear reprogramming and are generally indistinguishable from embryonic stem cells (ESCs) in their functional capacity and transcriptome and DNA methylation profiles. However, direct conversion of cells from one lineage to another often yields incompletely reprogrammed, functionally compromised cells, raising the question of whether pluripotency is required to achieve a high degree of nuclear reprogramming. Here, we show that transient expression of Gata3, Eomes, and Tfap2c in mouse fibroblasts induces stable, transgene-independent trophoblast stem-like cells (iTSCs). iTSCs possess transcriptional profiles highly similar to blastocyst-derived TSCs, with comparable methylation and H3K27ac patterns and genome-wide H2A.X deposition. iTSCs generate trophoectodermal lineages upon differentiation, form hemorrhagic lesions, and contribute to developing placentas in chimera assays, indicating a high degree of nuclear reprogramming, with no evidence of passage through a transient pluripotent state. Together, these data demonstrate that extensive nuclear reprogramming can be achieved independently of pluripotency. PMID:26412562

  20. Lymphoid lineage differentiation potential of mouse nuclear transfer embryonic stem cells.

    PubMed

    Eslami-Arshaghi, Tarlan; Salehi, Mohammad; Soleimani, Masoud; Gholipourmalekabadi, Mazaher; Mossahebi-Mohammadi, Majid; Ardeshirylajimi, Abdolreza; Rajabi, Hoda

    2015-09-01

    Stem cells therapy is considered as an efficient strategy for the treatment of some diseases. Nevertheless, some obstacles such as probability of rejection by the immune system limit applications of this strategy. Therefore, several efforts have been made to overcome this among which using the induced pluripotent stem cells (iPSCs) and nuclear transfer embryonic stem cell (nt-ESCs) are the most efficient strategies. The objective of this study was to evaluate the differentiation potential of the nt-ESCs to lymphoid lineage in the presence of IL-7, IL-3, FLT3-ligand and TPO growth factors invitro. To this end, the nt-ESCs cells were prepared and treated with aforementioned growth factors for 7 and 14 days. Then, the cells were examined for expression of lymphoid markers (CD3, CD25, CD127 and CD19) by quantitative PCR (q-PCR) and flow cytometry. An increased expression of CD19 and CD25 markers was observed in the treated cells compared with the negative control samples by day 7. After 14 days, the expression level of all the tested CD markers significantly increased in the treated groups in comparison with the control. The current study reveals the potential of the nt-ESCs in differentiation to lymphoid lineage in the presence of defined growth factors. PMID:26239678

  1. Directing Human Induced Pluripotent Stem Cells into a Neurosensory Lineage for Auditory Neuron Replacement

    PubMed Central

    Gunewardene, Niliksha; Bergen, Nicole Van; Crombie, Duncan; Needham, Karina; Dottori, Mirella

    2014-01-01

    Abstract Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ßIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages. PMID:25126480

  2. Directing human induced pluripotent stem cells into a neurosensory lineage for auditory neuron replacement.

    PubMed

    Gunewardene, Niliksha; Bergen, Nicole Van; Crombie, Duncan; Needham, Karina; Dottori, Mirella; Nayagam, Bryony A

    2014-08-01

    Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ßIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages. PMID:25126480

  3. New stem-sauropodomorph (Dinosauria, Saurischia) from the Triassic of Brazil

    NASA Astrophysics Data System (ADS)

    Cabreira, Sergio F.; Schultz, Cesar L.; Bittencourt, Jonathas S.; Soares, Marina B.; Fortier, Daniel C.; Silva, Lúcio R.; Langer, Max C.

    2011-12-01

    Post-Triassic theropod, sauropodomorph, and ornithischian dinosaurs are readily recognized based on the set of traits that typically characterize each of these groups. On the contrary, most of the early members of those lineages lack such specializations, but share a range of generalized traits also seen in more basal dinosauromorphs. Here, we report on a new Late Triassic dinosaur from the Santa Maria Formation of Rio Grande do Sul, southern Brazil. The specimen comprises the disarticulated partial skeleton of a single individual, including most of the skull bones. Based on four phylogenetic analyses, the new dinosaur fits consistently on the sauropodomorph stem, but lacks several typical features of sauropodomorphs, showing dinosaur plesiomorphies together with some neotheropod traits. This is not an exception among basal dinosaurs, the early radiation of which is characterized by a mosaic pattern of character acquisition, resulting in the uncertain phylogenetic placement of various early members of the group.

  4. Dinosaurs and the Cretaceous Terrestrial Revolution

    PubMed Central

    Lloyd, Graeme T; Davis, Katie E; Pisani, Davide; Tarver, James E; Ruta, Marcello; Sakamoto, Manabu; Hone, David W.E; Jennings, Rachel; Benton, Michael J

    2008-01-01

    The observed diversity of dinosaurs reached its highest peak during the mid- and Late Cretaceous, the 50 Myr that preceded their extinction, and yet this explosion of dinosaur diversity may be explained largely by sampling bias. It has long been debated whether dinosaurs were part of the Cretaceous Terrestrial Revolution (KTR), from 125–80 Myr ago, when flowering plants, herbivorous and social insects, squamates, birds and mammals all underwent a rapid expansion. Although an apparent explosion of dinosaur diversity occurred in the mid-Cretaceous, coinciding with the emergence of new groups (e.g. neoceratopsians, ankylosaurid ankylosaurs, hadrosaurids and pachycephalosaurs), results from the first quantitative study of diversification applied to a new supertree of dinosaurs show that this apparent burst in dinosaurian diversity in the last 18 Myr of the Cretaceous is a sampling artefact. Indeed, major diversification shifts occurred largely in the first one-third of the group's history. Despite the appearance of new clades of medium to large herbivores and carnivores later in dinosaur history, these new originations do not correspond to significant diversification shifts. Instead, the overall geometry of the Cretaceous part of the dinosaur tree does not depart from the null hypothesis of an equal rates model of lineage branching. Furthermore, we conclude that dinosaurs did not experience a progressive decline at the end of the Cretaceous, nor was their evolution driven directly by the KTR. PMID:18647715

  5. Dinosaurs and the Cretaceous Terrestrial Revolution.

    PubMed

    Lloyd, Graeme T; Davis, Katie E; Pisani, Davide; Tarver, James E; Ruta, Marcello; Sakamoto, Manabu; Hone, David W E; Jennings, Rachel; Benton, Michael J

    2008-11-01

    The observed diversity of dinosaurs reached its highest peak during the mid- and Late Cretaceous, the 50 Myr that preceded their extinction, and yet this explosion of dinosaur diversity may be explained largely by sampling bias. It has long been debated whether dinosaurs were part of the Cretaceous Terrestrial Revolution (KTR), from 125-80 Myr ago, when flowering plants, herbivorous and social insects, squamates, birds and mammals all underwent a rapid expansion. Although an apparent explosion of dinosaur diversity occurred in the mid-Cretaceous, coinciding with the emergence of new groups (e.g. neoceratopsians, ankylosaurid ankylosaurs, hadrosaurids and pachycephalosaurs), results from the first quantitative study of diversification applied to a new supertree of dinosaurs show that this apparent burst in dinosaurian diversity in the last 18 Myr of the Cretaceous is a sampling artefact. Indeed, major diversification shifts occurred largely in the first one-third of the group's history. Despite the appearance of new clades of medium to large herbivores and carnivores later in dinosaur history, these new originations do not correspond to significant diversification shifts. Instead, the overall geometry of the Cretaceous part of the dinosaur tree does not depart from the null hypothesis of an equal rates model of lineage branching. Furthermore, we conclude that dinosaurs did not experience a progressive decline at the end of the Cretaceous, nor was their evolution driven directly by the KTR. PMID:18647715

  6. Lineage-Specific Purification of Neural Stem/Progenitor Cells From Differentiated Mouse Induced Pluripotent Stem Cells

    PubMed Central

    Maruyama, Masato; Yamashita, Yuji; Kase, Masahiko; Trifonov, Stefan

    2013-01-01

    Since induced pluripotent stem (iPS) cells have differentiation potential into all three germ layer-derived tissues, efficient purification of target cells is required in many fields of iPS research. One useful strategy is isolation of desired cells from differentiated iPS cells by lineage-specific expression of a drug-resistance gene, followed by drug selection. With this strategy, we purified neural stem/progenitor cells (NSCs), a good candidate source for regenerative therapy, from differentiated mouse iPS cells. We constructed a bicistronic expression vector simultaneously expressing blasticidin S resistance gene and DsRed under the control of tandem enhancer of a 257-base pair region of nestin second intron, an NSC-specific enhancer. This construct was efficiently inserted into the iPS genome by piggyBac transposon-mediated gene transfer, and the established subclone was differentiated into NSCs in the presence or absence of blasticidin S. Consequently, incubation with blasticidin S led to purification of NSCs from differentiated iPS cells. Our results suggest that a lineage-specific drug selection strategy is useful for purification of NSCs from differentiated iPS cells and that this strategy can be applied for the purification of other cell types. PMID:23694811

  7. Dinosaur Dioramas.

    ERIC Educational Resources Information Center

    Scheinkman, Nancy

    2001-01-01

    Describes an art project for second-grade students where in over five class periods, they create fired clay dinosaur sculptures with dioramas as the background. States that this project, the culminating activity for a sculpture unit, teaches students many art terms and uses of different media. (CMK)

  8. Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations.

    PubMed

    Loh, Kyle M; Ang, Lay Teng; Zhang, Jingyao; Kumar, Vibhor; Ang, Jasmin; Auyeong, Jun Qiang; Lee, Kian Leong; Choo, Siew Hua; Lim, Christina Y Y; Nichane, Massimo; Tan, Junru; Noghabi, Monireh Soroush; Azzola, Lisa; Ng, Elizabeth S; Durruthy-Durruthy, Jens; Sebastiano, Vittorio; Poellinger, Lorenz; Elefanty, Andrew G; Stanley, Edouard G; Chen, Qingfeng; Prabhakar, Shyam; Weissman, Irving L; Lim, Bing

    2014-02-01

    Human pluripotent stem cell (hPSC) differentiation typically yields heterogeneous populations. Knowledge of signals controlling embryonic lineage bifurcations could efficiently yield desired cell types through exclusion of alternate fates. Therefore, we revisited signals driving induction and anterior-posterior patterning of definitive endoderm to generate a coherent roadmap for endoderm differentiation. With striking temporal dynamics, BMP and Wnt initially specified anterior primitive streak (progenitor to endoderm), yet, 24 hr later, suppressed endoderm and induced mesoderm. At lineage bifurcations, cross-repressive signals separated mutually exclusive fates; TGF-β and BMP/MAPK respectively induced pancreas versus liver from endoderm by suppressing the alternate lineage. We systematically blockaded alternate fates throughout multiple consecutive bifurcations, thereby efficiently differentiating multiple hPSC lines exclusively into endoderm and its derivatives. Comprehensive transcriptional and chromatin mapping of highly pure endodermal populations revealed that endodermal enhancers existed in a surprising diversity of "pre-enhancer" states before activation, reflecting the establishment of a permissive chromatin landscape as a prelude to differentiation. PMID:24412311

  9. Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages.

    PubMed

    Abagnale, Giulio; Steger, Michael; Nguyen, Vu Hoa; Hersch, Nils; Sechi, Antonio; Joussen, Sylvia; Denecke, Bernd; Merkel, Rudolf; Hoffmann, Bernd; Dreser, Alice; Schnakenberg, Uwe; Gillner, Arnold; Wagner, Wolfgang

    2015-08-01

    Surface topography impacts on cell growth and differentiation, but it is not trivial to generate defined surface structures and to assess the relevance of specific topographic parameters. In this study, we have systematically compared in vitro differentiation of mesenchymal stem cells (MSCs) on a variety of groove/ridge structures. Micro- and nano-patterns were generated in polyimide using reactive ion etching or multi beam laser interference, respectively. These structures affected cell spreading and orientation of human MSCs, which was also reflected in focal adhesions morphology and size. Time-lapse demonstrated directed migration parallel to the nano-patterns. Overall, surface patterns clearly enhanced differentiation of MSCs towards specific lineages: 15 μm ridges increased adipogenic differentiation whereas 2 μm ridges enhanced osteogenic differentiation. Notably, nano-patterns with a periodicity of 650 nm increased differentiation towards both osteogenic and adipogenic lineages. However, in absence of differentiation media surface structures did neither induce differentiation, nor lineage-specific gene expression changes. Furthermore, nanostructures did not affect the YAP/TAZ complex, which is activated by substrate stiffness. Our results provide further insight into how structuring of tailored biomaterials and implant interfaces - e.g. by multi beam laser interference in sub-micrometer scale - do not induce differentiation of MSCs per se, but support their directed differentiation. PMID:26026844

  10. Equine-Induced Pluripotent Stem Cells Retain Lineage Commitment Toward Myogenic and Chondrogenic Fates.

    PubMed

    Quattrocelli, Mattia; Giacomazzi, Giorgia; Broeckx, Sarah Y; Ceelen, Liesbeth; Bolca, Selin; Spaas, Jan H; Sampaolesi, Maurilio

    2016-01-12

    Induced pluripotent stem cells (iPSCs) hold great potential not only for human but also for veterinary purposes. The equine industry must often deal with health issues concerning muscle and cartilage, where comprehensive regenerative strategies are still missing. In this regard, a still open question is whether equine iPSCs differentiate toward muscle and cartilage, and whether donor cell type influences their differentiation potential. We addressed these questions through an isogenic system of equine iPSCs obtained from myogenic mesoangioblasts (MAB-iPSCs) and chondrogenic mesenchymal stem cells (MSC-iPSCs). Despite similar levels of pluripotency characteristics, the myogenic differentiation appeared enhanced in MAB-iPSCs. Conversely, the chondrogenic differentiation was augmented in MSC-iPSCs through both teratoma and in vitro differentiation assays. Thus, our data suggest that equine iPSCs can differentiate toward the myogenic and chondrogenic lineages, and can present a skewed differentiation potential in favor of the source cell lineage. PMID:26771353

  11. Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.

    PubMed

    Horvay, Katja; Jard, Thierry; Casagranda, Franca; Perreau, Victoria M; Haigh, Katharina; Nefzger, Christian M; Akhtar, Reyhan; Gridley, Thomas; Berx, Geert; Haigh, Jody J; Barker, Nick; Polo, Jose M; Hime, Gary R; Abud, Helen E

    2015-05-12

    Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage. PMID:25759216

  12. Equine-Induced Pluripotent Stem Cells Retain Lineage Commitment Toward Myogenic and Chondrogenic Fates

    PubMed Central

    Quattrocelli, Mattia; Giacomazzi, Giorgia; Broeckx, Sarah Y.; Ceelen, Liesbeth; Bolca, Selin; Spaas, Jan H.; Sampaolesi, Maurilio

    2016-01-01

    Summary Induced pluripotent stem cells (iPSCs) hold great potential not only for human but also for veterinary purposes. The equine industry must often deal with health issues concerning muscle and cartilage, where comprehensive regenerative strategies are still missing. In this regard, a still open question is whether equine iPSCs differentiate toward muscle and cartilage, and whether donor cell type influences their differentiation potential. We addressed these questions through an isogenic system of equine iPSCs obtained from myogenic mesoangioblasts (MAB-iPSCs) and chondrogenic mesenchymal stem cells (MSC-iPSCs). Despite similar levels of pluripotency characteristics, the myogenic differentiation appeared enhanced in MAB-iPSCs. Conversely, the chondrogenic differentiation was augmented in MSC-iPSCs through both teratoma and in vitro differentiation assays. Thus, our data suggest that equine iPSCs can differentiate toward the myogenic and chondrogenic lineages, and can present a skewed differentiation potential in favor of the source cell lineage. PMID:26771353

  13. Sprouty1 is a critical regulatory switch of mesenchymal stem cell lineage allocation

    PubMed Central

    Urs, Sumithra; Venkatesh, Deepak; Tang, Yuefeng; Henderson, Terry; Yang, Xuehui; Friesel, Robert E.; Rosen, Clifford J.; Liaw, Lucy

    2010-01-01

    Development of bone and adipose tissue are linked processes arising from a common progenitor cell, but having an inverse relationship in disease conditions such as osteoporosis. Cellular differentiation of both tissues relies on growth factor cues, and we focus this study on Sprouty1 (Spry1), an inhibitor of growth factor signaling. We tested whether Spry1 can modify the development of fat cells through its activity in regulating growth factors known to be important for adipogenesis. We utilized conditional expression and genetic-null mouse models of Spry1 in adipocytes using the fatty acid binding promoter (aP2). Conditional deletion of Spry1 results in 10% increased body fat and decreased bone mass. This phenotype was rescued on Spry1 expression, which results in decreased body fat and increased bone mass. Ex vivo bone marrow experiments indicate Spry1 in bone marrow and adipose progenitor cells favors differentiation of osteoblasts at the expense of adipocytes by suppressing CEBP-β and PPARγ while up regulating TAZ. Age and gender-matched littermates expressing only Cre recombinase were used as controls. Spry1 is a critical regulator of adipocyte differentiation and mesenchymal stem cell (MSC) lineage allocation, potentially acting through regulation of CEBP-β and TAZ.—Urs, S., Venkatesh, D., Tang, Y., Henderson, T., Yang, X., Friesel, R. E., Rosen, C. J., Liaw, L. Sprouty1 is a critical regulatory switch of mesenchymal stem cell lineage allocation. PMID:20410440

  14. 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

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

    PubMed

    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. PMID:26114597

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

    SciTech Connect

    Nishikawa, Masaki; University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 ; Yanagawa, Naomi; University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 ; Kojima, Nobuhiko; Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto; University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343

    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 lineages 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 cells was effective in inducing MM and UB markers, respectively. We also observed the emergence and gradual increase of cell populations expressing progenitor cell marker CD24 from Stage I to Stage III. These CD24{sup +} cells correlated with higher levels of expression of Brachyury at stage I, Pax2 and Lim1 at stage II and MM markers, such as WT1 and Cadherin 11, after exposure to UB-conditioned media at stage III. In conclusion, our results show that stepwise induction by tracing in vivo developmental stages was effective to generate renal lineage progenitor cells from mESC, and CD24 may serve as a useful surface marker for renal lineage cells at stage II and MM cells at stage III.

  17. High glucose suppresses embryonic stem cell differentiation into neural lineage cells.

    PubMed

    Yang, Penghua; Shen, Wei-Bin; Albert Reece, E; Chen, Xi; Yang, Peixin

    2016-04-01

    Abnormal neurogenesis occurs during embryonic development in human diabetic pregnancies and in animal models of diabetic embryopathy. Our previous studies in a mouse model of diabetic embryopathy have implicated that high glucose of maternal diabetes delays neurogenesis in the developing neuroepithelium leading to neural tube defects. However, the underlying process in high glucose-impaired neurogenesis is uncharacterized. Neurogenesis from embryonic stem (ES) cells provides a valuable model for understanding the abnormal neural lineage development under high glucose conditions. ES cells are commonly generated and maintained in high glucose (approximately 25 mM glucose). Here, the mouse ES cell line, E14, was gradually adapted to and maintained in low glucose (5 mM), and became a glucose responsive E14 (GR-E14) line. High glucose induced the endoplasmic reticulum stress marker, CHOP, in GR-E14 cells. Under low glucose conditions, the GR-E14 cells retained their pluripotency and capability to differentiate into neural lineage cells. GR-E14 cell differentiation into neural stem cells (Sox1 and nestin positive cells) was inhibited by high glucose. Neuron (Tuj1 positive cells) and glia (GFAP positive cells) differentiation from GR-E14 cells was also suppressed by high glucose. In addition, high glucose delayed GR-E14 differentiation into neural crest cells by decreasing neural crest markers, paired box 3 (Pax3) and paired box 7 (Pax7). Thus, high glucose impairs ES cell differentiation into neural lineage cells. The low glucose adapted and high glucose responsive GR-E14 cell line is a useful in vitro model for assessing the adverse effect of high glucose on the development of the central nervous system. PMID:26940741

  18. Impact of Tissue-Specific Stem Cells on Lineage-Specific Differentiation: A Focus on the Musculoskeletal System

    PubMed Central

    Pizzute, Tyler; Lynch, Kevin; Pei, Ming

    2014-01-01

    Tissue-specific stem cells are found throughout the body and, with proper intervention and environmental cues, these stem cells exercise their capabilities for differentiation into several lineages to form cartilage, bone, muscle, and adipose tissue in vitro and in vivo. Interestingly, it has been widely demonstrated that they do not differentiate with the same efficacy during lineage-specific differentiation studies, as the tissue-specific stem cells are generally more effective when differentiating toward the tissues from which they were derived. This review focuses on four mesodermal lineages for tissue-specific stem cell differentiation: adipogenesis, chondrogenesis, myogenesis, and osteogenesis. It is intended to give insight into current multilineage differentiation and comparative research, highlight and contrast known trends regarding differentiation, and introduce supporting evidence which demonstrates particular tissue-specific stem cells’ superiority in lineage-specific differentiation, along with their resident tissue origins and natural roles. In addition, some epigenetic and transcriptomic differences between stem cells which may explain the observed trends are discussed. PMID:25113801

  19. Small SSEA-4-positive cells from human ovarian cell cultures: related to embryonic stem cells and germinal lineage?

    PubMed Central

    2013-01-01

    Background It has already been found that very small embyronic-like stem cells (VSELs) are present in adult human tissues and organs. The aim of this study was to find if there exists any similar population of cells in cell cultures of reproductive tissues and embryonic stem cells, and if these cells have any relation to pluripotency and germinal lineage. Methods and results Here we report that a population of small SSEA-4-positive cells with diameters of up to 4 μm was isolated by fluorescence-activated cell sorting (FACS) from the human ovarian cell cultures after enzymatic degradation of adult cortex tissues. These small cells – putative ovarian stem cells – were also observed during cell culturing of up to 6 months and more. In general, small putative ovarian stem cells, isolated by FACS, showed a relatively low gene expression profile when compared to human embryonic stem cells (hESCs) and human adult fibroblasts; this may reflect the quiescent state of these cells. In spite of that, small putative ovarian stem cells expressed several genes related to primordial germ cells (PGCs), pluripotency and germinal lineage, including VASA. The PGC-related gene PRDM1 was strongly expressed in small putative ovarian stem cells; in both hESCs and fibroblasts it was significantly down-regulated. In addition, putative ovarian stem cells expressed other PGC-related genes, such as PRDM14 and DPPA3. Most of the pluripotency and germinal lineage-related genes were up-regulated in hESCs (except VASA). When compared to fibroblasts, there were several pluripotency-related genes, which were up-regulated in small putative ovarian stem cells. Similar populations of small cells were also isolated by FACS from human testicular and hESC cultures. Conclusions Our results confirm the potential embryonic-like character of small putative stem cells isolated from human adult ovaries and their possible relation to germinal lineage. PMID:23570331

  20. Dinosaur evolution. A Jurassic ornithischian dinosaur from Siberia with both feathers and scales.

    PubMed

    Godefroit, Pascal; Sinitsa, Sofia M; Dhouailly, Danielle; Bolotsky, Yuri L; Sizov, Alexander V; McNamara, Maria E; Benton, Michael J; Spagna, Paul

    2014-07-25

    Middle Jurassic to Early Cretaceous deposits from northeastern China have yielded varied theropod dinosaurs bearing feathers. Filamentous integumentary structures have also been described in ornithischian dinosaurs, but whether these filaments can be regarded as part of the evolutionary lineage toward feathers remains controversial. Here we describe a new basal neornithischian dinosaur from the Jurassic of Siberia with small scales around the distal hindlimb, larger imbricated scales around the tail, monofilaments around the head and the thorax, and more complex featherlike structures around the humerus, the femur, and the tibia. The discovery of these branched integumentary structures outside theropods suggests that featherlike structures coexisted with scales and were potentially widespread among the entire dinosaur clade; feathers may thus have been present in the earliest dinosaurs. PMID:25061209

  1. Axes of differentiation in breast cancer: untangling stemness, lineage identity, and the epithelial to mesenchymal transition.

    PubMed

    Granit, Roy Z; Slyper, Michal; Ben-Porath, Ittai

    2014-01-01

    Differentiation-associated regulatory programs are central in determining tumor phenotype, and contribute to heterogeneity between tumors and between individual cells within them. The transcriptional programs that control luminal and basal lineage identity in the normal mammary epithelium, as well as progenitor and stem cell function, are active in breast cancers, and show distinct associations with different disease subtypes. Also active in some tumors is the epithelial to mesenchymal transition (EMT) program, which endows carcinoma cells with mesenchymal as well as stem cell traits. The differentiation state of breast cancer cells is thus dictated by the complex combination of regulatory programs, and these can dramatically affect tumor growth and metastatic capacity. Breast cancer differentiation is often viewed along an axis between a basal–mesenchymal–stem cell state and a luminal–epithelial–differentiated state. Here we consider the links, as well as the distinctions, between the three components of this axis: basal versus luminal, mesenchymal versus epithelial, and stem cell versus differentiated identity. Analysis on a multidimensional scale, in which each of these axes is assessed separately, may offer increased resolution of tumor differentiation state. Cancer cells possessing a high degree of stemness would display increased capacity to shift between positions on such a multidimensional scale, and to acquire intermediate phenotypes on its different axes. Further molecular analysis of breast cancer cells with a focus on single-cell profiling, and the development of improved tools for dissection of the circuits controlling gene activity, are essential for the elucidation of the programs dictating breast cancer differentiation state. PMID:24741710

  2. Feathered Dinosaurs

    NASA Astrophysics Data System (ADS)

    Norell, Mark A.; Xu, Xing

    2005-01-01

    Recent fossil discoveries from Early Cretaceous rocks of Liaoning Province, China, have provided a wealth of spectacular specimens. Included in these are the remains of several different kinds of small theropod dinosaurs, many of which are extremely closely related to modern birds. Unique preservation conditions allowed soft tissues of some of these specimens to be preserved. Many dinosaur specimens that preserve feathers and other types of integumentary coverings have been recovered. These fossils show a progression of integumentary types from simple fibers to feathers of modern aspect. The distribution of these features on the bodies of these animals is surprising in that some show large tail plumes, whereas others show the presence of wing-like structures on both fore and hind limbs. The phylogenetic distribution of feather types is highly congruent with models of feather evolution developed from developmental biology.

  3. 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

  4. Adipose derived mesenchymal stem cells express keratinocyte lineage markers in a co-culture model.

    PubMed

    Irfan-Maqsood, M; Matin, M M; Heirani-Tabasi, A; Bahrami, M; Naderi-Meshkin, H; Mirahmadi, M; Hassanzadeh, H; Sanjar Moussavi, N; Raza-Shah, H; Raeesolmohaddeseen, M; Bidkhori, H; Bahrami, A R

    2016-01-01

    Cutaneous wound healing is a complex type of biological event involving proliferation, differentiation, reprograming, trans/de-differentiation, recruitment, migration, and apoptosis of a number of cells (keratinocytes, fibroblasts, endothelial cells, nerve cells and stem cells) to regenerate a multi-layered tissue that is damaged by either internal or external factors. The exact regeneration mechanism of damaged skin is still unknown but the epithelial and other kinds of stem cells located in skin play crucial roles in the healing process. In this work, a co-culture model composed of adipose derived mesenchymal stem cells and keratinocytes was developed to understand the cellular differentiation behaviour in wound healing. Human mesenchymal stem cells were isolated from waste lipoaspirates. Keratinocytes were isolated from neonatal rats skin as well from human adult skin. Both types of cells were cultured and their culturing behaviour was observed microscopically under regular intervals of time. The identity of both cells was confirmed by flow cytometry and qRT-PCR. Cells were co-cultured under the proposed co-culturing model and the model was observed for 7, 14 and 21 days. The cellular behaviour was studied based on change in morphology, colonization, stratification, migration and expression of molecular markers. Expression of molecular markers was studied at transcriptional level and change in cellular morphology and migration capabilities was observed under the invert microscope regularly. Successfully isolated and characterized mesenchymal stem cells were found to express keratinocyte lineage markers i.e. K5, K10, K14, K18, K19 and Involucrin when co-cultured with keratinocytes after 14 and 21 days. Their expression was found to increase by increasing the time span of cell culturing. The keratinocyte colonies started to disappear after 10 days of culturing which might be due to stratification process initiated by possibly transdifferentiated stem cells. It can be concluded that mesenchymal stem cells can regenerate the damaged skin if transplanted to damaged area but for their successful differentiation and enhanced regeneration, they need a population of keratinocytes in situ which need further experiments for validation of co-culture model and its potential for being used in clinics. PMID:27188869

  5. Dynamic loading of electrospun yarns guides mesenchymal stem cells towards a tendon lineage

    PubMed Central

    Bosworth, L.A.; Rathbone, S.R.; Bradley, R.S.; Cartmell, S.H.

    2014-01-01

    Alternative strategies are required when autograft tissue is not sufficient or available to reconstruct damaged tendons. Electrospun fibre yarns could provide such an alternative. This study investigates the seeding of human mesenchymal stem cells (hMSC) on electrospun yarns and their response when subjected to dynamic tensile loading. Cell seeded yarns sustained 3600 cycles per day for 21 days. Loaded yarns demonstrated a thickened cell layer around the scaffold׳s exterior compared to statically cultured yarns, which would suggest an increased rate of cell proliferation and/or matrix deposition, whilst maintaining a predominant uniaxial cell orientation. Tensile properties of cell-seeded yarns increased with time compared to acellular yarns. Loaded scaffolds demonstrated an up-regulation in several key tendon genes, including collagen Type I. This study demonstrates the support of hMSCs on electrospun yarns and their differentiation towards a tendon lineage when mechanically stimulated. PMID:25129861

  6. Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage

    PubMed Central

    Mak, Sally K.; Huang, Y. Anne; Iranmanesh, Shifteh; Vangipuram, Malini; Sundararajan, Ramya; Nguyen, Loan; Langston, J. William; Schüle, Birgitt

    2012-01-01

    Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson's disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage. PMID:22567022

  7. Essential role of PU.1 in maintenance of mixed lineage leukemia-associated leukemic stem cells

    PubMed Central

    Aikawa, Yukiko; Yamagata, Kazutsune; Katsumoto, Takuo; Shima, Yutaka; Shino, Mika; Stanley, E Richard; Cleary, Michael L; Akashi, Koichi; Tenen, Daniel G; Kitabayashi, Issay

    2015-01-01

    Acute myeloid leukemia is a clonal malignant disorder derived from a small number of leukemic stem cells (LSCs). Rearrangements of the mixed lineage leukemia (MLL) gene are found in acute myeloid leukemia associated with poor prognosis. The upregulation of Hox genes is critical for LSC induction and maintenance, but is unlikely to support malignancy and the high LSC frequency observed in MLL leukemias. The present study shows that MLL fusion proteins interact with the transcription factor PU.1 to activate the transcription of CSF-1R, which is critical for LSC activity. Acute myeloid leukemia is cured by either deletion of PU.1 or ablation of cells expressing CSF-1R. Kinase inhibitors specific for CSF-1R prolong survival time. These findings indicate that PU.1-mediated upregulation of CSF-1R is a critical effector of MLL leukemogenesis. PMID:25529853

  8. 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. PMID:16137230

  9. Directed differentiation of human pluripotent stem cells along the pancreatic endocrine lineage.

    PubMed

    Van Hoof, Dennis; Liku, Muluye E

    2013-01-01

    Many research groups are engaged in using human pluripotent stem cells (hPSCs) to generate surrogate pancreatic β-cells for transplantation into diabetic patients. However, to our knowledge, there is no report on the successful generation of glucose-responsive insulin-producing β-cells from hPSCs in vitro. Below, we outline a method that is based on published protocols as well as our own experience by which one can differentiate hPSCs along the pancreatic lineage to generate insulin-producing β-cell-like cells. The protocol, which spans five distinct stages, is an attempt to recapitulate the derivation of pancreatic β-cells in vitro as they form in the developing embryo. We included details on materials and techniques, suggest ways to customize it to your hPSC line of choice, added notes on how to monitor and analyze the cells during differentiation, and indicate what results can be expected. PMID:23546752

  10. Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells

    PubMed Central

    Rouhani, Foad J.; Nik-Zainal, Serena; Wuster, Arthur; Li, Yilong; Conte, Nathalie; Koike-Yusa, Hiroko; Kumasaka, Natsuhiko; Vallier, Ludovic; Yusa, Kosuke; Bradley, Allan

    2016-01-01

    The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50–70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer. PMID:27054363

  11. Lineage selection of functional and cryopreservable human embryonic stem cell-derived neurons.

    PubMed

    Ladewig, Julia; Koch, Philipp; Endl, Elmar; Meiners, Banu; Opitz, Thoralf; Couillard-Despres, Sebastien; Aigner, Ludwig; Brüstle, Oliver

    2008-07-01

    A major prerequisite for the biomedical application of human embryonic stem cells (hESC) is the derivation of defined and homogeneous somatic cell types. Here we present a human doublecortin (DCX) promoter-based lineage-selection strategy for the generation of purified hESC-derived immature neurons. After transfection of hESC-derived neural precursors with a DCX-enhanced green fluorescent protein construct, fluorescence-activated cell sorting enables the enrichment of immature human neurons at purities of up to 95%. Selected neurons undergo functional maturation and are able to establish synaptic connections. Considering that the applicability of purified hESC-derived neurons would largely benefit from an efficient cryopreservation technique, we set out to devise defined freezing conditions involving caspase inhibition, which yield post-thaw recovery rates of up to 83%. Combined with our lineage-selection procedure this cryopreservation technique enables the generation of human neurons in a ready-to-use format for a large variety of biomedical applications. PMID:18420830

  12. Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.

    PubMed

    Rouhani, Foad J; Nik-Zainal, Serena; Wuster, Arthur; Li, Yilong; Conte, Nathalie; Koike-Yusa, Hiroko; Kumasaka, Natsuhiko; Vallier, Ludovic; Yusa, Kosuke; Bradley, Allan

    2016-04-01

    The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer. PMID:27054363

  13. Accelerated Neuronal Differentiation Toward Motor Neuron Lineage from Human Embryonic Stem Cell Line (H9)

    PubMed Central

    Lu, David; Chen, Eric Y.T.; Lee, Philip; Wang, Yung-Chen; Ching, Wendy; Markey, Christopher; Gulstrom, Chase; Chen, Li-Ching; Nguyen, Thien

    2015-01-01

    Motor neurons loss plays a pivotal role in the pathoetiology of various debilitating diseases such as, but not limited to, amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, pseudobulbar palsy, and spinal muscular atrophy. However, advancement in motor neuron replacement therapy has been significantly constrained by the difficulties in large-scale production at a cost-effective manner. Current methods to derive motor neuron heavily rely on biochemical stimulation, chemical biological screening, and complex physical cues. These existing methods are seriously challenged by extensive time requirements and poor yields. An innovative approach that overcomes prior hurdles and enhances the rate of successful motor neuron transplantation in patients is of critical demand. Iron, a trace element, is indispensable for the normal development and function of the central nervous system. Whether ferric ions promote neuronal differentiation and subsequently promote motor neuron lineage has never been considered. Here, we demonstrate that elevated iron concentration can drastically accelerate the differentiation of human embryonic stem cells (hESCs) toward motor neuron lineage potentially via a transferrin mediated pathway. HB9 expression in 500 nM iron-treated hESCs is approximately twofold higher than the control. Moreover, iron treatment generated more matured and functional motor neuron-like cells that are ∼1.5 times more sensitive to depolarization when compared to the control. Our methodology renders an expedited approach to harvest motor neuron-like cells for disease, traumatic injury regeneration, and drug screening. PMID:25036750

  14. 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

    2016-01-01

    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. PMID:26986509

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

    PubMed Central

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

    2016-01-01

    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. PMID:26986509

  16. 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. PMID:23660249

  17. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in Hematopoietic Stem Cells

    PubMed Central

    Ng, Samuel Yao-Ming; Yoshida, Toshimi; Zhang, Jiangwen; Georgopoulos, Katia

    2010-01-01

    Summary Here we investigate the mechanisms that underlie the induction of developmental potential and establishment of cell fate during early hematopoiesis. A cascade of lineage-affiliated gene expression signatures, primed in hematopoietic stem cells (HSC) and differentially propagated in lineage-restricted progenitors, is identified. First evidence is provided for a stochastic sampling of lymphoid, erythroid and myeloid transcripts in HSC and multipotent progenitors (MPP). Multi-lineage priming is subsequently resolved upon lineage restrictions. Nonetheless, an unexpected association of lymphoid and myeloid signatures is detected past a nominal myeloid restriction point and a previously unappreciated lymphoid potential is revealed for this stage in development. New insight is provided into Ikaros' role as a bivalent regulator of multi-lineage priming during early hematopoiesis. Whereas Ikaros is responsible for activation of a cascade of lymphoid signatures in the HSC, at subsequent restriction points it is also involved in the repression of lineage-inappropriate signatures including stem cell-specific genes. PMID:19345118

  18. Lymphoid enhancer factor 1-mediated Wnt signaling promotes the initiation of trophoblast lineage differentiation in mouse embryonic stem cells.

    PubMed

    He, Shuyang; Pant, Disha; Schiffmacher, Andrew; Meece, Ashley; Keefer, Carol L

    2008-04-01

    Embryonic stem (ES) cells can differentiate into all three embryonic germ layers but rarely into trophectoderm (TE) lineages that contribute to the placenta, although TE differentiation can be initiated by genetic manipulation of key genes involved in TE development. We demonstrate that Wnt signaling can initiate TE lineage differentiation by triggering an appropriate cue, caudal-related homeobox 2 (Cdx2). Overexpression and RNA interference knockdown studies indicate that Cdx2 induction in response to Wnt3a is mediated by lymphoid enhancer factor 1, whose expression is regulated by leukemia inhibitory factor (LIF) and bone morphogenetic protein. Removal of LIF, along with addition of Wnt3a, stimulated Cdx2 expression and induced formation of trophoblast stem (TS) cells. These TS cells were able to differentiate into cells with characteristics of spongiotrophoblast and trophoblast giant cells. This is, to our knowledge, the first evidence that TE lineage differentiation can be induced by Wnt signaling in mouse ES cells. PMID:18192238

  19. Mouse prostate epithelial luminal cells lineage originate in the basal layer where the primitive stem/early progenitor cells reside: implications for identifying prostate cancer stem cells.

    PubMed

    Zhou, Jianjun; Feigenbaum, Lionel; Yee, Carole; Song, Hongbin; Yates, Clayton

    2013-01-01

    Prostate stem cells are thought to be responsible for generation of all prostate epithelial cells and for tissue maintenance. The lineage relationship between basal and luminal cells in the prostate is not well clarified. We developed a mouse model to trace cell fate and a mouse model with a slowly cycling cell label to provide insight into this question. The results obtained indicate that putative mouse prostate stem cells are likely to reside in the basal layer. PMID:23819124

  20. Mouse Prostate Epithelial Luminal Cells Lineage Originate in the Basal Layer Where the Primitive Stem/Early Progenitor Cells Reside: Implications for Identifying Prostate Cancer Stem Cells

    PubMed Central

    Zhou, Jianjun; Feigenbaum, Lionel; Yee, Carole; Song, Hongbin; Yates, Clayton

    2013-01-01

    Prostate stem cells are thought to be responsible for generation of all prostate epithelial cells and for tissue maintenance. The lineage relationship between basal and luminal cells in the prostate is not well clarified. We developed a mouse model to trace cell fate and a mouse model with a slowly cycling cell label to provide insight into this question. The results obtained indicate that putative mouse prostate stem cells are likely to reside in the basal layer. PMID:23819124

  1. Fam40b is required for lineage commitment of murine embryonic stem cells

    PubMed Central

    Wagh, V; Doss, M X; Sabour, D; Niemann, R; Meganathan, K; Jagtap, S; Gaspar, J A; Ardestani, M A; Papadopoulos, S; Gajewski, M; Winkler, J; Hescheler, J; Sachinidis, A

    2014-01-01

    FAM40B (STRIP2) is a member of the striatin-interacting phosphatase and kinase (STRIPAK) complex that is involved in the regulation of various processes such as cell proliferation and differentiation. Its role for differentiation processes in embryonic stem cells (ESCs) is till now completely unknown. Short hairpin RNA (shRNA)-mediated silencing of Fam40b expression in ESCs and differentiating embryoid bodies (EBs) led to perturbed differentiation to embryonic germ layers and their derivatives including a complete abrogation of cardiomyogenesis. Pluripotency factors such as Nanog, Oct4 and Sox2 as well as epigenetic factors such as histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3-β (Dnmt3b) were highly upregulated in Fam40b knockdown EBs as compared with control and scrambled EBs. To examine the relevance of Fam40b for development in vivo, Fam40b was knocked down in developing zebrafish. Morpholino-mediated knockdown of Fam40b led to severe abnormalities of the cardiovascular system, including an impaired expression of ventricular myosin heavy chain (vmhc) and of cardiac myosin light chain 2 (cmlc2) in the heart. We identified the gene product of Fam40b in ESCs as a perinuclear and nucleolar protein with a molecular weight of 96 kDa. We conclude that the expression of Fam40b is essential for the lineage commitment of murine embryonic stem cells (mESCs) into differentiated somatic cells via mechanisms involving pluripotency and epigenetic networks. PMID:25010986

  2. 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. PMID:26064540

  3. 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

  4. Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment

    PubMed Central

    Croes, Michiel; Oner, F. Cumhur; Kruyt, Moyo C.; Blokhuis, Taco J.; Bastian, Okan; Dhert, Wouter J. A.; Alblas, Jacqueline

    2015-01-01

    Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about the osteogenic potential of proinflammatory factors on MSCs. Our goal was to determine the specific conditions allowing the pro-osteogenic effects of distinct inflammatory stimuli. Human bone marrow MSCs were exposed to tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS). Cells were cultured in growth medium or osteogenic differentiation medium. Alternatively, bone morphogenetic protein 2 (BMP-2) was used as osteogenic supplement to simulate the conditions in vivo. Alkaline phosphatase activity and calcium deposition were indicators of osteogenicity. To elucidate lineage commitment-dependent effects, MSCs were pre-differentiated prior treatment. Our results show that TNF-α and LPS do not affect the expression of osteogenic markers by MSCs in the absence of an osteogenic supplement. In osteogenic differentiation medium or together with BMP-2 however, these mediators highly stimulated their alkaline phosphatase activity and subsequent matrix mineralization. In pre-osteoblasts, matrix mineralization was significantly increased by these mediators, but irrespective of the culture conditions. Our study shows that inflammatory factors potently enhance the osteogenic capacity of MSCs. These properties may be harnessed in bone regenerative strategies. Importantly, the commitment of MSCs to the osteogenic lineage greatly enhances their responsiveness to inflammatory signals. PMID:26176237

  5. Limiting dilution analysis of the stem cells for T cell lineage

    SciTech Connect

    Katsura, Y.; Kina, T.; Amagai, T.; Tsubata, T.; Hirayoshi, K.; Takaoki, Y.; Sado, T.; Nishikawa, S.I.

    1986-10-15

    Stem cell activities of bone marrow, spleen, thymus, and fetal liver cells for T cell lineage were studied comparatively by transferring the cells from these organs through i.v. or intrathymus (i.t.) route into right leg- and tail-shielded (L-T-shielded) and 900 R-irradiated recipient mice, which were able to survive without supplying hemopoietic stem cells. Cells from B10.Thy-1.1 (H-2b, Thy-1.1) mice were serially diluted and were transferred into L-T-shielded and irradiated C57BL/6 (H-2b, Thy-1.2) mice, and 21 days later the thymus cells of recipient mice were assayed for Thy-1.1+ cells by flow cytofluorometry. The percentage of recipient mice possessing donor-type T cells was plotted against the number of cells transferred, and the stem cell activity in each cell source was expressed as the 50% positive value, the number of donor cells required for generating donor-type T cells in the thymuses of 50% of recipient mice. In i.v. transfer experiments, the activity of bone marrow cells was similar to that of fetal liver cells, and about 100 times and nearly 1000 times higher than those of spleen cells and thymus cells, respectively. In i.t. transfer experiments, the number of cells required for generating donor-type T cells was much lower than that in i.v. transfer experiments, although the ratio in 50% positive values between i.v. and i.t. transfers differed among cell sources. In i.t. transfers, the 50% positive value of bone marrow cells was five times, 400 times, and 500 times higher than that of fetal liver cells, spleen cells, and thymus cells, respectively. Our previous finding that stem cells are enriched in the spleens of mice which were whole body-irradiated and marrow-reconstituted 7 days earlier was confirmed also by the present limiting dilution assay carried out in i.v. as well as i.t. transfers.

  6. Organizational Metrics of Interchromatin Speckle Factor Domains: Integrative Classifier for Stem Cell Adhesion & Lineage Signaling

    PubMed Central

    Vega, Sebastián L.; Dhaliwal, Anandika; Arvind, Varun; Patel, Parth J.; Beijer, Nick R. M.; de Boer, Jan; Murthy, N. Sanjeeva; Kohn, Joachim; Moghe, Prabhas V.

    2015-01-01

    Stem cell fates on biomaterials are influenced by the complex confluence of microenvironmental cues emanating from soluble growth factors, cell-to-cell contacts, and biomaterial properties. Cell-microenvironment interactions influence the cell fate by initiating a series of outside-in signaling events that traverse from the focal adhesions to the nucleus via the cytoskeleton and modulate the sub-nuclear protein organization and gene expression. Here, we report a novel imaging-based framework that highlights the spatial organization of sub-nuclear proteins, specifically the splicing factor SC-35 in the nucleoplasm, as an integrative marker to distinguish between minute differences of stem cell lineage pathways in response to stimulatory soluble factors, surface topologies, and microscale topographies. This framework involves the high resolution image acquisition of SC-35 domains and imaging-based feature extraction to obtain quantitative nuclear metrics in tandem with machine learning approaches to generate a predictive cell state classification model. The acquired SC-35 metrics led to > 90% correct classification of emergent human mesenchymal stem cell (hMSC) phenotypes in populations of hMSCs exposed for merely 3 days to basal, adipogenic, or osteogenic soluble cues, as well as varying levels of dexamethasone-induced alkaline phosphatase (ALP) expression. Early osteogenic cellular responses across a series of surface patterns, fibrous scaffolds, and micropillars were also detected and classified using this imaging-based methodology. Complex cell states resulting from inhibition of RhoGTPase, β-catenin, and FAK could be classified with > 90% sensitivity on the basis of differences in the SC-35 organizational metrics. This indicates that SC-35 organization is sensitively impacted by adhesion-related signaling molecules that regulate osteogenic differentiation. Our results show that diverse microenvironment cues affect different attributes of the SC-35 organizational metrics and lead to distinct emergent organizational patterns. Taken together, these studies demonstrate that the early organization of SC-35 domains could serve as a “fingerprint” of the intracellular mechanotransductive signaling that governs growth factor- and topography-responsive stem cell states. PMID:25765854

  7. Matrix elasticity perturbation and Lamin-A/C expression in stem cells modulate their mechanics and lineage specification

    NASA Astrophysics Data System (ADS)

    Ivanovska, Irena; Discher, Dennis

    2012-02-01

    Commitment of stem cells to different lineages is regulated by many cues in their local microenvironment. They are particularly sensitive to the mechanical properties of their extracellular matrix. Nuclear lamins are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. In particular Lamin A/C levels could influence cellular mechanical sensitivity. Here we show that perturbation of the extracellular matrix and nucleus mechanics can direct stem cells lineage specification. We studied the behavior of human mensechymal stem cells (hMSC) cultured on thin highly ordered collagen nanofilms. To tune the mechanical properties of the nanofilms we used the enzyme transglutaminase as a crosslinking agent. AFM imaging and manipulation is used to examine the nano topography and mechanical properties of the films and cells. Film stiffening affects cells morphology, cytoskeleton organization and their elastic response. hMSCs cultured for two weeks on collagen nanofilms initially tune their stiffness with matrix elasticity but later continuously change it with time. We observed upregulation of osteogenic markers on cross-linked films and increased lamin A/C expression. We show that manipulating Lamin-A/C expression in stem cells also directs cell lineage with knockdown favoring adipogenesis and over expression favoring osteogenesis. We found positive correlation between matrix and nucleus mechanics and that they have a synergistic effect on hMSCs differentiation potential.

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

    PubMed

    Götz, Magdalena; Sirko, Swetlana; Beckers, Johannes; Irmler, Martin

    2015-08-01

    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. PMID:25965557

  9. 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

  10. IFN-? causes aplastic anemia by altering hematopoietic stem/progenitor cell composition and disrupting lineage differentiation

    PubMed Central

    Karwan, Megan; Saleh, Bahara; Hodge, Deborah L.; Chan, Tim; Boelte, Kimberly C.; Keller, Jonathan R.; Young, Howard A.

    2014-01-01

    Aplastic anemia (AA) is characterized by hypocellular marrow and peripheral pancytopenia. Because interferon gamma (IFN-?) can be detected in peripheral blood mononuclear cells of AA patients, it has been hypothesized that autoreactive T lymphocytes may be involved in destroying the hematopoietic stem cells. We have observed AA-like symptoms in our IFN-? adenylate-uridylaterich element (ARE)deleted (del) mice, which constitutively express a low level of IFN-? under normal physiologic conditions. Because no T-cell autoimmunity was observed, we hypothesized that IFN-? may be directly involved in the pathophysiology of AA. In these mice, we did not detect infiltration of T cells in bone marrow (BM), and the existing T cells seemed to be hyporesponsive. We observed inhibition in myeloid progenitor differentiation despite an increase in serum levels of cytokines involved in hematopoietic differentiation and maturation. Furthermore, there was a disruption in erythropoiesis and B-cell differentiation. The same phenomena were also observed in wild-type recipients of IFN-? ARE-del BM. The data suggest that AA occurs when IFN-? inhibits the generation of myeloid progenitors and prevents lineage differentiation, as opposed to infiltration of activated T cells. These results may be useful in improving treatment as well as maintaining a disease-free status. PMID:25342713

  11. Selective cell targeting and lineage tracing of human induced pluripotent stem cells using recombinant avian retroviruses.

    PubMed

    Hildebrand, Laura; Seemann, Petra; Kurtz, Andreas; Hecht, Jochen; Contzen, Jörg; Gossen, Manfred; Stachelscheid, Harald

    2015-12-01

    Human induced pluripotent stem cells (hiPSC) differentiate into multiple cell types. Selective cell targeting is often needed for analyzing gene function by overexpressing proteins in a distinct population of hiPSC-derived cell types and for monitoring cell fate in response to stimuli. However, to date, this has not been possible, as commonly used viruses enter the hiPSC via ubiquitously expressed receptors. Here, we report for the first time the application of a heterologous avian receptor, the tumor virus receptor A (TVA), to selectively transduce TVA(+) cells in a mixed cell population. Expression of the TVA surface receptor via genetic engineering renders cells susceptible for infection by avian leucosis virus (ALV). We generated hiPSC lines with this stably integrated, ectopic TVA receptor gene that expressed the receptor while retaining pluripotency. The undifferentiated hiPSC(TVA+) as well as their differentiating progeny could be infected by recombinant ALV (so-called RCAS virus) with high efficiency. Due to incomplete receptor blocking, even sequential infection of differentiating or undifferentiated TVA(+) cells was possible. In conclusion, the TVA/RCAS system provides an efficient and gentle gene transfer system for hiPSC and extends our possibilities for selective cell targeting and lineage tracing studies. PMID:26109426

  12. Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation

    PubMed Central

    Farabaugh, Susan M.; Boone, David N.; Lee, Adrian V.

    2015-01-01

    Insulin-like growth factor (IGF) signaling is fundamental for growth and survival. A large body of evidence (laboratory, epidemiological, and clinical) implicates the exploitation of this pathway in cancer. Up to 50% of breast tumors express the activated form of the type 1 insulin-like growth factor receptor (IGF1R). Breast cancers are categorized into subtypes based upon hormone and ERRB2 receptor expression and/or gene expression profiling. Even though IGF1R influences tumorigenic phenotypes and drug resistance across all breast cancer subtypes, it has specific expression and function in each. In some subtypes, IGF1R levels correlate with a favorable prognosis, while in others it is associated with recurrence and poor prognosis, suggesting different actions based upon cellular and molecular contexts. In this review, we examine IGF1R expression and function as it relates to breast cancer subtype and therapy-acquired resistance. Additionally, we discuss the role of IGF1R in stem cell maintenance and lineage differentiation and how these cell fate influences may alter the differentiation potential and cellular composition of breast tumors. PMID:25964777

  13. Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells

    PubMed Central

    Rimmelé, Pauline; Bigarella, Carolina L.; Liang, Raymond; Izac, Brigitte; Dieguez-Gonzalez, Rebeca; Barbet, Gaetan; Donovan, Michael; Brugnara, Carlo; Blander, Julie M.; Sinclair, David A.; Ghaffari, Saghi

    2014-01-01

    Summary Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT)1 is required for homeostatic HSC maintenance. Differentiation of young SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant decline in the lymphoid compartment, anemia, and altered expression of associated genes. Combined with HSC accumulation of damaged DNA and expression patterns of age-linked molecules, these have striking overlaps with aged HSCs. We further show that SIRT1 controls HSC homeostasis via the longevity transcription factor FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and lineage specification. They also indicate that SIRT1 might contribute to delaying HSC aging. PMID:25068121

  14. Dinosaur Tracks and Traces

    NASA Astrophysics Data System (ADS)

    Gillette, David D.; Lockley, Martin G.

    1991-02-01

    The study of fossilized dinosaur remains, vertebrate paleontology is a well established discipline, but the discovery and rediscovery of numerous and varied dinosaur footprints and nest sites has spurred a renaissance in the associated field of ichnological research. Dinosaur Tracks and Traces is the first book ever to be devoted to this subject, and it represents the work of seventy noted dinosaur ichnologists. Contributors address the history of science and the relevance of dinosaur ichnology to the interpretation of dinosaur behaviour, paleoecology, paleoenvironments, and evolution. Several new preservation, conservation, and documentation techniques are also presented. The book is richly illustrated and is intended for students and professionals in the areas of paleontology, vertebrate zoology, geology, and paleoenvironmental analysis. The historical aspects of the book and the many site descriptions also make Dinosaur Tracks and Traces appealing to amateur fossil collectors and dinosaur enthusiasts.

  15. 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)

  16. 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)

  17. Stress-Induced Enzyme Activation Primes Murine Embryonic Stem Cells to Differentiate Toward the First Extraembryonic Lineage

    PubMed Central

    Slater, Jill A.; Zhou, Sichang; Puscheck, Elizabeth Ella

    2014-01-01

    Extracellular stresses influence transcription factor (TF) expression and therefore lineage identity in the peri-implantation mouse embryo and its stem cells. This potentially affects pregnancy outcome. To understand the effects of stress signaling during this critical period of pregnancy, we exposed cultured murine embryonic stem cells (mESCs) to hyperosmotic stress. We then measured stress-enzyme-dependent regulation of key pluripotency and lineage TFs. Hyperosmotic stress slowed mESC accumulation due to slowing of the cell cycle over 72 h, after a small apoptotic response within 12 h. Phosphoinositide 3-kinase (PI3K) enzymatic signaling was responsible for stem cell survival under stressed conditions. Stress initially triggered mESC differentiation after 4 h through MEK1, c-Jun N-terminal kinase (JNK), and PI3K enzymatic signaling, which led to proteasomal degradation of Oct4, Nanog, Sox2, and Rex1 TF proteins. Concurrent with this post-transcriptional effect was the decreased accumulation of potency TF mRNA transcripts. After 12–24 h of stress, cells adapted, cell cycle resumed, and Oct4 and Nanog mRNA and protein expression returned to approximately normal levels. The TF protein recovery was mediated by p38MAPK and PI3K signaling, as well as by MEK2 and/or MEK1. However, due to JNK signaling, Rex1 expression did not recover. Probing for downstream lineages revealed that although mESCs did not differentiate morphologically during 24 h of stress, they were primed to differentiate by upregulating markers of the first lineage differentiating from mESCs, extraembryonic endoderm. Thus, although two to three TFs that mark pluripotency recover expression by 24 h of stress, there is nonetheless sustained Rex1 suppression and a priming of mESCs for differentiation to the earliest lineage. PMID:25144240

  18. Specific lineage-priming of bone marrow mesenchymal stem cells provides the molecular framework for their plasticity.

    PubMed

    Delorme, Bruno; Ringe, Jochen; Pontikoglou, Charalampos; Gaillard, Julien; Langonné, Alain; Sensebé, Luc; Noël, Danièle; Jorgensen, Christian; Häupl, Thomas; Charbord, Pierre

    2009-05-01

    Lineage-priming is a molecular model of stem cell (SC) differentiation in which proliferating SCs express a subset of genes associated to the differentiation pathways to which they can commit. This concept has been developed for hematopoietic SCs, but has been poorly studied for other SC populations. Because the differentiation potential of human bone marrow mesenchymal stem cells (BM MSCs) remains controversial, we have explored the theory of lineage-priming applied to these cells. We show that proliferating primary layers and clones of BM MSCs have precise priming to the osteoblastic (O), chondrocytic (C), adipocytic (A), and the vascular smooth muscle (V) lineages, but not to skeletal muscle, cardiac muscle, hematopoietic, hepatocytic, or neural lineages. Priming was shown both at the mRNA (300 transcripts were evaluated) and the protein level. In particular, the master transactivator proteins PPARG, RUNX2, and SOX9 were coexpressed before differentiation induction in all cells from incipient clones. We further show that MSCs cultured in the presence of inducers differentiate into the lineages for which they are primed. Our data point out to a number of signaling pathways that might be activated in proliferating MSCs and would be responsible for the differentiation and proliferation potential of these cells. Our results extend the notion of lineage-priming and provide the molecular framework for inter-A, -O, -C, -V plasticity of BM MSCs. Our data highlight the use of BM MSCs for the cell therapy of skeletal or vascular disorders, but provide a word of caution about their use in other clinical indications. PMID:19418444

  19. 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,…

  20. 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,

  1. The Lineage Specification of Mesenchymal Stem Cells Is Directed by the Rate of Fluid Shear Stress.

    PubMed

    Lu, Juan; Fan, Yijuan; Gong, Xiaoyuan; Zhou, Xin; Yi, Caixia; Zhang, Yinxing; Pan, Jun

    2016-08-01

    The effective regulation of fluid shear stress (FSS) on the lineage specification of mesenchymal stem cells (MSCs) remains to be addressed. We hypothesized that when MSCs are recruited to musculoskeletal system following stimulation, their differentiation into osteogenic or chondrogenic cells is directed by the rate of FSS (ΔSS) through modulation of the mechanosensitive, cation-selective channels (MSCCs), intracellular calcium levels, and F-actin. To this end, MSCs were exposed to laminar FSS linearly increased from 0 to 10 dyn/cm(2) in 0, 2, or 20 min and maintained at 10 dyn/cm(2) for a total of 20 min (termed as ΔSS 0-0', 0-2', and 0-20', respectively, representing more physiological (0-0') and non-physiological (0-2' and 0-20') ΔSS treatments). Our results showed 0-0' facilitated MSC differentiation towards chondrogenic and not osteogenic phenotype, by promoting moderate intracellular calcium concentration ([Ca(2+) ]i ) increase from the calcium channels with the exception of MSCCs or intracellular calcium stores, and F-actin organization. In contrast, 0-2' promoted MSCs towards osteogenic and not chondrogenic phenotype, by inducing significant [Ca(2+) ]i increase mainly from the MSCCs, and F-actin assembly. However, 0-20' elicited the modest osteogenic and chondrogenic phenotypes, as it induced the lowest [Ca(2+) ]i increase mainly from MSCCs, and F-actin assembly. Our results suggest that compared to the more physiological ΔSS, the non-physiological ΔSS favors [Ca(2+) ]i influx from MSCCs. An appropriate non-physiological ΔSS (0-2') even elicits a large [Ca(2+) ]i influx from the MSCCs that reverses the lineage specification of MSCs, providing validation for the high mechanosensitivity of MSCs and guidance for training osteoporosis and osteoarthritis patients. J. Cell. Physiol. 231: 1752-1760, 2016. © 2015 Wiley Periodicals, Inc. PMID:26636289

  2. Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human hematopoietic stem cell differentiation towards erythroid lineage.

    PubMed

    Samet, Imen; Villareal, Myra O; Motojima, Hideko; Han, Junkyu; Sayadi, Sami; Isoda, Hiroko

    2015-06-01

    The generation of blood cellular components from hematopoietic stem cells is important for the therapy of a broad spectrum of hematological disorders. In recent years, several lines of evidence suggested that certain nutrients, vitamins and flavonoids may have important roles in controlling the stem cell fate decision by maintaining their self-renewal or stimulating the lineage-specific differentiation. In this study, main olive leaf phytochemicals oleuropein (Olp), apigenin 7-glucoside (Api7G) and luteolin 7-glucoside (Lut7G) were investigated for their potential effects on hematopoietic stem cell differentiation using both phenotypic and molecular analysis. Oleuropein and the combination of the three compounds enhanced the differentiation of CD34+ cells into myelomonocytic cells and lymphocytes progenitors and inhibited the commitment to megakaryocytic and erythroid lineages. Treatment with Lut7G stimulated both the erythroid and the myeloid differentiation, while treatment with Api7G specifically induced the differentiation of CD34+ cells towards the erythroid lineage and inhibited the myeloid differentiation. Erythroid differentiation induced by Api7G and Lut7G treatments was confirmed by the increase in hemoglobin genes expressions (α-hemoglobin, β-hemoglobin and γ-hemoglobin) and erythroid transcription factor GATA1 expression. As revealed by microarray analysis, the mechanisms underlying the erythroid differentiation-inducing effect of Api7G on hematopoietic stem cells involves the activation of JAK/STAT signaling pathway. These findings prove the differentiation-inducing effects of olive leaf compounds on hematopoietic stem cells and highlight their potential use in the ex vivo generation of blood cells. PMID:26299581

  3. Metabolic Biomarkers of Prenatal Alcohol Exposure in Human Embryonic Stem Cell-derived Neural Lineages

    PubMed Central

    Palmer, Jessica A.; Poenitzsch, Ashley M.; Smith, Susan M.; Conard, Kevin R.; West, Paul R.; Cezar, Gabriela G.

    2012-01-01

    Background Fetal alcohol spectrum disorders (FASD) are a leading cause of neurodevelopmental disability. The mechanisms underlying FASD are incompletely understood, and biomarkers to identify those at risk are lacking. Here, we perform metabolomic analysis of embryoid bodies and neural lineages derived from human embryonic stem (hES) cell to identify the neural secretome produced in response to ethanol exposure. Methods WA01 and WA09 hES cells were differentiated into embryoid bodies, neural progenitors or neurons. Cells along this progression were cultured for four days with 0%, 0.1% or 0.3% ethanol. Supernatants were subjected to C18 chromatography followed by ESI-QTOF-MS. Features were annotated using public databases and the identities of four putative biomarkers were confirmed with purified standards and comparative MS/MS. Results Ethanol treatment induced statistically significant changes to metabolite abundance in human embryoid bodies (180 features), neural progenitors (76 features) and neurons (42 features). There were no shared significant features between different cell types. Fifteen features showed a dose-response to ethanol. Four chemical identities were confirmed; L-thyroxine, 5’-methylthioadenosine, and the tryptophan metabolites L-kynurenine, and indoleacetaldehyde. One feature with a putative annotation of succinyladenosine was significantly increased in both ethanol treatments. Additional features were selective to ethanol treatment but were not annotated in public databases. Conclusions Ethanol exposure induces statistically significant changes to the metabolome profile of human embryoid bodies, neural progenitors and neurons. Several of these metabolites are normally present in human serum, suggesting their usefulness as potential serum FASD biomarkers. These findings suggest the biochemical pathways that are affected by ethanol in the developing nervous system and delineate mechanisms of alcohol injury during human development. PMID:22324771

  4. Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells.

    PubMed

    Rivera-Mulia, Juan Carlos; Buckley, Quinton; Sasaki, Takayo; Zimmerman, Jared; Didier, Ruth A; Nazor, Kristopher; Loring, Jeanne F; Lian, Zheng; Weissman, Sherman; Robins, Allan J; Schulz, Thomas C; Menendez, Laura; Kulik, Michael J; Dalton, Stephen; Gabr, Haitham; Kahveci, Tamer; Gilbert, David M

    2015-08-01

    Duplication of the genome in mammalian cells occurs in a defined temporal order referred to as its replication-timing (RT) program. RT changes dynamically during development, regulated in units of 400-800 kb referred to as replication domains (RDs). Changes in RT are generally coordinated with transcriptional competence and changes in subnuclear position. We generated genome-wide RT profiles for 26 distinct human cell types, including embryonic stem cell (hESC)-derived, primary cells and established cell lines representing intermediate stages of endoderm, mesoderm, ectoderm, and neural crest (NC) development. We identified clusters of RDs that replicate at unique times in each stage (RT signatures) and confirmed global consolidation of the genome into larger synchronously replicating segments during differentiation. Surprisingly, transcriptome data revealed that the well-accepted correlation between early replication and transcriptional activity was restricted to RT-constitutive genes, whereas two-thirds of the genes that switched RT during differentiation were strongly expressed when late replicating in one or more cell types. Closer inspection revealed that transcription of this class of genes was frequently restricted to the lineage in which the RT switch occurred, but was induced prior to a late-to-early RT switch and/or down-regulated after an early-to-late RT switch. Analysis of transcriptional regulatory networks showed that this class of genes contains strong regulators of genes that were only expressed when early replicating. These results provide intriguing new insight into the complex relationship between transcription and RT regulation during human development. PMID:26055160

  5. Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells

    PubMed Central

    Rivera-Mulia, Juan Carlos; Buckley, Quinton; Sasaki, Takayo; Zimmerman, Jared; Didier, Ruth A.; Nazor, Kristopher; Loring, Jeanne F.; Lian, Zheng; Weissman, Sherman; Robins, Allan J.; Schulz, Thomas C.; Menendez, Laura; Kulik, Michael J.; Dalton, Stephen; Gabr, Haitham; Kahveci, Tamer; Gilbert, David M.

    2015-01-01

    Duplication of the genome in mammalian cells occurs in a defined temporal order referred to as its replication-timing (RT) program. RT changes dynamically during development, regulated in units of 400–800 kb referred to as replication domains (RDs). Changes in RT are generally coordinated with transcriptional competence and changes in subnuclear position. We generated genome-wide RT profiles for 26 distinct human cell types, including embryonic stem cell (hESC)-derived, primary cells and established cell lines representing intermediate stages of endoderm, mesoderm, ectoderm, and neural crest (NC) development. We identified clusters of RDs that replicate at unique times in each stage (RT signatures) and confirmed global consolidation of the genome into larger synchronously replicating segments during differentiation. Surprisingly, transcriptome data revealed that the well-accepted correlation between early replication and transcriptional activity was restricted to RT-constitutive genes, whereas two-thirds of the genes that switched RT during differentiation were strongly expressed when late replicating in one or more cell types. Closer inspection revealed that transcription of this class of genes was frequently restricted to the lineage in which the RT switch occurred, but was induced prior to a late-to-early RT switch and/or down-regulated after an early-to-late RT switch. Analysis of transcriptional regulatory networks showed that this class of genes contains strong regulators of genes that were only expressed when early replicating. These results provide intriguing new insight into the complex relationship between transcription and RT regulation during human development. PMID:26055160

  6. 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. PMID:25694098

  7. Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages.

    PubMed

    Ucar, Ahmet; Ucar, Olga; Klug, Paula; Matt, Sonja; Brunk, Fabian; Hofmann, Thomas G; Kyewski, Bruno

    2014-08-21

    Within the thymus, two major thymic epithelial cell (TEC) subsets-cortical and medullary TECs-provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed "thymospheres"). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness. PMID:25148026

  8. Nonplantigrade Foot Posture: A Constraint on Dinosaur Body Size

    PubMed Central

    Kubo, Tai; Kubo, Mugino O.

    2016-01-01

    Dinosaurs had functionally digitigrade or sub-unguligrade foot postures. With their immediate ancestors, dinosaurs were the only terrestrial nonplantigrades during the Mesozoic. Extant terrestrial mammals have different optimal body sizes according to their foot posture (plantigrade, digitigrade, and unguligrade), yet the relationship of nonplantigrade foot posture with dinosaur body size has never been investigated, even though the body size of dinosaurs has been studied intensively. According to a large dataset presented in this study, the body sizes of all nonplantigrades (including nonvolant dinosaurs, nonvolant terrestrial birds, extant mammals, and extinct Nearctic mammals) are above 500 g, except for macroscelid mammals (i.e., elephant shrew), a few alvarezsauroid dinosaurs, and nondinosaur ornithodirans (i.e., the immediate ancestors of dinosaurs). When nonplantigrade tetrapods evolved from plantigrade ancestors, lineages with nonplantigrade foot posture exhibited a steady increase in body size following Cope’s rule. In contrast, contemporaneous plantigrade lineages exhibited no trend in body size evolution and were largely constrained to small body sizes. This evolutionary pattern of body size specific to foot posture occurred repeatedly during both the Mesozoic and the Cenozoic eras. Although disturbed by the end-Cretaceous extinction, species of mid to large body size have predominantly been nonplantigrade animals from the Jurassic until the present; conversely, species with small body size have been exclusively composed of plantigrades in the nonvolant terrestrial tetrapod fauna. PMID:26790003

  9. Nonplantigrade Foot Posture: A Constraint on Dinosaur Body Size.

    PubMed

    Kubo, Tai; Kubo, Mugino O

    2016-01-01

    Dinosaurs had functionally digitigrade or sub-unguligrade foot postures. With their immediate ancestors, dinosaurs were the only terrestrial nonplantigrades during the Mesozoic. Extant terrestrial mammals have different optimal body sizes according to their foot posture (plantigrade, digitigrade, and unguligrade), yet the relationship of nonplantigrade foot posture with dinosaur body size has never been investigated, even though the body size of dinosaurs has been studied intensively. According to a large dataset presented in this study, the body sizes of all nonplantigrades (including nonvolant dinosaurs, nonvolant terrestrial birds, extant mammals, and extinct Nearctic mammals) are above 500 g, except for macroscelid mammals (i.e., elephant shrew), a few alvarezsauroid dinosaurs, and nondinosaur ornithodirans (i.e., the immediate ancestors of dinosaurs). When nonplantigrade tetrapods evolved from plantigrade ancestors, lineages with nonplantigrade foot posture exhibited a steady increase in body size following Cope's rule. In contrast, contemporaneous plantigrade lineages exhibited no trend in body size evolution and were largely constrained to small body sizes. This evolutionary pattern of body size specific to foot posture occurred repeatedly during both the Mesozoic and the Cenozoic eras. Although disturbed by the end-Cretaceous extinction, species of mid to large body size have predominantly been nonplantigrade animals from the Jurassic until the present; conversely, species with small body size have been exclusively composed of plantigrades in the nonvolant terrestrial tetrapod fauna. PMID:26790003

  10. Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila

    PubMed Central

    Zhao, Shaowei; Geng, Qing; Gao, Yu; Li, Xin; Zhang, Yang; Wang, Zhaohui

    2014-01-01

    In regenerative tissues, one of the strategies to protect stem cells from genetic aberrations, potentially caused by frequent cell division, is to transiently expand the stem cell daughters before further differentiation. However, failure to exit the transit amplification may lead to overgrowth, and the molecular mechanism governing this regulation remains vague. In a Drosophila mutagenesis screen for factors involved in the regulation of germline stem cell (GSC) lineage, we isolated a mutation in the gene CG32364, which encodes a putative RNA-binding protein (RBP) and is designated as tumorous testis (tut). In tut mutant, spermatogonia fail to differentiate and over-amplify, a phenotype similar to that in mei-P26 mutant. Mei-P26 is a TRIM-NHL tumor suppressor homolog required for the differentiation of GSC lineage. We found that Tut binds preferentially a long isoform of mei-P26 3′UTR, and is essential for the translational repression of mei-P26 reporter. Bam and Bgcn are both RBPs that have also been shown to repress mei-P26 expression. Our genetic analyses indicate that tut, bam, or bgcn is required to repress mei-P26 and to promote the differentiation of GSCs. Biochemically, we demonstrate that Tut, Bam, and Bgcn can form a physical complex in which Bam holds Tut on its N-terminus and Bgcn on its C-terminus. Our in vivo and in vitro evidence illustrate that Tut acts with Bam, Bgcn to accurately coordinate proliferation and differentiation in Drosophila germline stem cell lineage. PMID:25412508

  11. Three RNA binding proteins form a complex to promote differentiation of germline stem cell lineage in Drosophila.

    PubMed

    Chen, Di; Wu, Chan; Zhao, Shaowei; Geng, Qing; Gao, Yu; Li, Xin; Zhang, Yang; Wang, Zhaohui

    2014-11-01

    In regenerative tissues, one of the strategies to protect stem cells from genetic aberrations, potentially caused by frequent cell division, is to transiently expand the stem cell daughters before further differentiation. However, failure to exit the transit amplification may lead to overgrowth, and the molecular mechanism governing this regulation remains vague. In a Drosophila mutagenesis screen for factors involved in the regulation of germline stem cell (GSC) lineage, we isolated a mutation in the gene CG32364, which encodes a putative RNA-binding protein (RBP) and is designated as tumorous testis (tut). In tut mutant, spermatogonia fail to differentiate and over-amplify, a phenotype similar to that in mei-P26 mutant. Mei-P26 is a TRIM-NHL tumor suppressor homolog required for the differentiation of GSC lineage. We found that Tut binds preferentially a long isoform of mei-P26 3'UTR, and is essential for the translational repression of mei-P26 reporter. Bam and Bgcn are both RBPs that have also been shown to repress mei-P26 expression. Our genetic analyses indicate that tut, bam, or bgcn is required to repress mei-P26 and to promote the differentiation of GSCs. Biochemically, we demonstrate that Tut, Bam, and Bgcn can form a physical complex in which Bam holds Tut on its N-terminus and Bgcn on its C-terminus. Our in vivo and in vitro evidence illustrate that Tut acts with Bam, Bgcn to accurately coordinate proliferation and differentiation in Drosophila germline stem cell lineage. PMID:25412508

  12. Synaptically-Competent Neurons Derived from Canine Embryonic Stem Cells by Lineage Selection with EGF and Noggin

    PubMed Central

    Wilcox, Jared T.; Lai, Jonathan K. Y.; Semple, Esther; Brisson, Brigitte A.; Gartley, Cathy; Armstrong, John N.; Betts, Dean H.

    2011-01-01

    Pluripotent stem cell lines have been generated in several domestic animal species; however, these lines traditionally show poor self-renewal and differentiation. Using canine embryonic stem cell (cESC) lines previously shown to have sufficient self-renewal capacity and potency, we generated and compared canine neural stem cell (cNSC) lines derived by lineage selection with epidermal growth factor (EGF) or Noggin along the neural default differentiation pathway, or by directed differentiation with retinoic acid (RA)-induced floating sphere assay. Lineage selection produced large populations of SOX2+ neural stem/progenitor cell populations and neuronal derivatives while directed differentiation produced few and improper neuronal derivatives. Primary canine neural lines were generated from fetal tissue and used as a positive control for differentiation and electrophysiology. Differentiation of EGF- and Noggin-directed cNSC lines in N2B27 with low-dose growth factors (BDNF/NT-3 or PDGFαα) produced phenotypes equivalent to primary canine neural cells including 3CB2+ radial progenitors, MOSP+ glia restricted precursors, VIM+/GFAP+ astrocytes, and TUBB3+/MAP2+/NFH+/SYN+ neurons. Conversely, induction with RA and neuronal differentiation produced inadequate putative neurons for further study, even though appropriate neuronal gene expression profiles were observed by RT-PCR (including Nestin, TUBB3, PSD95, STX1A, SYNPR, MAP2). Co-culture of cESC-derived neurons with primary canine fetal cells on canine astrocytes was used to test functional maturity of putative neurons. Canine ESC-derived neurons received functional GABAA- and AMPA-receptor mediated synaptic input, but only when co-cultured with primary neurons. This study presents established neural stem/progenitor cell populations and functional neural derivatives in the dog, providing the proof-of-concept required to translate stem cell transplantation strategies into a clinically relevant animal model. PMID:21611190

  13. Dinosaur energetics: setting the bounds on feasible physiologies and ecologies.

    PubMed

    Clarke, Andrew

    2013-09-01

    The metabolic status of dinosaurs has long been debated but remains unresolved as no consistent picture has emerged from a range of anatomical and isotopic evidence. Quantitative analysis of dinosaur energetics, based on general principles applicable to all vertebrates, shows that many features of dinosaur lifestyle are compatible with a physiology similar to that of extant lizards, scaled up to dinosaur body masses and temperatures. The analysis suggests that sufficient metabolic scope would have been available to support observed dinosaur growth rates and allow considerable locomotor activity, perhaps even migration. Since at least one dinosaur lineage evolved true endothermy, this study emphasizes there was no single dinosaur physiology. Many small theropods were insulated with feathers and appear to have been partial or full endotherms. Uninsulated small taxa, and all juveniles, presumably would have been ectothermic, with consequent diurnal and seasonal variations in body temperature. In larger taxa, inertial homeothermy would have resulted in warm and stable body temperatures but with a basal metabolism significantly below that of extant mammals or birds of the same size. It would appear that dinosaurs exhibited a range of metabolic levels to match the broad spectrum of ecological niches they occupied. PMID:23933721

  14. Enhanced Generation of Myeloid Lineages in Hematopoietic Differentiation from Embryonic Stem Cells by Silencing Transcriptional Repressor Twist-2

    PubMed Central

    Sharabi, Andrew B.; Lee, Sung-Hyung; Goodell, Margaret A.; Huang, Xue F.

    2009-01-01

    Abstract The self-renewal and multilineage differentiation of embryonic stem cells (ESC) is largely governed by transcription factors or repressors. Extensive efforts have focused on elucidating critical factors that control the differentiation of specific cell lineages, for instance, myeloid lineages in hematopoietic development. In this study, we found that Twist-2, a basic helix-loop-helix (bHLH) transcription factor, plays a critical role in inhibiting the differentiation of ESC. Murine ES cells, in which Twist-2 expression is silenced by lentivirally delivered shRNA, exhibit an enhanced formation of primary embryoid bodies (EB) and enhanced differentiation into mesodermally derived hematopoietic colonies. Furthermore, Twist-2 silenced (LV-siTwist-2) ESC display significantly increased generation of myeloid lineages (Gr-1+ and F4/80+ cells) during in vitro hematopoietic differentiation. Treatment with the Toll-like receptor (TLR) 4 ligand synergistically stimulates the generation of primary EB formation as well as of hematopoietic progenitors differentiated from LV-siTwist-2 ES cells. Thus, this study reveals the critical role of the transcriptional repressor Twist-2 in regulating the development of myeloid lineage in hematopoietic differentiation from ESC. This study also suggests a potential strategy for directional differentiation of ESC by inhibiting a transcriptional repressor. PMID:20025523

  15. Notch-mediated suppression of TSC2 expression regulates cell differentiation in the Drosophila intestinal stem cell lineage.

    PubMed

    Kapuria, Subir; Karpac, Jason; Biteau, Benoit; Hwangbo, DaeSung; Jasper, Heinrich

    2012-01-01

    Epithelial homeostasis in the posterior midgut of Drosophila is maintained by multipotent intestinal stem cells (ISCs). ISCs self-renew and produce enteroblasts (EBs) that differentiate into either enterocytes (ECs) or enteroendocrine cells (EEs) in response to differential Notch (N) activation. Various environmental and growth signals dynamically regulate ISC activity, but their integration with differentiation cues in the ISC lineage remains unclear. Here we identify Notch-mediated repression of Tuberous Sclerosis Complex 2 (TSC2) in EBs as a required step in the commitment of EBs into the EC fate. The TSC1/2 complex inhibits TOR signaling, acting as a tumor suppressor in vertebrates and regulating cell growth. We find that TSC2 is expressed highly in ISCs, where it maintains stem cell identity, and that N-mediated repression of TSC2 in EBs is required and sufficient to promote EC differentiation. Regulation of TSC/TOR activity by N signaling thus emerges as critical for maintenance and differentiation in somatic stem cell lineages. PMID:23144631

  16. Micropatterning Extracellular Matrix Proteins on Electrospun Fibrous Substrate Promote Human Mesenchymal Stem Cell Differentiation Toward Neurogenic Lineage.

    PubMed

    Li, Huaqiong; Wen, Feng; Chen, Huizhi; Pal, Mintu; Lai, Yuekun; Zhao, Allan Zijian; Tan, Lay Poh

    2016-01-13

    In this study, hybrid micropatterned grafts constructed via a combination of microcontact printing and electrospinning techniques process were utilized to investigate the influencing of patterning directions on human mesenchymal stem cells (hMSCs) differentiation to desired phenotypes. We found that the stem cells could align and elongate along the direction of the micropattern, where they randomly distributed on nonmicropatterned surfaces. Concomitant with patterning effect of component on stem cell alignment, a commensurate increase on the expression of neural lineage commitment markers, such as microtubule associated protein 2 (MAP2), Nestin, NeuroD1, and Class III β-Tubulin, were revealed from mRNA expression by quantitative Real Time PCR (qRT-PCR) and MAP2 expression by immunostaining. In addition, the effect of electrospun fiber orientation on cell behaviors was further examined. An angle of 45° between the direction of micropatterning and orientation of aligned fibers was verified to greatly prompt the outgrowth of filopodia and neurogenesis of hMSCs. This study demonstrates that the significance of hybrid components and electrospun fiber alignment in modulating cellular behavior and neurogenic lineage commitment of hMSCs, suggesting promising application of porous scaffolds with smart component and topography engineering in clinical regenerative medicine. PMID:26654444

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

    SciTech Connect

    Chow, Paik Wah; Abdul Hamid, Zariyantey; Chan, Kok Meng; Inayat-Hussain, Salmaan Hussain; Rajab, Nor Fadilah

    2015-04-01

    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-forming 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 progenitors. • 1,4-BQ toxicity is greater in single- than multilineage committed progenitors.

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

    SciTech Connect

    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.

  19. Induced Pluripotent Stem Cells Can Effectively Differentiate into Multiple Functional Lymphocyte Lineages In Vivo with Negligible Bias.

    PubMed

    Lan, Tianshu; Wang, Libin; Xu, Lin; Jin, Ning; Yan, Guoliang; Xia, Junjie; Wang, Hailong; Zhuang, Guohong; Gao, Chang; Meng, Luxi; Du, Feifei; Zhou, Qi; Qi, Zhongquan

    2016-03-15

    Lymphohematopoietic stem cells (L-HSCs) generated from self-somatic cell-derived induced pluripotent stem cells (iPSCs) are a potential source of cells for the treatment of hematological disorders. However, the generation of truly functional L-HSCs from iPSCs has yet to be achieved. Thus, whether iPSCs have the inherent potential to generate a normal differentiated phenotype and functional population of multiple lineages of terminally differentiated lymphocytes needs to be assessed. Here, we used tetraploid embryo complementation to provide a normal environment for the differentiation of hematopoietic cells from iPSCs and embryonic stem cells (ESCs). We then evaluated the characteristics, populations, and functions of lymphocytes derived from iPSCs, ESCs, and naïve isogenic C57BL/6 mice. The results showed that iPSC-derived lymphocytes (iPSLs) expressed normal levels of major histocompatibility complex-I (MHC-I) and exhibited a fully pluripotent capacity to differentiate into CD4(+) T, CD8(+) T, regulatory T, B, and natural killer cells. Following in vitro stimulation with either concanavalin A or an alloantigen, iPSLs exhibited the same capacities for proliferation and cytokine secretion as ESC-derived or isogenic lymphocytes. Furthermore, iPSC-derived bone marrow cells could differentiate into multiple lymphocyte lineages that reconstituted the lymphocyte population in syngeneic lethally irradiated recipient animals. Our results demonstrated that iPSCs have the inherent potential to differentiate into multiple lineages of functional lymphocytes without bias, and further support the practical application of iPSC-based treatments to hematological disorders. PMID:26715393

  20. In vitro differentiation of human parthenogenetic stem cells into neural lineages.

    PubMed

    Isaev, Dmitry A; Garitaonandia, Ibon; Abramihina, Tatiana V; Zogovic-Kapsalis, Tatjana; West, Richard A; Semechkin, Andrey Y; Müller, Albrecht M; Semechkin, Ruslan A

    2012-01-01

    Human parthenogenetic stem cells are derived from the inner cell mass of blastocysts obtained from unfertilized oocytes that have been stimulated to develop without any participation of male gamete. As parthenogenesis does not involve the destruction of a viable human embryo, the derivation and use of human parthenogenetic stem cells does not raise the same ethical concerns as conventional embryonic stem cells. Human parthenogenetic stem cells are similar to embryonic stem cells in their proliferation and multilineage in vitro differentiation capacity. The aim of this study is to derive multipotent neural stem cells from human parthenogenetic stem cells that are stable to passaging and cryopreservation, and have the ability to further differentiate into functional neurons. Immunocytochemistry, quantitative real-time PCR, or FACS were used to confirm that the derived neural stem cells express neural markers such as NES, SOX2 and MS1. The derived neural stem cells keep uniform morphology for at least 30 passages and can be spontaneously differentiated into cells with neuron morphology that express TUBB3 and MAP2, and fire action potentials. These results suggest that parthenogenetic stem cells are a very promising and potentially unlimited source for the derivation of multipotent neural stem cells that can be used for therapeutic applications. PMID:22168496

  1. Differentiation of human gingival mesenchymal stem cells into neuronal lineages in 3D bioconjugated injectable protein hydrogel construct for the management of neuronal disorder.

    PubMed

    Rao, Suresh Ranga; Subbarayan, Rajasekaran; Dinesh, Murugan Girija; Arumugam, Gnanamani; Raja, Selvaraj Thirupathi Kumara

    2016-01-01

    The success of regeneration attempt is based on an ideal combination of stem cells, scaffolding and growth factors. Tissue constructs help to maintain stem cells in a required area for a desired time. There is a need for easily obtainable cells, potentially autologous stem cells and a biologically acceptable scaffold for use in humans in different difficult situations. This study aims to address these issues utilizing a unique combination of stem cells from gingiva and a hydrogel scaffold, based on a natural product for regenerative application. Human gingival mesenchymal stem cells (HGMSCs) were, with due induction, differentiated to neuronal lineages to overcome the problems associated with birth tissue-related stem cells. The differentiation potential of neuronal lineages was confirmed with suitable specific markers. The properties of mesenchymal stem cells in encapsulated form were observed to be similar to free cells. The encapsulated cells (3D) were then subjected to differentiation into neuronal lineages with suitable inducers, and the morphology and gene expression of transient cells were analyzed. HGMSCs was differentiated into neuronal lineages as both free and encapsulated forms without any significant differences. The presence of Nissl bodies and the neurite outgrowth confirm the differentiation. The advantages of this new combination appear to make it a promising tissue construct for translational application. PMID:26869025

  2. Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing.

    PubMed

    Otsuka, Kensuke; Iwasaki, Toshiyasu

    2015-07-01

    An understanding of the dynamics of intestinal Lgr5(+) stem cells is important for elucidating the mechanism of colonic cancer development. We previously established a method for evaluating Lgr5(+) stem cells by tamoxifen-dependent Lgr5-lineage tracing and showed that high-dose-rate radiation stimulated replenishment of colonic stem cells. In this study, we evaluated the effects of low-dose-rate radiation on stem cell maintenance. Tamoxifen (4OHT)-injected Lgr5-EGFP-IRES-Cre(ERT2) × ROSA-LSL-LacZ mice were used, LacZ-labeled colonic crypts were enumerated, and the loss of LacZ(+) crypts under low-dose-rate radiation was estimated. After 4OHT treatment, the number of LacZ-labeled Lgr5(+) stem cells was higher in the colon of infant mice than in adult mice. The percentage of LacZ-labeled crypts in infant mice rapidly decreased after 4OHT treatment. However, the percentage of labeled crypts plateaued at ∼2% at 4 weeks post-treatment and remained unchanged for up to 7 months. Thus, it will be advantageous to evaluate the long-term effects of low-dose-rate radiation. Next, we determined the percentages of LacZ-labeled crypts irradiated with 1 Gy administered at different dose rates. As reported in our previous study, mice exposed to high-dose-rate radiation (30 Gy/h) showed a marked replenishment (P = 0.04). However, mice exposed to low-dose-rate radiation (0.003 Gy/h) did not exhibit accelerated stem-cell replenishment (P = 0.47). These findings suggest the percentage of labeled crypts can serve as a useful indicator of the effects of dose rate on the stem cell pool. PMID:25832104

  3. Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing

    PubMed Central

    Otsuka, Kensuke; Iwasaki, Toshiyasu

    2015-01-01

    An understanding of the dynamics of intestinal Lgr5+ stem cells is important for elucidating the mechanism of colonic cancer development. We previously established a method for evaluating Lgr5+ stem cells by tamoxifen-dependent Lgr5-lineage tracing and showed that high-dose-rate radiation stimulated replenishment of colonic stem cells. In this study, we evaluated the effects of low-dose-rate radiation on stem cell maintenance. Tamoxifen (4OHT)-injected Lgr5-EGFP-IRES-CreERT2 × ROSA-LSL-LacZ mice were used, LacZ-labeled colonic crypts were enumerated, and the loss of LacZ+ crypts under low-dose-rate radiation was estimated. After 4OHT treatment, the number of LacZ-labeled Lgr5+ stem cells was higher in the colon of infant mice than in adult mice. The percentage of LacZ-labeled crypts in infant mice rapidly decreased after 4OHT treatment. However, the percentage of labeled crypts plateaued at ∼2% at 4 weeks post-treatment and remained unchanged for up to 7 months. Thus, it will be advantageous to evaluate the long-term effects of low-dose-rate radiation. Next, we determined the percentages of LacZ-labeled crypts irradiated with 1 Gy administered at different dose rates. As reported in our previous study, mice exposed to high-dose-rate radiation (30 Gy/h) showed a marked replenishment (P = 0.04). However, mice exposed to low-dose-rate radiation (0.003 Gy/h) did not exhibit accelerated stem-cell replenishment (P = 0.47). These findings suggest the percentage of labeled crypts can serve as a useful indicator of the effects of dose rate on the stem cell pool. PMID:25832104

  4. Notch Lineages and Activity in Intestinal Stem Cells Determined by a New Set of Knock-In Mice

    PubMed Central

    Fre, Silvia; Hannezo, Edouard; Sale, Sanja; Huyghe, Mathilde; Lafkas, Daniel; Kissel, Holger; Louvi, Angeliki; Greve, Jeffrey; Louvard, Daniel; Artavanis-Tsakonas, Spyros

    2011-01-01

    The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFPSAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues. PMID:21991352

  5. Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs).

    PubMed

    Saraswati, Sarika; Deskins, Desirae L; Holt, Ginger E; Young, Pampee P

    2012-01-01

    We and others have found that Wnt signaling inhibition is important in mesenchymal stem cell (MSC) self-renewal. Pyrvinium was identified as a potent Wnt inhibitor in a chemical screen for small molecules. In the present study, we hypothesized that pyrvinium will enhance MSC self-renewal to improve the clinical efficacy of MSC therapy. Pyrvinium increased MSC proliferation in vitro while inhibiting their osteogenic and chondrogenic lineage commitment by reducing cytoplasmic ?-catenin. Although MSCs are a promising target for cell therapy, strategies to enhance their survival and maintain their stemness in the wounded area are essential. Using an in vivo model of granulation tissue formation, we demonstrated that pyrvinium enhanced long-term MSC engraftment. Pyrvinium-treated MSC-generated granulation tissue also demonstrated less ectopic differentiation into bone or cartilage. This study highlights the potential of using a therapeutic Wnt inhibitor to enhance MSC-driven regenerative therapy. PMID:22332749

  6. A novel human artificial chromosome vector provides effective cell lineage-specific transgene expression in human mesenchymal stem cells.

    PubMed

    Ren, Xianying; Katoh, Motonobu; Hoshiya, Hidetoshi; Kurimasa, Akihiro; Inoue, Toshiaki; Ayabe, Fumiaki; Shibata, Kotaro; Toguchida, Junya; Oshimura, Mitsuo

    2005-01-01

    Mesenchymal stem cells (MSCs) hold promise for use in adult stem cell-mediated gene therapy. One of the major aims of stem cell-mediated gene therapy is to develop vectors that will allow appropriate levels of expression of therapeutic genes along differentiation under physiological regulation of the specialized cells. Human artificial chromosomes (HACs) are stably maintained as independent chromosomes in host cells and should be free from potential insertional mutagenesis problems of conventional transgenes. Therefore, HACs have been proposed as alternative implements to cell-mediated gene therapy. Previously, we constructed a novel HAC, termed 21 Deltapq HAC, with a loxP site in which circular DNA can be reproducibly inserted by the Cre/loxP system. We here assessed the feasibility of lineage-specific transgene expression by the 21Deltapq HAC vector using an in vitro differentiation system with an MSC cell line, hiMSCs, which has potential for osteogenic, chondrogenic, and adipogenic differentiation. An enhanced green fluorescent protein (EGFP) gene driven by a promoter for osteogenic lineage-specific osteopontin (OPN) gene was inserted onto the 21 Deltapq HAC and then transferred into hiMSC. The expression cassette was flanked by the chicken HS4 insulators to block promoter interference from adjacent drug-resistant genes. The EGFP gene was specifically expressed in the hiMSC that differentiated into osteocytes in coordination with the transcription of endogenous OPN gene but was not expressed after adipogenic differentiation induction or in noninduction culture. These results suggest that use of the HAC vector is suitable for regulated expression of transgenes in stem cell-mediated gene therapy. PMID:16141362

  7. A sauropodomorph dinosaur from the Upper Triassic (Carman) of southern Brazil

    NASA Astrophysics Data System (ADS)

    Langer, Max C.; Abdala, Fernando; Richter, Martha; Benton, Michael J.

    1999-10-01

    Three newly discovered skeletons from the Carnian red beds of the Santa Maria Formation, south Brazil, represent one of the oldest dinosaurs ever found. The new taxon Saturnalia tupiniquim, is equivalent in age to the earliest dinosaurs from northwestern Argentina, being the oldest sauropodomorph dinosaur known from plentiful skeletal material. The record of Saturnalia, a 1.5-m-long gracile plant-eating animal, indicates that, like other major dinosaur lineages, the first representatives of the mainly heavy-built sauropodomorphs were gracile animals.

  8. The WNT-controlled transcriptional regulator LBH is required for mammary stem cell expansion and maintenance of the basal lineage

    PubMed Central

    Lindley, Linsey E.; Curtis, Kevin M.; Sanchez-Mejias, Avencia; Rieger, Megan E.; Robbins, David J.; Briegel, Karoline J.

    2015-01-01

    The identification of multipotent mammary stem cells (MaSCs) has provided an explanation for the unique regenerative capacity of the mammary gland throughout adult life. However, it remains unclear what genes maintain MaSCs and control their specification into the two epithelial lineages: luminal and basal. LBH is a novel transcription co-factor in the WNT pathway with hitherto unknown physiological function. LBH is expressed during mammary gland development and aberrantly overexpressed in aggressive ‘basal’ subtype breast cancers. Here, we have explored the in vivo role of LBH in mammopoiesis. We show that in postnatal mammary epithelia, LBH is predominantly expressed in the Lin−CD29highCD24+ basal MaSC population. Upon conditional inactivation of LBH, mice exhibit pronounced delays in mammary tissue expansion during puberty and pregnancy, accompanied by increased luminal differentiation at the expense of basal lineage specification. These defects could be traced to a severe reduction in the frequency and self-renewal/differentiation potential of basal MaSCs. Mechanistically, LBH induces expression of key epithelial stem cell transcription factor ΔNp63 to promote a basal MaSC state and repress luminal differentiation genes, mainly that encoding estrogen receptor α (Esr1/ERα). Collectively, these studies identify LBH as an essential regulator of basal MaSC expansion/maintenance, raising important implications for its potential role in breast cancer pathogenesis. PMID:25655704

  9. RhoA determines lineage fate of mesenchymal stem cells by modulating CTGF–VEGF complex in extracellular matrix

    PubMed Central

    Li, Changjun; Zhen, Gehua; Chai, Yu; Xie, Liang; Crane, Janet L.; Farber, Emily; Farber, Charles R.; Luo, Xianghang; Gao, Peisong; Cao, Xu; Wan, Mei

    2016-01-01

    Mesenchymal stem cells (MSCs) participate in the repair/remodelling of many tissues, where MSCs commit to different lineages dependent on the cues in the local microenvironment. Here we show that TGFβ-activated RhoA/ROCK signalling functions as a molecular switch regarding the fate of MSCs in arterial repair/remodelling after injury. MSCs differentiate into myofibroblasts when RhoA/ROCK is turned on, endothelial cells when turned off. The former is pathophysiologic resulting in intimal hyperplasia, whereas the latter is physiological leading to endothelial repair. Further analysis revealed that MSC RhoA activation promotes formation of an extracellular matrix (ECM) complex consisting of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). Inactivation of RhoA/ROCK in MSCs induces matrix metalloproteinase-3-mediated CTGF cleavage, resulting in VEGF release and MSC endothelial differentiation. Our findings uncover a novel mechanism by which cell–ECM interactions determine stem cell lineage specificity and offer additional molecular targets to manipulate MSC-involved tissue repair/regeneration. PMID:27126736

  10. BMP Signaling and Its pSMAD1/5 Target Genes Differentially Regulate Hair Follicle Stem Cell Lineages

    PubMed Central

    Genander, Maria; Cook, Peter J.; Ramskld, Daniel; Keyes, Brice E.; Mertz, Aaron F.; Sandberg, Rickard; Fuchs, Elaine

    2014-01-01

    Hair follicle stem cells (HFSCs) and their transit amplifying cell (TAC) progeny sense BMPs at defined stages of the hair cycle to control their proliferation and differentiation. Here, we exploit the distinct spatial and temporal localizations of these cells to selectively ablate BMP signaling in each compartment and examine its functional role. We find that BMP signaling is required for HFSC quiescence and to promote TAC differentiation along different lineages as the hair cycle progresses. We also combine in vivo genome-wide chromatin immunoprecipitation and deep-sequencing, transcriptional profiling, and loss-of-function genetics to define BMP-regulated genes. We show that some pSMAD1/5 targets, like Gata3, function specifically in TAC lineage-progression. Others, like Id1 and Id3, function in both HFSCs and TACs, but in distinct ways. Our study therefore illustrates the complex differential roles that a key signaling pathway can play in regulation of closely-related stem/progenitor cells within the context of their overall niche. PMID:25312496

  11. Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells.

    PubMed

    Wheldon, Lee M; Abakir, Abdulkadir; Ferjentsik, Zoltan; Dudnakova, Tatiana; Strohbuecker, Stephanie; Christie, Denise; Dai, Nan; Guan, Shengxi; Foster, Jeremy M; Corra, Ivan R; Loose, Matthew; Dixon, James E; Sottile, Virginie; Johnson, Andrew D; Ruzov, Alexey

    2014-06-12

    5-Methylcytosine (5mC) is an epigenetic modificationinvolved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised from DNA by thymine-DNA glycosylase (TDG) followed by regeneration of unmodified cytosine via the base excision repair pathway. Despite evidence that this mechanism is operative in embryonic stem cells, the role of TDG-dependent demethylation in differentiation and development is currently unclear. Here, we demonstrate that widespread oxidation of 5hmC to 5caC occurs in postimplantation mouse embryos. We show that 5fC and 5caC are transiently accumulated during lineage specification of neural stem cells (NSCs) in culture and invivo. Moreover, 5caC is enriched at the cell-type-specific promoters during differentiation of NSCs, and TDG knockdown leads to increased 5fC/5caC levels in differentiating NSCs. Our data suggest that active demethylation contributes to epigenetic reprogramming determining lineage specification in embryonic brain. PMID:24882006

  12. 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

  13. 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…

  14. 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.

  15. 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. PMID:26763699

  16. mTORC2 regulates mechanically induced cytoskeletal reorganization and lineage selection in marrow derived mesenchymal stem cells

    PubMed Central

    Sen, Buer; Xie, Zhihui; Case, Natasha; Thompson, William R.; Uzer, Gunes; Styner, Maya; Rubin, Janet

    2013-01-01

    The cell cytoskeleton interprets and responds to physical cues from the microenvironment. Applying mechanical force to mesenchymal stem cells induces formation of a stiffer cytoskeleton, which biases against adipogenic differentiation and toward osteoblastogenesis. mTORC2, the mTOR complex defined by its binding partner rictor, is implicated in resting cytoskeletal architecture and is activated by mechanical force. We asked if mTORC2 played a role in mechanical adaptation of the cytoskeleton. We found that during bi-axial strain induced cytoskeletal restructuring, mTORC2 and Akt co-localize with newly assembled focal adhesions (FA). Disrupting the function of mTORC2, or that of its downstream substrate Akt, prevented mechanically-induced F-actin stress fiber development. mTORC2 becomes associated with vinculin during strain, and knock-down of vinculin prevents mTORC2 activation. In contrast, mTORC2 is not recruited to the FA complex during its activation by insulin, nor does insulin alter cytoskeletal structure. Further, when rictor was knocked down, the ability of MSC to enter the osteoblastic lineage was reduced, and when cultured in adipogenic medium, rictor-deficient MSC showed accelerated adipogenesis. This indicated that cytoskeletal remodeling promotes osteogenesis over adipogenesis. In sum, our data show that mTORC2 is involved in stem cell responses to biophysical stimuli, regulating both signaling and cytoskeletal reorganization. As such, mechanical activation of mTORC2 signaling participates in mesenchymal stem cell lineage selection, preventing adipogenesis by preserving β-catenin and stimulating osteogenesis by generating a stiffer cytoskeleton. PMID:23821483

  17. 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. PMID:24926017

  18. Derivation of male germ cell-like lineage from human fetal bone marrow stem cells.

    PubMed

    Hua, Jinlian; Pan, Shaohui; Yang, Chunrong; Dong, Wuzi; Dou, Zhongying; Sidhu, Kuldip S

    2009-07-01

    Mesenchymal stem cells derived from bone marrow are a well characterized population of adult stem cells that can be maintained and propagated in culture for a long time with the capacity to form a variety of cell types. Reports have shown that murine and human embryonic stem cells can differentiate into primordial germ cells and then to early gametes. Evidence has indicated that some adult stem cells also have the potential to differentiate into germ cells. Currently, there are no reports on directed differentiation of human mesenchymal stem cells into germ cells. This study investigated the ability of retinoic acid and testicular extracts to induce human bone marrow stem cells (hBMSC) to differentiate into male germ cells. It was found that a small population of hBMSC seem to transdifferentiate into male germ cell-like cells. These cells expressed early germ cell markers OCT4, STELLA, NANOG and VASA, and male germ-ceil-specific markers such as DAZL, TH2, c-kit, beta(1)-integrin, ACR, PRMl, FSHR, STRA8 and SCP3, as analysed by reverse transcription-polymerase chain reaction and immunohistochemistry. These results demonstrated that hBMSC may differentiate into male germ cells and the same could be used as a potential source of cells for reproductive toxicological studies. PMID:19573297

  19. 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.

  20. Ethanol Diverts Early Neuronal Differentiation Trajectory of Embryonic Stem Cells by Disrupting the Balance of Lineage Specifiers

    PubMed Central

    Sánchez-Alvarez, Rosa; Gayen, Saurabh; Vadigepalli, Rajanikanth; Anni, Helen

    2013-01-01

    Background Ethanol is a toxin responsible for the neurodevelopmental deficits of Fetal Alcohol Spectrum Disorders (FASD). Recent evidence suggests that ethanol modulates the protein expression of lineage specifier transcription factors Oct4 (Pou5f1) and Sox2 in early stages of mouse embryonic stem (ES) cell differentiation. We hypothesized that ethanol induced an imbalance in the expression of Oct4 and Sox2 in early differentiation, that dysregulated the expression of associated and target genes and signaling molecules and diverted cells from neuroectodermal (NE) formation. Methodology/Principal Findings We showed modulation by ethanol of 33 genes during ES cell differentiation, using high throughput microfluidic dynamic array chips measuring 2,304 real time quantitative PCR assays. Based on the overall gene expression dynamics, ethanol drove cells along a differentiation trajectory away from NE fate. These ethanol-induced gene expression changes were observed as early as within 2 days of differentiation, and were independent of cell proliferation or apoptosis. Gene expression changes were correlated with fewer βIII-tubulin positive cells of an immature neural progenitor phenotype, as well as a disrupted actin cytoskeleton were observed. Moreover, Tuba1a and Gapdh housekeeping genes were modulated by ethanol during differentiation and were replaced by a set of ribosomal genes with stable expression. Conclusions/Significance These findings provided an ethanol-response gene signature and pointed to the transcriptional dynamics underlying lineage imbalance that may be relevant to FASD phenotype. PMID:23724002

  1. Specific Preferences in Lineage Choice and Phenotypic Plasticity of Glioma Stem Cells Under BMP4 and Noggin Influence.

    PubMed

    Videla Richardson, Guillermo Agustín; Garcia, Carolina Paola; Roisman, Alejandro; Slavutsky, Irma; Fernandez Espinosa, Damián Darío; Romorini, Leonardo; Miriuka, Santiago Gabriel; Arakaki, Naomi; Martinetto, Horacio; Scassa, María Elida; Sevlever, Gustavo Emilio

    2016-01-01

    Although BMP4-induced differentiation of glioma stem cells (GSCs) is well recognized, details of the cellular responses triggered by this morphogen are still poorly defined. In this study, we established several GSC-enriched cell lines (GSC-ECLs) from high-grade gliomas. The expansion of these cells as adherent monolayers, and not as floating neurospheres, enabled a thorough study of the phenotypic changes that occurred during their differentiation. Herein, we evaluated GSC-ECLs' behavior toward differentiating conditions by depriving them of growth factors and/or by adding BMP4 at different concentrations. After analyzing cellular morphology, proliferation and lineage marker expression, we determined that GSC-ECLs have distinct preferences in lineage choice, where some of them showed an astrocyte fate commitment and others a neuronal one. We found that this election seems to be dictated by the expression pattern of BMP signaling components present in each GSC-ECL. Additionally, treatment of GSC-ECLs with the BMP antagonist, Noggin, also led to evident phenotypic changes. Interestingly, under certain conditions, some GSC-ECLs adopted an unexpected smooth muscle-like phenotype. As a whole, our findings illustrate the wide differentiation potential of GSCs, highlighting their molecular complexity and paving a way to facilitate personalized differentiating therapies. PMID:25808628

  2. Phenotypic analysis and isolation of murine hematopoietic stem cells and lineage-committed progenitors.

    PubMed

    Frascoli, Michela; Proietti, Michele; Grassi, Fabio

    2012-01-01

    The bone marrow is the principal site where HSCs and more mature blood cells lineage progenitors reside and differentiate in an adult organism. HSCs constitute a minute cell population of pluripotent cells capable of generating all blood cell lineages for a life-time(1). The molecular dissection of HSCs homeostasis in the bone marrow has important implications in hematopoiesis, oncology and regenerative medicine. We describe the labeling protocol with fluorescent antibodies and the electronic gating procedure in flow cytometry to score hematopoietic progenitor subsets and HSCs distribution in individual mice (Fig. 1). In addition, we describe a method to extensively enrich hematopoietic progenitors as well as long-term (LT) and short term (ST) reconstituting HSCs from pooled bone marrow cell suspensions by magnetic enrichment of cells expressing c-Kit. The resulting cell preparation can be used to sort selected subsets for in vitro and in vivo functional studies (Fig. 2). Both trabecular osteoblasts(2,3) and sinusoidal endothelium(4) constitute functional niches supporting HSCs in the bone marrow. Several mechanisms in the osteoblastic niche, including a subset of N-cadherin(+) osteoblasts(3) and interaction of the receptor tyrosine kinase Tie2 expressed in HSCs with its ligand angiopoietin-1(5) concur in determining HSCs quiescence. "Hibernation" in the bone marrow is crucial to protect HSCs from replication and eventual exhaustion upon excessive cycling activity(6). Exogenous stimuli acting on cells of the innate immune system such as Toll-like receptor ligands(7) and interferon-?(6) can also induce proliferation and differentiation of HSCs into lineage committed progenitors. Recently, a population of dormant mouse HSCs within the lin(- )c-Kit(+ )Sca-1(+ )CD150(+ )CD48(- )CD34(-) population has been described(8). Sorting of cells based on CD34 expression from the hematopoietic progenitors-enriched cell suspension as described here allows the isolation of both quiescent self-renewing LT-HSCs and ST-HSCs(9). A similar procedure based on depletion of lineage positive cells and sorting of LT-HSC with CD48 and Flk2 antibodies has been previously described(10). In the present report we provide a protocol for the phenotypic characterization and ex vivo cell cycle analysis of hematopoietic progenitors, which can be useful for monitoring hematopoiesis in different physiological and pathological conditions. Moreover, we describe a FACS sorting procedure for HSCs, which can be used to define factors and mechanisms regulating their self-renewal, expansion and differentiation in cell biology and signal transduction assays as well as for transplantation. PMID:22805770

  3. Perivascular Human Endometrial Mesenchymal Stem Cells Express Pathways Relevant to Self-Renewal, Lineage Specification, and Functional Phenotype1

    PubMed Central

    Spitzer, Trimble L.B.; Rojas, Angela; Zelenko, Zara; Aghajanova, Lusine; Erikson, David W.; Barragan, Fatima; Meyer, Michelle; Tamaresis, John S.; Hamilton, Amy E.; Irwin, Juan C.; Giudice, Linda C.

    2011-01-01

    ABSTRACT Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)+/PDGFRB+ (eMSC), MCAM (CD146)−/PDGFRB+ (fibroblast), and MCAM (CD146)+/PDGFRB− (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast. PMID:22075475

  4. Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype.

    PubMed

    Spitzer, Trimble L B; Rojas, Angela; Zelenko, Zara; Aghajanova, Lusine; Erikson, David W; Barragan, Fatima; Meyer, Michelle; Tamaresis, John S; Hamilton, Amy E; Irwin, Juan C; Giudice, Linda C

    2012-02-01

    Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)(+)/PDGFRB(+) (eMSC), MCAM (CD146)(-)/PDGFRB(+) (fibroblast), and MCAM (CD146)(+)/PDGFRB(-) (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast. PMID:22075475

  5. 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.

  6. Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence?

    PubMed Central

    Dor, Natalie J.; Hill, Robert E.; Collinson, J. Martin; West, John D.

    2015-01-01

    The limbal epithelial stem cell (LESC) hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC) hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks. PMID:26554513

  7. The origin and early evolution of dinosaurs.

    PubMed

    Langer, Max C; Ezcurra, Martin D; Bittencourt, Jonathas S; Novas, Fernando E

    2010-02-01

    The oldest unequivocal records of Dinosauria were unearthed from Late Triassic rocks (approximately 230 Ma) accumulated over extensional rift basins in southwestern Pangea. The better known of these are Herrerasaurus ischigualastensis, Pisanosaurus mertii, Eoraptor lunensis, and Panphagia protos from the Ischigualasto Formation, Argentina, and Staurikosaurus pricei and Saturnalia tupiniquim from the Santa Maria Formation, Brazil. No uncontroversial dinosaur body fossils are known from older strata, but the Middle Triassic origin of the lineage may be inferred from both the footprint record and its sister-group relation to Ladinian basal dinosauromorphs. These include the typical Marasuchus lilloensis, more basal forms such as Lagerpeton and Dromomeron, as well as silesaurids: a possibly monophyletic group composed of Mid-Late Triassic forms that may represent immediate sister taxa to dinosaurs. The first phylogenetic definition to fit the current understanding of Dinosauria as a node-based taxon solely composed of mutually exclusive Saurischia and Ornithischia was given as "all descendants of the most recent common ancestor of birds and Triceratops". Recent cladistic analyses of early dinosaurs agree that Pisanosaurus mertii is a basal ornithischian; that Herrerasaurus ischigualastensis and Staurikosaurus pricei belong in a monophyletic Herrerasauridae; that herrerasaurids, Eoraptor lunensis, and Guaibasaurus candelariensis are saurischians; that Saurischia includes two main groups, Sauropodomorpha and Theropoda; and that Saturnalia tupiniquim is a basal member of the sauropodomorph lineage. On the contrary, several aspects of basal dinosaur phylogeny remain controversial, including the position of herrerasaurids, E. lunensis, and G. candelariensis as basal theropods or basal saurischians, and the affinity and/or validity of more fragmentary taxa such as Agnosphitys cromhallensis, Alwalkeria maleriensis, Chindesaurus bryansmalli, Saltopus elginensis, and Spondylosoma absconditum. The identification of dinosaur apomorphies is jeopardized by the incompleteness of skeletal remains attributed to most basal dinosauromorphs, the skulls and forelimbs of which are particularly poorly known. Nonetheless, Dinosauria can be diagnosed by a suite of derived traits, most of which are related to the anatomy of the pelvic girdle and limb. Some of these are connected to the acquisition of a fully erect bipedal gait, which has been traditionally suggested to represent a key adaptation that allowed, or even promoted, dinosaur radiation during Late Triassic times. Yet, contrary to the classical "competitive" models, dinosaurs did not gradually replace other terrestrial tetrapods over the Late Triassic. In fact, the radiation of the group comprises at least three landmark moments, separated by controversial (Carnian-Norian, Triassic-Jurassic) extinction events. These are mainly characterized by early diversification in Carnian times, a Norian increase in diversity and (especially) abundance, and the occupation of new niches from the Early Jurassic onwards. Dinosaurs arose from fully bipedal ancestors, the diet of which may have been carnivorous or omnivorous. Whereas the oldest dinosaurs were geographically restricted to south Pangea, including rare ornithischians and more abundant basal members of the saurischian lineage, the group achieved a nearly global distribution by the latest Triassic, especially with the radiation of saurischian groups such as "prosauropods" and coelophysoids. PMID:19895605

  8. IGF1 Promotes Adipogenesis by a Lineage Bias of Endogenous Adipose Stem/Progenitor Cells.

    PubMed

    Hu, Li; Yang, Guodong; Hägg, Daniel; Sun, Guoming; Ahn, Jeffrey M; Jiang, Nan; Ricupero, Christopher L; Wu, June; Rodhe, Christine Hsu; Ascherman, Jeffrey A; Chen, Lili; Mao, Jeremy J

    2015-08-01

    Adipogenesis is essential for soft tissue reconstruction following trauma or tumor resection. We demonstrate that CD31(-)/34(+)/146(-) cells, a subpopulation of the stromal vascular fraction (SVF) of human adipose tissue, were robustly adipogenic. Insulin growth factor-1 (IGF1) promoted a lineage bias towards CD31(-)/34(+)/146(-) cells at the expense of CD31(-)/34(+)/146(+) cells. IGF1 was microencapsulated in poly(lactic-co-glycolic acid) scaffolds and implanted in the inguinal fat pad of C57Bl6 mice. Control-released IGF1 induced remarkable adipogenesis in vivo by recruiting endogenous cells. In comparison with the CD31(-)/34(+)/146(+) cells, CD31(-)/34(+)/146(-) cells had a weaker Wnt/β-catenin signal. IGF1 attenuated Wnt/β-catenin signaling by activating Axin2/PPARγ pathways in SVF cells, suggesting IGF1 promotes CD31(-)/34(+)/146(-) bias through tuning Wnt signal. PPARγ response element (PPRE) in Axin2 promoter was crucial for Axin2 upregulation, suggesting that PPARγ transcriptionally activates Axin2. Together, these findings illustrate an Axin2/PPARγ axis in adipogenesis that is particularly attributable to a lineage bias towards CD31(-)/34(+)/146(-) cells, with implications in adipose regeneration. PMID:26010009

  9. Stem Rust Resistance in Triticum monococcum Germplasm of the Ug99 Lineage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat stem rust, caused by Puccinia graminis f. sp. tritici, has been effectively controlled through the use of genetic resistance. The recently identified race TTKSK (Ug99) possesses virulence to many resistance genes that have been used in wheat breeding worldwide. One strategy to aid breeders in ...

  10. 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.

  11. 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)

  12. 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)

  13. Single-Cell RNA-Seq of Bone Marrow-Derived Mesenchymal Stem Cells Reveals Unique Profiles of Lineage Priming

    PubMed Central

    Freeman, Brian T.; Jung, Jangwook P.; Ogle, Brenda M.

    2015-01-01

    The plasticity and immunomodulatory capacity of mesenchymal stem cells (MSCs) have spurred clinical use in recent years. However, clinical outcomes vary and many ascribe inconsistency to the tissue source of MSCs. Yet unconsidered is the extent of heterogeneity of individual MSCs from a given tissue source with respect to differentiation potential and immune regulatory function. Here we use single-cell RNA-seq to assess the transcriptional diversity of murine mesenchymal stem cells derived from bone marrow. We found genes associated with MSC multipotency were expressed at a high level and with consistency between individual cells. However, genes associated with osteogenic, chondrogenic, adipogenic, neurogenic and vascular smooth muscle differentiation were expressed at widely varying levels between individual cells. Further, certain genes associated with immunomodulation were also inconsistent between individual cells. Differences could not be ascribed to cycles of proliferation, culture bias or other cellular process, which might alter transcript expression in a regular or cyclic pattern. These results support and extend the concept of lineage priming of MSCs and emphasize caution for in vivo or clinical use of MSCs, even when immunomodulation is the goal, since multiple mesodermal (and even perhaps ectodermal) outcomes are a possibility. Purification might enable shifting of the probability of a certain outcome, but is unlikely to remove multilineage potential altogether. PMID:26352588

  14. 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. PMID:24522537

  15. Directed differentiation of induced pluripotent stem cells into chondrogenic lineages for articular cartilage treatment

    PubMed Central

    Lach, Michał; Richter, Magdalena; Pawlicz, Jarosław; Suchorska, Wiktoria M

    2014-01-01

    In recent years, increases in the number of articular cartilage injuries caused by environmental factors or pathological conditions have led to a notable rise in the incidence of premature osteoarthritis. Osteoarthritis, considered a disease of civilization, is the leading cause of disability. At present, standard methods for treating damaged articular cartilage, including autologous chondrocyte implantation or microfracture, are short-term solutions with important side effects. Emerging treatments include the use of induced pluripotent stem cells, a technique that could provide a new tool for treatment of joint damage. However, research in this area is still early, and no optimal protocol for transforming induced pluripotent stem cells into chondrocytes has yet been established. Developments in our understanding of cartilage developmental biology, together with the use of modern technologies in the field of tissue engineering, provide an opportunity to create a complete functional model of articular cartilage. PMID:25383175

  16. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

    SciTech Connect

    Yim, Evelyn K.F.; Pang, Stella W.; Leong, Kam W. . E-mail: kam.leong@duke.edu

    2007-05-15

    Human mesenchymal stem cells (hMSCs) have been shown to trans-differentiate into neuronal-like cells by culture in neuronal induction media, although the mechanism is not well understood. Topography can also influence cellular responses including enhanced differentiation of progenitor cells. As extracellular matrix (ECM) in vivo comprises topography in the nanoscale, we hypothesize that nanotopography could influence stem cell differentiation into specific non-default pathways, such as transdifferentiation of hMSCs. Differentiation and proliferation of hMSCs were studied on nanogratings of 350 nm width. Cytoskeleton and nuclei of hMSCs were aligned and elongated along the nanogratings. Gene profiling and immunostaining showed significant up-regulation of neuronal markers such as microtubule-associated protein 2 (MAP2) compared to unpatterned and micropatterned controls. The combination of nanotopography and biochemical cues such as retinoic acid further enhanced the up-regulation of neuronal marker expressions, but nanotopography showed a stronger effect compared to retinoic acid alone on unpatterned surface. This study demonstrated the significance of nanotopography in directing differentiation of adult stem cells.

  17. REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells

    PubMed Central

    Thakore-Shah, Kaushali; Koleilat, Tasneem; Jan, Majib; John, Alan; Pyle, April D.

    2015-01-01

    REST (RE1 silencing transcription factor), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down’s syndrome and Huntington’s disease. The role of REST/NRSF in control of human embryonic stem cell (hESC) fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture. Interestingly, we have found that altering REST levels in multiple hESC lines does not result in loss of self-renewal but instead leads to increased survival. During differentiation, REST knockdown resulted in increased MAPK/ERK and WNT signaling and increased expression of mesendoderm differentiation markers. Therefore we have uncovered a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells. PMID:26690059

  18. Postnatal stem cell survival: does the niche, a rare harbor where to resist the ebb tide of differentiation, also provide lineage-specific instructions?

    PubMed

    Kindler, Vincent

    2005-10-01

    Postnatal stem cells regulate the homeostasis of the majority of our tissues. They continuously generate new progenitors and mature, functional cells to replace old cells, which cannot assume the tissue function anymore and are eliminated. Blood, skin, gut mucosa, muscle, cartilage, nerves, cornea, retina, liver, and many other structures are regulated by stem cells. As a result of their ability to produce large numbers of functionally mature cells, postnatal stem cells represent a promising tool for regenerative therapy. Indeed, unmanipulated stem cells or their progeny amplified in vitro are already used in some clinical applications to restore the function of injured or genetically deficient tissues. However, despite our cumulating understanding concerning postnatal stem cells, many aspects of their functionality remain unclear. For instance, in most tissues, we cannot reliably define the phenotype of the postnatal stem cells sustaining its survival. We do not know to which extent the environment surrounding the stem cell-the niche-which is a key actor insuring stem cell self-maintenance, is also implicated in the maintenance of stem cell lineage specificity. Moreover, we have to clarify whether postnatal stem cells are capable of undertaking "transdifferentiation", that is, the conversion of one cell type into another under physiological conditions. Answering these questions should help us to draw a more accurate picture of postnatal stem cell biology and should lead to the design of safe, effective therapies. PMID:16199730

  19. Activated charcoal composite biomaterial promotes human embryonic stem cell differentiation toward neuronal lineage.

    PubMed

    Chen, Eric Y T; Wang, Yung-Chen; Mintz, Alexander; Richards, Alan; Chen, Chi-Shuo; Lu, David; Nguyen, Thien; Chin, Wei-Chun

    2012-08-01

    Transplantation of biomaterial scaffolds encasing human embryonic stem cells (hESCs) has been proposed as a clinical therapy for various neurological lesions and disorders. In light of recent developments, artificially synthesized carbon-based biomaterials such as carbon nanotubes and graphene have demonstrated feasibility in supporting stem cell attachment and differentiation. However, the applicability is significantly hampered by evidence of nanotoxic effects on multiple cell types. Thus, an emergent drive for an innovative carbonaceous biomaterial calls for a safer platform with comparable advantageous characteristics. Here, we showed for the first time, a natural coal-based activated charcoal (AC) composite biosubstrate can support and promote neuronal differentiation in hESCs. The bio-friendly AC composite biomatrices resulted in more matured neuron-like cells. Both of axonal length and density were at least twice as long and abundant, respectively, when compared with control groups. A functional assay demonstrated that the derived neuron-like cells responded to depolarization-dependent synaptic recycling and may contain active synapses. In addition, the AC composite substrate can serve to concentrate growth factors and cell adhesion proteins, further encouraging attachment and hESC differentiation. Moreover, the AC composite biomaterial can potentially be economically manufactured as implantable three-dimensional bioscaffolds, facilitating the regeneration of damaged neural and other tissues. PMID:22623371

  20. Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways.

    PubMed

    Fu, Ziwen; Geng, Cuiyun; Wang, Hui; Yang, Zhihao; Weng, Changjiang; Li, Hua; Deng, Lamei; Liu, Luping; Liu, Nan; Ni, Jianquan; Xie, Ting

    2015-11-17

    The central question in stem cell regulation is how the balance between self-renewal and differentiation is controlled at the molecular level. This study uses germline stem cells (GSCs) in the Drosophila ovary to demonstrate that the Drosophila CCR4 homolog Twin is required intrinsically to promote both GSC self-renewal and progeny differentiation. Twin/CCR4 is one of the two catalytic subunits in the highly conserved CCR4-NOT mRNA deadenylase complex. Twin works within the CCR4-NOT complex to intrinsically maintain GSC self-renewal, at least partly by sustaining E-cadherin-mediated GSC-niche interaction and preventing transposable element-induced DNA damage. It promotes GSC progeny differentiation by forming protein complexes with differentiation factors Bam and Bgcn independently of other CCR4-NOT components. Interestingly, Bam can competitively inhibit the association of Twin with Pop2 in the CCR4-NOT complex. Therefore, this study demonstrates that Twin has important intrinsic roles in promoting GSC self-renewal and progeny differentiation by functioning in different protein complexes. PMID:26549449

  1. Isolation, characterization and the multi-lineage differentiation potential of rabbit bone marrow-derived mesenchymal stem cells

    PubMed Central

    Tan, Sik-Loo; Ahmad, Tunku Sara; Selvaratnam, Lakshmi; Kamarul, Tunku

    2013-01-01

    Mesenchymal stem cells (MSCs) are recognized by their plastic adherent ability, fibroblastic-like appearance, expression of specific surface protein markers, and are defined by their ability to undergo multi-lineage differentiation. Although rabbit bone marrow-derived MSCs (rbMSCs) have been used extensively in previous studies especially in translational research, these cells have neither been defined morphologically and ultrastructurally, nor been compared with their counterparts in humans in their multi-lineage differentiation ability. A study was therefore conducted to define the morphology, surface marker proteins, ultrastructure and multi-lineage differentiation ability of rbMSCs. Herein, the primary rbMSC cultures of three adult New Zealand white rabbits (at least 4 months old) were used for three independent experiments. rbMSCs were isolated using the gradient-centrifugation method, an established technique for human MSCs (hMSCs) isolation. Cells were characterized by phase contrast microscopy observation, transmission electron microscopy analysis, reverse transcriptase-polymerase chain reaction (PCR) analysis, immunocytochemistry staining, flow cytometry, alamarBlue assay, histological staining and quantitative (q)PCR analysis. The isolated plastic adherent cells were in fibroblastic spindle-shape and possessed eccentric, irregular-shaped nuclei as well as rich inner cytoplasmic zones similar to that of hMSCs. The rbMSCs expressed CD29, CD44, CD73, CD81, CD90 and CD166, but were negative (or dim positive) for CD34, CD45, CD117 and HLD-DR. Despite having similar morphology and phenotypic expression, rbMSCs possessed significantly larger cell size but had a lower proliferation rate as compared with hMSCs. Using established protocols to differentiate hMSCs, rbMSCs underwent osteogenic, adipogenic and chondrogenic differentiation. Interestingly, differentiated rbMSCs demonstrated higher levels of osteogenic (Runx2) and chondrogenic (Sox9) gene expressions than that of hMSCs (P < 0.05). There was, however, no difference in the adipogenic (Ppar?) expressions between these cell types (P > 0.05). rbMSCs possess similar morphological characteristics to hMSCs, but have a higher potential for osteogenic and chondrogenic differentiation, despite having a lower cell proliferation rate than hMSCs. The characteristics reported here may be used as a comprehensive set of criteria to define or characterize rbMSCs. PMID:23510053

  2. Rise of dinosaurs reveals major body-size transitions are driven by passive processes of trait evolution

    PubMed Central

    Sookias, Roland B.; Butler, Richard J.; Benson, Roger B. J.

    2012-01-01

    A major macroevolutionary question concerns how long-term patterns of body-size evolution are underpinned by smaller scale processes along lineages. One outstanding long-term transition is the replacement of basal therapsids (stem-group mammals) by archosauromorphs, including dinosaurs, as the dominant large-bodied terrestrial fauna during the Triassic (approx. 252–201 million years ago). This landmark event preceded more than 150 million years of archosauromorph dominance. We analyse a new body-size dataset of more than 400 therapsid and archosauromorph species spanning the Late Permian–Middle Jurassic. Maximum-likelihood analyses indicate that Cope's rule (an active within-lineage trend of body-size increase) is extremely rare, despite conspicuous patterns of body-size turnover, and contrary to proposals that Cope's rule is central to vertebrate evolution. Instead, passive processes predominate in taxonomically and ecomorphologically more inclusive clades, with stasis common in less inclusive clades. Body-size limits are clade-dependent, suggesting intrinsic, biological factors are more important than the external environment. This clade-dependence is exemplified by maximum size of Middle–early Late Triassic archosauromorph predators exceeding that of contemporary herbivores, breaking a widely-accepted ‘rule’ that herbivore maximum size greatly exceeds carnivore maximum size. Archosauromorph and dinosaur dominance occurred via opportunistic replacement of therapsids following extinction, but were facilitated by higher archosauromorph growth rates. PMID:22298850

  3. Determining Regulatory Networks Governing the Differentiation of Embryonic Stem Cells to Pancreatic Lineage

    NASA Astrophysics Data System (ADS)

    Banerjee, Ipsita

    2009-03-01

    Knowledge of pathways governing cellular differentiation to specific phenotype will enable generation of desired cell fates by careful alteration of the governing network by adequate manipulation of the cellular environment. With this aim, we have developed a novel method to reconstruct the underlying regulatory architecture of a differentiating cell population from discrete temporal gene expression data. We utilize an inherent feature of biological networks, that of sparsity, in formulating the network reconstruction problem as a bi-level mixed-integer programming problem. The formulation optimizes the network topology at the upper level and the network connectivity strength at the lower level. The method is first validated by in-silico data, before applying it to the complex system of embryonic stem (ES) cell differentiation. This formulation enables efficient identification of the underlying network topology which could accurately predict steps necessary for directing differentiation to subsequent stages. Concurrent experimental verification demonstrated excellent agreement with model prediction.

  4. Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells

    PubMed Central

    Cassady, John P.; D’Alessio, Ana C.; Sarkar, Sovan; Dani, Vardhan S.; Fan, Zi Peng; Ganz, Kibibi; Roessler, Reinhard; Sur, Mriganka; Young, Richard A.; Jaenisch, Rudolf

    2014-01-01

    Summary Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors. PMID:25454632

  5. Birds have paedomorphic dinosaur skulls.

    PubMed

    Bhullar, Bhart-Anjan S; Marugán-Lobón, Jesús; Racimo, Fernando; Bever, Gabe S; Rowe, Timothy B; Norell, Mark A; Abzhanov, Arhat

    2012-07-12

    The interplay of evolution and development has been at the heart of evolutionary theory for more than a century. Heterochrony—change in the timing or rate of developmental events—has been implicated in the evolution of major vertebrate lineages such as mammals, including humans. Birds are the most speciose land vertebrates, with more than 10,000 living species representing a bewildering array of ecologies. Their anatomy is radically different from that of other vertebrates. The unique bird skull houses two highly specialized systems: the sophisticated visual and neuromuscular coordination system allows flight coordination and exploitation of diverse visual landscapes, and the astonishing variations of the beak enable a wide range of avian lifestyles. Here we use a geometric morphometric approach integrating developmental, neontological and palaeontological data to show that the heterochronic process of paedomorphosis, by which descendants resemble the juveniles of their ancestors, is responsible for several major evolutionary transitions in the origin of birds. We analysed the variability of a series of landmarks on all known theropod dinosaur skull ontogenies as well as outgroups and birds. The first dimension of variability captured ontogeny, indicating a conserved ontogenetic trajectory. The second dimension accounted for phylogenetic change towards more bird-like dinosaurs. Basally branching eumaniraptorans and avialans clustered with embryos of other archosaurs, indicating paedomorphosis. Our results reveal at least four paedomorphic episodes in the history of birds combined with localized peramorphosis (development beyond the adult state of ancestors) in the beak. Paedomorphic enlargement of the eyes and associated brain regions parallels the enlargement of the nasal cavity and olfactory brain in mammals. This study can be a model for investigations of heterochrony in evolutionary transitions, illuminating the origin of adaptive features and inspiring studies of developmental mechanisms. PMID:22722850

  6. Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation.

    PubMed

    Andres, Sarah F; Simmons, James G; Mah, Amanda T; Santoro, M Agostina; Van Landeghem, Laurianne; Lund, P Kay

    2013-12-15

    Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the Apc(Min/+) mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in Apc(Min/+) tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells. PMID:24127567

  7. Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

    PubMed Central

    Andres, Sarah F.; Simmons, James G.; Mah, Amanda T.; Santoro, M. Agostina; Van Landeghem, Laurianne; Lund, P. Kay

    2013-01-01

    Summary Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the ApcMin/+ mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in ApcMin/+ tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B∶ IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells. PMID:24127567

  8. Effect of human umbilical cord blood derived lineage negative stem cells transplanted in amyloid-β induced cognitive impaired mice.

    PubMed

    Banik, Avijit; Prabhakar, Sudesh; Kalra, Jasvinder; Anand, Akshay

    2015-09-15

    Alzheimer's disease (AD) is pathologically characterized by extracellular deposition of insoluble amyloid-β (Aβ) plaques and intracellular tangles made up of phosphorylated tau in brain. Several therapeutic approaches are being carried out in animal AD models for testing their safety and efficacy in altering disease pathology and behavioral deficits. Very few studies have examined the effect of human umbilical cord blood (hUCB) derived stem cells in degenerative disease models despite growing number of cord blood banks worldwide. Here we have examined the therapeutic efficacy of hUCB derived lineage negative (Lin -ve) stem cells in alleviating behavioral and neuropathological deficits in a mouse model of cognitive impairment induced by bilateral intrahippocampal injection of Aβ-42. Lin -ve cells were transplanted at two doses (50,000 and 100,000) at the site of injury and examined at 10 and 60 days post transplantation for rescue of memory deficits. These cells were found to ameliorate cognitive impairment in 50,000-60 days and 100,000-10 days groups whereas, 50,000-10 days and 100,000-60 days groups could not exert any significant improvement. Further, mice showing spatial memory improvement were mediated by up-regulation of BDNF, CREB and also by concomitant down regulation of Fas-L in their brain. The transplanted cells were found in the host tissue and survived up to 60 days without expressing markers of neuronal differentiation or reducing Aβ burden in mouse brain. We suggest that these undifferentiated cells could exert neuroprotective effects either through inhibiting apoptosis and/or trophic effects in the brain. PMID:25989508

  9. Housekeeping gene stability influences the quantification of osteogenic markers during stem cell differentiation to the osteogenic lineage.

    PubMed

    Quiroz, Felipe Garcia; Posada, Olga M; Gallego-Perez, Daniel; Higuita-Castro, Natalia; Sarassa, Carlos; Hansford, Derek J; Agudelo-Florez, Piedad; López, Luis E

    2010-04-01

    Real-time reverse transcription PCR (RT-qPCR) relies on a housekeeping or normalizer gene whose expression remains constant throughout the experiment. RT-qPCR is commonly used for characterization of human bone marrow mesenchymal stem cells (hBMSCs). However, to the best of our knowledge, there are no studies validating the expression stability of the genes used as normalizers during hBMSCs differentiation. This work aimed to study the stability of the housekeeping genes beta-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ribosomal protein L13A (RPL13A) during the osteogenic differentiation of hBMSCs. Their stability was evaluated via RT-qPCR in 14 and 20 day differentiation assays to the osteogenic lineage. Different normalization strategies were evaluated to quantify the osteogenic markers collagen type I, bone sialoprotein and osteonectin. Cell differentiation was confirmed via alizarin red staining. The results demonstrated up-regulation of beta-actin with maximum fold changes (MFC) of 4.38. GAPDH and RPL13A were not regulated by osteogenic media after 14 days and presented average fold changes lower than 2 in 20 day cultures. RPL13A (MFC < 2) had a greater stability when normalizing as a function of culture time compared with GAPDH (MFC stem cells characterization via RT-qPCR. PMID:20396946

  10. Housekeeping gene stability influences the quantification of osteogenic markers during stem cell differentiation to the osteogenic lineage

    PubMed Central

    Posada, Olga M.; Gallego-Perez, Daniel; Higuita-Castro, Natalia; Sarassa, Carlos; Hansford, Derek J.; Agudelo-Florez, Piedad; López, Luis E.

    2010-01-01

    Real-time reverse transcription PCR (RT-qPCR) relies on a housekeeping or normalizer gene whose expression remains constant throughout the experiment. RT-qPCR is commonly used for characterization of human bone marrow mesenchymal stem cells (hBMSCs). However, to the best of our knowledge, there are no studies validating the expression stability of the genes used as normalizers during hBMSCs differentiation. This work aimed to study the stability of the housekeeping genes β-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ribosomal protein L13A (RPL13A) during the osteogenic differentiation of hBMSCs. Their stability was evaluated via RT-qPCR in 14 and 20 day differentiation assays to the osteogenic lineage. Different normalization strategies were evaluated to quantify the osteogenic markers collagen type I, bone sialoprotein and osteonectin. Cell differentiation was confirmed via alizarin red staining. The results demonstrated up-regulation of β-actin with maximum fold changes (MFC) of 4.38. GAPDH and RPL13A were not regulated by osteogenic media after 14 days and presented average fold changes lower than 2 in 20 day cultures. RPL13A (MFC < 2) had a greater stability when normalizing as a function of culture time compared with GAPDH (MFC ≤ 2.2), which resulted in expression patterns of the osteogenic markers more consistent with the observed differentiation process. The results suggest that β-actin regulation could be associated with the morphological changes characteristic of hBMSCs osteogenic differentiation, and provide evidence for the superior performance of RPL13A as a normalizer gene in osteogenic differentiation studies of hBMSCs. This work highlights the importance of validating the normalizer genes used for stem cells characterization via RT-qPCR. PMID:20396946

  11. Differentiation of murine embryonic stem cells toward renal lineages by conditioned medium from ureteric bud cells in vitro.

    PubMed

    Ren, Xiaohui; Zhang, Jingya; Gong, Xiaowen; Niu, Xin; Zhang, Xuejin; Chen, Peng; Zhang, Xuejun

    2010-07-01

    The kidney is formed from two tissue populations derived from the intermediate mesoderm, the ureteric bud, and the metanephric mesenchyme. Metanephric mesenchyme is a pluripotent renal stem population, and conversion of renal mesenchyme into epithelia depends on the ureteric bud in vivo and in vitro. Embryonic stem (ES) cells have been induced to differentiate into a broad spectrum of specialized cell types in vitro, including hematopoietic, pancreatic, and neuronal cells. Such ES-derived cells can provide a valuable source of progenitor cells. However, whether ES cells can be stimulated by factors secreted from the fetal renal cells to differentiate into renal precursor cells in vitro has not been reported. In this study, we showed that murine ES cells can give rise to embryoid bodies in the absence of leukemia inhibitory factor. Culture conditions were optimized [6 days, 10 ng/ml activin and 10(-7) M retinoic acid (RA)] to generate maximal mesoderm populations specifically expressing Pax2 and brachyury. Results showed that 72% of the cells were brachyury positive by fluorescent activated cell sorter on Day 6 of EB cell differentiation. Conditioned medium collected from cultures of ureteric bud cells from renal cells of a 13-day-old fetus was added to the culture medium. Mesoderm cells were cultured for up to 10 days before showing expression of renal markers, initiation of nephrogenesis (WT-1 and Pax2), and terminally differentiated renal cell types (POD-1 and E-cadherin). This study suggests that ES cells pre-treated by RA and activin can interact with secreted molecules of the fetal renal cells to specifically differentiate into renal precursor cells. Our results provide an experimental basis for the development of in vitro assays to steer differentiation of ES cells toward renal lineages. PMID:20705585

  12. Dinosaur Eggs and Babies

    NASA Astrophysics Data System (ADS)

    Carpenter, Kenneth; Hirsch, Karl F.; Horner, John R.

    1996-01-01

    In the last couple of decades the study of dinosaur eggs and babies has proved to be one of the most exciting and profitable areas of dinosaur research. This is the first book solely devoted to this topic and reviews, in scientific detail, our present state of knowledge about this exciting area of palaeontology. Chapters in the book discuss all aspects of the science including the occurrence of eggs, nests and baby skeletons, descriptive osteology of juvenile skeletons, comparative histology of juvenile bone, analyses of eggs and egg shells, palaeoenvironments of nesting sites, nesting behaviour and developmental growth of baby dinosaurs. The volume will be an invaluable addition to the book collections of vertebrate palaeontologists and their graduate students.

  13. A novel lineage restricted, pericyte-like cell line isolated from human embryonic stem cells.

    PubMed

    Greenwood-Goodwin, Midori; Yang, Jiwei; Hassanipour, Mohammad; Larocca, David

    2016-01-01

    Pericytes (PCs) are endothelium-associated cells that play an important role in normal vascular function and maintenance. We developed a method comparable to GMP quality protocols for deriving self-renewing perivascular progenitors from the human embryonic stem cell (hESC), line ESI-017. We identified a highly scalable, perivascular progenitor cell line that we termed PC-A, which expressed surface markers common to mesenchymal stromal cells. PC-A cells were not osteogenic or adipogenic under standard differentiation conditions and showed minimal angiogenic support function in vitro. PC-A cells were capable of further differentiation to perivascular progenitors with limited differentiation capacity, having osteogenic potential (PC-O) or angiogenic support function (PC-M), while lacking adipogenic potential. Importantly, PC-M cells expressed surface markers associated with pericytes. Moreover, PC-M cells had pericyte-like functionality being capable of co-localizing with human umbilical vein endothelial cells (HUVECs) and enhancing tube stability up to 6 days in vitro. We have thus identified a self-renewing perivascular progenitor cell line that lacks osteogenic, adipogenic and angiogenic potential but is capable of differentiation toward progenitor cell lines with either osteogenic potential or pericyte-like angiogenic function. The hESC-derived perivascular progenitors described here have potential applications in vascular research, drug development and cell therapy. PMID:27109637

  14. A novel lineage restricted, pericyte-like cell line isolated from human embryonic stem cells

    PubMed Central

    Greenwood-Goodwin, Midori; Yang, Jiwei; Hassanipour, Mohammad; Larocca, David

    2016-01-01

    Pericytes (PCs) are endothelium-associated cells that play an important role in normal vascular function and maintenance. We developed a method comparable to GMP quality protocols for deriving self-renewing perivascular progenitors from the human embryonic stem cell (hESC), line ESI-017. We identified a highly scalable, perivascular progenitor cell line that we termed PC-A, which expressed surface markers common to mesenchymal stromal cells. PC-A cells were not osteogenic or adipogenic under standard differentiation conditions and showed minimal angiogenic support function in vitro. PC-A cells were capable of further differentiation to perivascular progenitors with limited differentiation capacity, having osteogenic potential (PC-O) or angiogenic support function (PC-M), while lacking adipogenic potential. Importantly, PC-M cells expressed surface markers associated with pericytes. Moreover, PC-M cells had pericyte-like functionality being capable of co-localizing with human umbilical vein endothelial cells (HUVECs) and enhancing tube stability up to 6 days in vitro. We have thus identified a self-renewing perivascular progenitor cell line that lacks osteogenic, adipogenic and angiogenic potential but is capable of differentiation toward progenitor cell lines with either osteogenic potential or pericyte-like angiogenic function. The hESC-derived perivascular progenitors described here have potential applications in vascular research, drug development and cell therapy. PMID:27109637

  15. Arthropod phylogeny: onychophoran brain organization suggests an archaic relationship with a chelicerate stem lineage.

    PubMed

    Strausfeld, Nicholas J; Strausfeld, Camilla Mok; Loesel, Rudi; Rowell, David; Stowe, Sally

    2006-08-01

    Neuroanatomical studies have demonstrated that the architecture and organization among neuropils are highly conserved within any order of arthropods. The shapes of nerve cells and their neuropilar arrangements provide robust characters for phylogenetic analyses. Such analyses so far have agreed with molecular phylogenies in demonstrating that entomostracans+malacostracans belong to a clade (Tetraconata) that includes the hexapods. However, relationships among what are considered to be paraphyletic groups or among the stem arthropods have not yet been satisfactorily resolved. The present parsimony analyses of independent neuroarchitectural characters from 27 arthropods and lobopods demonstrate relationships that are congruent with phylogenies derived from molecular studies, except for the status of the Onychophora. The present account describes the brain of the onychophoran Euperipatoides rowelli, demonstrating that the structure and arrangements of its neurons, cerebral neuropils and sensory centres are distinct from arrangements in the brains of mandibulates. Neuroanatomical evidence suggests that the organization of the onychophoran brain is similar to that of the brains of chelicerates. PMID:16822744

  16. Arthropod phylogeny: onychophoran brain organization suggests an archaic relationship with a chelicerate stem lineage

    PubMed Central

    Strausfeld, Nicholas J; Mok Strausfeld, Camilla; Loesel, Rudi; Rowell, David; Stowe, Sally

    2006-01-01

    Neuroanatomical studies have demonstrated that the architecture and organization among neuropils are highly conserved within any order of arthropods. The shapes of nerve cells and their neuropilar arrangements provide robust characters for phylogenetic analyses. Such analyses so far have agreed with molecular phylogenies in demonstrating that entomostracans+malacostracans belong to a clade (Tetraconata) that includes the hexapods. However, relationships among what are considered to be paraphyletic groups or among the stem arthropods have not yet been satisfactorily resolved. The present parsimony analyses of independent neuroarchitectural characters from 27 arthropods and lobopods demonstrate relationships that are congruent with phylogenies derived from molecular studies, except for the status of the Onychophora. The present account describes the brain of the onychophoran Euperipatoides rowelli, demonstrating that the structure and arrangements of its neurons, cerebral neuropils and sensory centres are distinct from arrangements in the brains of mandibulates. Neuroanatomical evidence suggests that the organization of the onychophoran brain is similar to that of the brains of chelicerates. PMID:16822744

  17. GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment

    PubMed Central

    Huang, I-Husan; Hsiao, Cheng-Te; Wu, Jui-Chung; Liu, Ching-Yi; Wang, Yang-Kao; Chen, Yu-Chen; Huang, Chi-Ming; del álamo, Juan C.; Chang, Zee-Fen; Tang, Ming-Jer; Khoo, Kay-Hooi; Kuo, Jean-Cheng

    2014-01-01

    ABSTRACT Focal adhesions (FAs) undergo maturation that culminates in size and composition changes that modulate adhesion, cytoskeleton remodeling and differentiation. Although it is well recognized that stimuli for osteogenesis of mesenchymal stem cells (MSCs) drive FA maturation, actin organization and stress fiber polarization, the extent to which FA-mediated signals regulated by the FA protein composition specifies MSC commitment remains largely unknown. Here, we demonstrate that, upon dexamethasone (osteogenic induction) treatment, guanine nucleotide exchange factor H1 (GEF-H1, also known as Rho guanine nucleotide exchange factor 2, encoded by ARHGEF2) is significantly enriched in FAs. Perturbation of GEF-H1 inhibits FA formation, anisotropic stress fiber orientation and MSC osteogenesis in an actomyosin-contractility-independent manner. To determine the role of GEF-H1 in MSC osteogenesis, we explore the GEF-H1-modulated FA proteome that reveals non-muscle myosin-II heavy chain-B (NMIIB, also known as myosin-10, encoded by MYH10) as a target of GEF-H1 in FAs. Inhibition of targeting NMIIB into FAs suppresses FA formation, stress fiber polarization, cell stiffness and osteogenic commitments in MSCs. Our data demonstrate a role for FA signaling in specifying MSC commitment. PMID:25107365

  18. From weird wonders to stem lineages: the second reclassification of the Burgess Shale fauna.

    PubMed

    Brysse, Keynyn

    2008-09-01

    The Burgess Shale, a set of fossil beds containing the exquisitely preserved remains of marine invertebrate organisms from shortly after the Cambrian explosion, was discovered in 1909, and first brought to widespread popular attention by Stephen Jay Gould in his 1989 bestseller Wonderful life: The Burgess Shale and the nature of history. Gould contrasted the initial interpretation of these fossils, in which they were 'shoehorned' into modern groups, with the first major reexamination begun in the 1960s, when the creatures were perceived as 'weird wonders', possessing unique body plans and unrelated to modern organisms. More recently, a third phase of Burgess Shale studies has arisen, which has not yet been historically examined. This third phase represents a revolutionary new understanding, brought about, I believe, by a change in taxonomic methodology that led to a new perception of the Burgess creatures, and a new way to comprehend their relationships with modern organisms. The adoption of cladistics, and its corollary, the stem group concept, has forged a new understanding of the Burgess Shale ... but has it also changed the questions we are allowed to ask about evolution? PMID:18761282

  19. Extracellular Vesicles Derived from Osteogenically Induced Human Bone Marrow Mesenchymal Stem Cells Can Modulate Lineage Commitment.

    PubMed

    Martins, Margarida; Ribeiro, Diana; Martins, Albino; Reis, Rui Luís; Neves, Nuno Meleiro

    2016-03-01

    The effective osteogenic commitment of human bone marrow mesenchymal stem cells (hBMSCs) is critical for bone regenerative therapies. Extracellular vesicles (EVs) derived from hBMSCs have a regenerative potential that has been increasingly recognized. Herein, the osteoinductive potential of osteogenically induced hBMSC-EVs was examined. hBMSCs secreted negatively charged nanosized vesicles (∼35 nm) with EV-related surface markers. The yield of EVs over 7 days was dependent on an osteogenic stimulus (standard chemical cocktail or RUNX2 cationic-lipid transfection). These EVs were used to sequentially stimulate homotypic uncommitted cells during 7 days, matching the seeding density of EV parent cells, culture time, and stimuli. Osteogenically committed hBMSC-EVs induced an osteogenic phenotype characterized by marked early induction of BMP2, SP7, SPP1, BGLAP/IBSP, and alkaline phosphatase. Both EV groups outperformed the currently used osteoinductive strategies. These data show that naturally secreted EVs can guide the osteogenic commitment of hBMSCs in the absence of other chemical or genetic osteoinductors. PMID:26923821

  20. Extracellular Vesicles Derived from Osteogenically Induced Human Bone Marrow Mesenchymal Stem Cells Can Modulate Lineage Commitment

    PubMed Central

    Martins, Margarida; Ribeiro, Diana; Martins, Albino; Reis, Rui Luís; Neves, Nuno Meleiro

    2016-01-01

    Summary The effective osteogenic commitment of human bone marrow mesenchymal stem cells (hBMSCs) is critical for bone regenerative therapies. Extracellular vesicles (EVs) derived from hBMSCs have a regenerative potential that has been increasingly recognized. Herein, the osteoinductive potential of osteogenically induced hBMSC-EVs was examined. hBMSCs secreted negatively charged nanosized vesicles (∼35 nm) with EV-related surface markers. The yield of EVs over 7 days was dependent on an osteogenic stimulus (standard chemical cocktail or RUNX2 cationic-lipid transfection). These EVs were used to sequentially stimulate homotypic uncommitted cells during 7 days, matching the seeding density of EV parent cells, culture time, and stimuli. Osteogenically committed hBMSC-EVs induced an osteogenic phenotype characterized by marked early induction of BMP2, SP7, SPP1, BGLAP/IBSP, and alkaline phosphatase. Both EV groups outperformed the currently used osteoinductive strategies. These data show that naturally secreted EVs can guide the osteogenic commitment of hBMSCs in the absence of other chemical or genetic osteoinductors. PMID:26923821

  1. Phosphatase and Tensin Homolog Regulates the Pluripotent State and Lineage Fate Choice in Human Embryonic Stem Cells

    PubMed Central

    Alva, Jackelyn A.; Lee, Grace E.; Escobar, Erika E.; Pyle, April D.

    2014-01-01

    Understanding the intrinsic and extrinsic signals that regulate the molecular basis of the pluripotent state may improve our understanding of mammalian embryogenesis, different states of pluripotency, and our ability to tailor lineage differentiation. Although the role of the PI3K/Akt pathway in the self-renewal and maintenance of mESCs is well-established, the specific contribution of the pathway or of its negative regulator, PTEN, in the maintenance of the human pluripotent state is less understood. To explore the PI3K/AKT pathway in human embryonic stem cell (hESC) pluripotency and differentiation, we generated stable PTEN knockdown (KD) hESCs using short hairpin RNA. Similar to mESCs, we found that PTEN KD hESCs have increased self-renewal, cell survival, and proliferation over multiple passages compared to control cells. However, in contrast to mESCs, in vitro, PTEN KD hESCs differentiated inefficiently in directed differentiation assays, in part due to the continued maintenance of OCT4 and NANOG expression. In teratoma assays, PTEN KD hESCs generated tissues from the three germ layers, although with a bias toward neuroectoderm differentiation. These results demonstrate that PTEN is a key regulator of hESC growth and differentiation, and manipulation of this pathway may improve our ability to regulate and understand the pluripotent state. PMID:21948699

  2. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines.

    PubMed

    Ghosheh, Nidal; Olsson, Björn; Edsbagge, Josefina; Küppers-Munther, Barbara; Van Giezen, Mariska; Asplund, Annika; Andersson, Tommy B; Björquist, Petter; Carén, Helena; Simonsson, Stina; Sartipy, Peter; Synnergren, Jane

    2016-01-01

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models. PMID:26949401

  3. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

    PubMed Central

    Ghosheh, Nidal; Olsson, Björn; Edsbagge, Josefina; Küppers-Munther, Barbara; Van Giezen, Mariska; Asplund, Annika; Andersson, Tommy B.; Björquist, Petter; Carén, Helena; Simonsson, Stina; Sartipy, Peter; Synnergren, Jane

    2016-01-01

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models. PMID:26949401

  4. BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells

    PubMed Central

    Gomes Fernandes, Maria; Dries, Ruben; Roost, Matthias S.; Semrau, Stefan; de Melo Bernardo, Ana; Davis, Richard P.; Ramakrishnan, Ramprasad; Szuhai, Karoly; Maas, Elke; Umans, Lieve; Abon Escalona, Vanesa; Salvatori, Daniela; Deforce, Dieter; Van Criekinge, Wim; Huylebroeck, Danny; Mummery, Christine; Zwijsen, An; Chuva de Sousa Lopes, Susana M.

    2015-01-01

    Summary Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower levels of genomic DNA methylation, high expression of 5-methylcytosine hydroxylases Tet1/2 and low levels of DNA methyltransferases Dnmt3a/b. Moreover, naive mESCs, in which the BMP-SMAD reporter transgene was activated, showed higher resistance to differentiation. Using double Smad1;Smad5 knockout mESCs, we showed that BMP-SMAD signaling is dispensable for self-renewal in both naive and ground state. These mutant mESCs were still pluripotent, but they exhibited higher levels of DNA methylation than their wild-type counterparts and had a higher propensity to differentiate. We showed that BMP-SMAD signaling modulates lineage priming in mESCs, by transiently regulating the enzymatic machinery responsible for DNA methylation. PMID:26711875

  5. BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells.

    PubMed

    Gomes Fernandes, Maria; Dries, Ruben; Roost, Matthias S; Semrau, Stefan; de Melo Bernardo, Ana; Davis, Richard P; Ramakrishnan, Ramprasad; Szuhai, Karoly; Maas, Elke; Umans, Lieve; Abon Escalona, Vanesa; Salvatori, Daniela; Deforce, Dieter; Van Criekinge, Wim; Huylebroeck, Danny; Mummery, Christine; Zwijsen, An; Chuva de Sousa Lopes, Susana M

    2016-01-12

    Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower levels of genomic DNA methylation, high expression of 5-methylcytosine hydroxylases Tet1/2 and low levels of DNA methyltransferases Dnmt3a/b. Moreover, naive mESCs, in which the BMP-SMAD reporter transgene was activated, showed higher resistance to differentiation. Using double Smad1;Smad5 knockout mESCs, we showed that BMP-SMAD signaling is dispensable for self-renewal in both naive and ground state. These mutant mESCs were still pluripotent, but they exhibited higher levels of DNA methylation than their wild-type counterparts and had a higher propensity to differentiate. We showed that BMP-SMAD signaling modulates lineage priming in mESCs, by transiently regulating the enzymatic machinery responsible for DNA methylation. PMID:26711875

  6. High Throughput Transcriptome Profiling of Lithium Stimulated Human Mesenchymal Stem Cells Reveals Priming towards Osteoblastic Lineage

    PubMed Central

    Satija, Neeraj Kumar; Sharma, Deepa; Afrin, Farhat; Tripathi, Rajendra P.; Gangenahalli, Gurudutta

    2013-01-01

    Human mesenchymal stem cells (hMSCs) present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been documented in animal models but its effect in humans is not clear. We, therefore, performed high throughput transcriptome analysis of lithium-treated hMSCs to identify altered gene expression and its relevance to osteogenic differentiation. Our results show suppression of proliferation and enhancement of alkaline phosphatase (ALP) activity upon lithium treatment of hMSCs under non-osteogenic conditions. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1) and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20) were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1) were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. Gene ontology analysis revealed enrichment of upregulated genes related to mesenchymal cell differentiation and signal transduction. Lithium priming led to enhanced collagen 1 synthesis and osteogenic induction of lithium pretreated MSCs resulted in enhanced expression of Runx2, ALP and bone sialoprotein. However, siRNA-mediated knockdown of RRAD, CLEC3B and ATF4 attenuated lithium-induced osteogenic priming, identifying a role for RRAD, a member of small GTP binding protein family, in osteoblast differentiation. In conclusion, our data highlight the transcriptome reprogramming potential of lithium resulting in higher propensity of lithium “primed” MSCs for osteoblastic differentiation. PMID:23383279

  7. Angiogenic CXC chemokine expression during differentiation of human mesenchymal stem cells towards the osteoblastic lineage.

    PubMed

    Bischoff, D S; Zhu, J H; Makhijani, N S; Kumar, A; Yamaguchi, D T

    2008-02-15

    The potential role of ELR(+) CXC chemokines in early events in bone repair was studied using human mesenchymal stem cells (hMSCs). Inflammation, which occurs in the initial phase of tissue healing in general, is critical to bone repair. Release of cytokines from infiltrating immune cells and injured bone can lead to recruitment of MSCs to the region of repair. CXC chemokines bearing the Glu-Leu-Arg (ELR) motif are also released by inflammatory cells and serve as angiogenic factors stimulating chemotaxis and proliferation of endothelial cells. hMSCs, induced to differentiate with osteogenic medium (OGM) containing ascorbate, beta-glycerophosphate (beta-GP), and dexamethasone (DEX), showed an increase in mRNA and protein secretion of the ELR(+) CXC chemokines CXCL8 and CXCL1. CXCL8 mRNA half-life studies reveal an increase in mRNA stability upon OGM stimulation. Increased expression and secretion is a result of DEX in OGM and is dose-dependent. Inhibition of the glucocorticoid receptor with mifepristone only partially inhibits DEX-stimulated CXCL8 expression indicating both glucocorticoid receptor dependent and independent pathways. Treatment with signal transduction inhibitors demonstrate that this expression is due to activation of the ERK and p38 mitogen-activated protein kinase (MAPK) pathways and is mediated through the G(alphai)-coupled receptors. Angiogenesis assays demonstrate that OGM-stimulated conditioned media containing secreted CXCL8 and CXCL1 can induce angiogenesis of human microvascular endothelial cells in an in vitro Matrigel assay. PMID:17583554

  8. On the probability of dinosaur fleas.

    PubMed

    Dittmar, Katharina; Zhu, Qiyun; Hastriter, Michael W; Whiting, Michael F

    2016-01-01

    Recently, a set of publications described flea fossils from Jurassic and Early Cretaceous geological strata in northeastern China, which were suggested to have parasitized feathered dinosaurs, pterosaurs, and early birds or mammals. In support of these fossils being fleas, a recent publication in BMC Evolutionary Biology described the extended abdomen of a female fossil specimen as due to blood feeding.We here comment on these findings, and conclude that the current interpretation of the evolutionary trajectory and ecology of these putative dinosaur fleas is based on appeal to probability, rather than evidence. Hence, their taxonomic positioning as fleas, or stem fleas, as well as their ecological classification as ectoparasites and blood feeders is not supported by currently available data. PMID:26754250

  9. 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)

  10. Songs the Dinosaurs Sang!.

    ERIC Educational Resources Information Center

    Greenwald, Nina L.

    1998-01-01

    Presents a lesson plan that uses a constructivist approach for developing and challenging students' different thinking strengths. In the context of musical and bodily-kinesthetic thinking, elementary school students interpret the sounds and movements the dinosaurs made as they negotiated their primitive environments. (CR)

  11. 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…

  12. Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold.

    PubMed

    Xin, Xuejun; Hussain, Mohammad; Mao, Jeremy J

    2007-01-01

    Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(d,l-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760+/-210 nm. The average Young's modulus of electrospun PLGA nanofibers was 42+/-26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1-4 weeks at a density of 2 x 10(6)cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells. PMID:17010425

  13. Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold

    PubMed Central

    Xin, Xuejun; Hussain, Mohammad; Mao, Jeremy J.

    2010-01-01

    Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(D,L-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760±210 nm. The average Young’s modulus of electrospun PLGA nanofibers was 42±26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1–4 weeks at a density of 2×106 cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells. PMID:17010425

  14. Adult Thymus Contains FoxN1− Epithelial Stem Cells that Are Bipotent for Medullary and Cortical Thymic Epithelial Lineages

    PubMed Central

    Ucar, Ahmet; Ucar, Olga; Klug, Paula; Matt, Sonja; Brunk, Fabian; Hofmann, Thomas G.; Kyewski, Bruno

    2014-01-01

    Summary Within the thymus, two major thymic epithelial cell (TEC) subsets—cortical and medullary TECs—provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed “thymospheres”). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness. PMID:25148026

  15. 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. PMID:26041865

  16. 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. PMID:16817695

  17. The first Brazilian Dinosaur Symposium

    NASA Astrophysics Data System (ADS)

    dos Anjos Candeiro, Carlos Roberto; da Silva Marinho, Thiago

    2015-08-01

    The 1st Brazilian Dinosaur Symposium gathered paleontologists, geologists, and paleoartists in the city of Ituiutaba, Minas Gerais State, Brazil, from April 21st to 24th, 2013. The Dinosaur Symposium in the Pontal Campus of the Universidade Federal de Uberlândia, Minas Gerais State, Brazil provided an opportunity to share many new results of dinosaur research being conducted around the world. The symposium coincided with a new dawn of scientific advances in dinosaur paleontology further expanding its importance, interest and credibility worldwide.

  18. 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; Lwer, Martin; Lehr, Hans-Anton; Kreft, Andreas; Eshkind, Leonid; Hildebrandt, Andreas; Abassi, Yasmin; Heck, Rosario; Dehof, Anna Katharina; Ohngemach, Svetlana; Sprengel, Rolf; Wrtge, 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

  19. 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. PMID:25371011

  20. 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

  1. 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

  2. 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. PMID:26624996

  3. 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 Central

    Lu, Chenggang; Fuller, Margaret T.

    2015-01-01

    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. PMID:26624996

  4. A dark day for dinosaurs

    NASA Astrophysics Data System (ADS)

    Edwards, Pete

    2015-11-01

    On average, 91 people are killed by asteroids each year. In her book Dark Matter and the Dinosaurs, theoretical physicist Lisa Randall focuses on a novel question: how did a dinosaur-killing asteroid end up on its collision course with Earth in the first place?

  5. 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…

  6. 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.…

  7. Origin of avian genome size and structure in non-avian dinosaurs.

    PubMed

    Organ, Chris L; Shedlock, Andrew M; Meade, Andrew; Pagel, Mark; Edwards, Scott V

    2007-03-01

    Avian genomes are small and streamlined compared with those of other amniotes by virtue of having fewer repetitive elements and less non-coding DNA. This condition has been suggested to represent a key adaptation for flight in birds, by reducing the metabolic costs associated with having large genome and cell sizes. However, the evolution of genome architecture in birds, or any other lineage, is difficult to study because genomic information is often absent for long-extinct relatives. Here we use a novel bayesian comparative method to show that bone-cell size correlates well with genome size in extant vertebrates, and hence use this relationship to estimate the genome sizes of 31 species of extinct dinosaur, including several species of extinct birds. Our results indicate that the small genomes typically associated with avian flight evolved in the saurischian dinosaur lineage between 230 and 250 million years ago, long before this lineage gave rise to the first birds. By comparison, ornithischian dinosaurs are inferred to have had much larger genomes, which were probably typical for ancestral Dinosauria. Using comparative genomic data, we estimate that genome-wide interspersed mobile elements, a class of repetitive DNA, comprised 5-12% of the total genome size in the saurischian dinosaur lineage, but was 7-19% of total genome size in ornithischian dinosaurs, suggesting that repetitive elements became less active in the saurischian lineage. These genomic characteristics should be added to the list of attributes previously considered avian but now thought to have arisen in non-avian dinosaurs, such as feathers, pulmonary innovations, and parental care and nesting. PMID:17344851

  8. Multi-Lineage Differentiation of Human Umbilical Cord Wharton’s Jelly Mesenchymal Stromal Cells Mediates Changes in the Expression Profile of Stemness Markers

    PubMed Central

    Ali, Hamad; Al-Yatama, Majda K.; Abu-Farha, Mohamed; Behbehani, Kazem; Al Madhoun, Ashraf

    2015-01-01

    Wharton’s Jelly- derived Mesenchymal stem cells (WJ-MSCs) have gained interest as an alternative source of stem cells for regenerative medicine because of their potential for self-renewal, differentiation and unique immunomodulatory properties. Although many studies have characterized various WJ-MSCs biologically, the expression profiles of the commonly used stemness markers have not yet been addressed. In this study, WJ-MSCs were isolated and characterized for stemness and surface markers expression. Flow cytometry, immunofluorescence and qRT-PCR analysis revealed predominant expression of CD29, CD44, CD73, CD90, CD105 and CD166 in WJ-MSCs, while the hematopoietic and endothelial markers were absent. Differential expression of CD 29, CD90, CD105 and CD166 following adipogenic, osteogenic and chondrogenic induction was observed. Furthermore, our results demonstrated a reduction in CD44 and CD73 expressions in response to the tri-lineage differentiation induction, suggesting that they can be used as reliable stemness markers, since their expression was associated with undifferentiated WJ-MSCs only. PMID:25848763

  9. A bizarre Cretaceous theropod dinosaur from Patagonia and the evolution of Gondwanan dromaeosaurids.

    PubMed

    Novas, Fernando E; Pol, Diego; Canale, Juan I; Porfiri, Juan D; Calvo, Jorge O

    2009-03-22

    Fossils of a predatory dinosaur provide novel information about the evolution of unenlagiines, a poorly known group of dromaeosaurid theropods from Gondwana. The new dinosaur is the largest dromaeosaurid yet discovered in the Southern Hemisphere and depicts bizarre cranial and postcranial features. Its long and low snout bears numerous, small-sized conical teeth, a condition resembling spinosaurid theropods. Its short forearms depart from the characteristically long-armed condition of all dromaeosaurids and their close avian relatives. The new discovery amplifies the range of morphological disparity among unenlagiines, demonstrating that by the end of the Cretaceous this clade included large, short-armed forms alongside crow-sized, long-armed, possibly flying representatives. The new dinosaur is the youngest record of dromaeosaurids from Gondwana and represents a previously unrecognized lineage of large predators in Late Cretaceous dinosaur faunas mainly dominated by abelisaurid theropods. PMID:19129109

  10. Regional and Stage-Specific Effects of Prospectively Purified Vascular Cells on the Adult V-SVZ Neural Stem Cell Lineage

    PubMed Central

    Crouch, Elizabeth E.; Liu, Chang; Silva-Vargas, Violeta

    2015-01-01

    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. PMID:25788671

  11. F-box protein FBXL16 binds PP2A-B55α and regulates differentiation of embryonic stem cells along the FLK1+ lineage.

    PubMed

    Honarpour, Narimon; Rose, Christopher M; Brumbaugh, Justin; Anderson, Jody; Graham, Robert L J; Sweredoski, Michael J; Hess, Sonja; Coon, Joshua J; Deshaies, Raymond J

    2014-03-01

    The programmed formation of specific tissues from embryonic stem cells is a major goal of regenerative medicine. To identify points of intervention in cardiac tissue formation, we performed an siRNA screen in murine embryonic stem cells to identify ubiquitin system genes that repress cardiovascular tissue formation. Our screen uncovered an F-box protein, Fbxl16, as a repressor of one of the earliest steps in the cardiogenic lineage: FLK1+ progenitor formation. Whereas F-box proteins typically form SCF ubiquitin ligases, shotgun mass spectrometry revealed that FBXL16 instead binds protein phosphatase 2A (PP2A) containing a B55 specificity subunit (PP2A(B55)). Phosphoproteomic analyses indicate that FBXL16 negatively regulates phosphorylation of the established PP2A(B55) substrate, vimentin. We suggest that FBXL16 negatively regulates the activity of B55α-PP2A to modulate the genesis of FLK1+ progenitor cells. PMID:24390425

  12. Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes

    PubMed Central

    Zambetti, Noemi A.; Bindels, Eric M. J.; Van Strien, Paulina M. H.; Valkhof, Marijke G.; Adisty, Maria N.; Hoogenboezem, Remco M.; Sanders, Mathijs A.; Rommens, Johanna M.; Touw, Ivo P.; Raaijmakers, Marc H. G. P.

    2015-01-01

    Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease is associated with loss-of-function mutations in the SBDS gene, implicated in ribosome biogenesis, but the cellular and molecular events driving cell specific phenotypes in ribosomopathies remain poorly defined. Here, we established what is to our knowledge the first mammalian model of neutropenia in Shwachman-Diamond syndrome through targeted downregulation of Sbds in hematopoietic stem and progenitor cells expressing the myeloid transcription factor CCAAT/enhancer binding protein α (Cebpa). Sbds deficiency in the myeloid lineage specifically affected myelocytes and their downstream progeny while, unexpectedly, it was well tolerated by rapidly cycling hematopoietic progenitor cells. Molecular insights provided by massive parallel sequencing supported cellular observations of impaired cell cycle exit and formation of secondary granules associated with the defect of myeloid lineage progression in myelocytes. Mechanistically, Sbds deficiency activated the p53 tumor suppressor pathway and induced apoptosis in these cells. Collectively, the data reveal a previously unanticipated, selective dependency of myelocytes and downstream progeny, but not rapidly cycling progenitors, on this ubiquitous ribosome biogenesis protein, thus providing a cellular basis for the understanding of myeloid lineage biased defects in Shwachman-Diamond syndrome. PMID:26185170

  13. A misexpression screen reveals effects of bag-of-marbles and TGF beta class signaling on the Drosophila male germ-line stem cell lineage.

    PubMed Central

    Schulz, Cordula; Kiger, Amy A; Tazuke, Salli I; Yamashita, Yukiko M; Pantalena-Filho, Luiz C; Jones, D Leanne; Wood, Cricket G; Fuller, Margaret T

    2004-01-01

    Male gametes are produced throughout reproductive life by a classic stem cell mechanism. However, little is known about the molecular mechanisms for lineage production that maintain male germ-line stem cell (GSC) populations, regulate mitotic amplification divisions, and ensure germ cell differentiation. Here we utilize the Drosophila system to identify genes that cause defects in the male GSC lineage when forcibly expressed. We conducted a gain-of-function screen using a collection of 2050 EP lines and found 55 EP lines that caused defects at early stages of spermatogenesis upon forced expression either in germ cells or in surrounding somatic support cells. Most strikingly, our analysis of forced expression indicated that repression of bag-of-marbles (bam) expression in male GSC is important for male GSC survival, while activity of the TGF beta signal transduction pathway may play a permissive role in maintenance of GSCs in Drosophila testes. In addition, forced activation of the TGF beta signal transduction pathway in germ cells inhibits the transition from the spermatogonial mitotic amplification program to spermatocyte differentiation. PMID:15238523

  14. Differentiation of retinal ganglion cells and photoreceptor precursors from mouse induced pluripotent stem cells carrying an Atoh7/Math5 lineage reporter.

    PubMed

    Xie, Bin-Bin; Zhang, Xiang-Mei; Hashimoto, Takao; Tien, Amy H; Chen, Andrew; Ge, Jian; Yang, Xian-Jie

    2014-01-01

    The neural retina is a critical component of the visual system, which provides the majority of sensory input in humans. Various retinal degenerative diseases can result in the permanent loss of retinal neurons, especially the light-sensing photoreceptors and the centrally projecting retinal ganglion cells (RGCs). The replenishment of lost RGCs and the repair of optic nerve damage are particularly challenging, as both RGC specification and their subsequent axonal growth and projection involve complex and precise regulation. To explore the developmental potential of pluripotent stem cell-derived neural progenitors, we have established mouse iPS cells that allow cell lineage tracing of progenitors that have expressed Atoh7/Math5, a bHLH transcription factor required for RGC production. These Atoh7 lineage reporter iPS cells encode Cre to replace one copy of the endogenous Atoh7 gene and a Cre-dependent YFP reporter in the ROSA locus. In addition, they express pluripotent markers and are capable of generating teratomas in vivo. Under anterior neural induction and neurogenic conditions in vitro, the Atoh7-Cre/ROSA-YFP iPS cells differentiate into neurons that co-express various RGC markers and YFP, indicating that these neurons are derived from Atoh7-expressing progenitors. Consistent with previous in vivo cell lineage studies, the Atoh7-Cre/ROSA-YFP iPS cells also give rise to a subset of Crx-positive photoreceptor precursors. Furthermore, inhibition of Notch signaling in the iPSC cultures results in a significant increase of YFP-positive RGCs and photoreceptor precursors. Together, these results show that Atoh7-Cre/ROSA-YFP iPS cells can be used to monitor the development and survival of RGCs and photoreceptors from pluripotent stem cells. PMID:25401462

  15. Creationism and the Dinosaur Boom.

    ERIC Educational Resources Information Center

    Stokes, William Lee

    1989-01-01

    Discusses books and materials published by creationist organizations to promote creation-science interpretations on the demise of the dinosaur. Compares many creationist theories with current evolution theories and geological records. (MVL)

  16. Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16.

    PubMed

    Ueda, Koki; Yoshimi, Akihide; Kagoya, Yuki; Nishikawa, Satoshi; Marquez, Victor E; Nakagawa, Masahiro; Kurokawa, Mineo

    2014-05-01

    Leukemia stem cells (LSC) are resistant to conventional chemotherapy and persistent LSC after chemotherapy are supposed to be a major cause of relapse. However, information on genetic or epigenetic regulation of stem cell properties is still limited and LSC-targeted drugs have scarcely been identified. Epigenetic regulators are associated with many cellular processes including maintenance of stem cells. Of note are polycomb group proteins, because they potentially control stemness, and can be pharmacologically targeted by a selective inhibitor (DZNep). Therefore, we investigated the therapeutic potential of EZH2 inhibition in mixed lineage leukemia (MLL) fusion leukemia. Intriguingly, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced leukemia initiating cells (LIC) frequency. Expression analysis suggested that p16 upregulation was responsible for LICs reduction. Knockdown of p16 canceled the survival advantage of mice treated with DZNep. Chromatin immunoprecipitation assays demonstrated that EZH2 was highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL and Hoxa9/Meis1 transduced cells but not in E2A/HLF transduced cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells. In summary, our findings show that EZH2 is a potential therapeutic target of MLL fusion leukemia stem cells. PMID:24612037

  17. A Transposon-Mediated System for Flexible Control of Transgene Expression in Stem and Progenitor-Derived Lineages

    PubMed Central

    Akhtar, Aslam Abbasi; Molina, Jessica; Dutra-Clarke, Marina; Kim, Gi Bum; Levy, Rachelle; Schreiber-Stainthorp, William; Danielpour, Moise; Breunig, Joshua J.

    2015-01-01

    Summary Precise methods for transgene regulation are important to study signaling pathways and cell lineages in biological systems where gene function is often recycled within and across lineages. We engineered a genetic toolset for flexible transgene regulation in these diverse cellular contexts. Specifically, we created an optimized piggyBac transposon-based system, allowing for the facile generation of stably transduced cell lineages in vivo and in vitro. The system, termed pB-Tet-GOI (piggyBac-transposable tetracycline transactivator-mediated flexible expression of a genetic element of interest), incorporates the latest generation of tetracycline (Tet) transactivator and reverse Tet transactivator variants—along with engineered mutants—in order to provide regulated transgene expression upon addition or removal of doxycycline (dox). Altogether, the flexibility of the system allows for dox-induced, dox-suppressed, dox-resistant (i.e., constitutive), and dox-induced/constitutive regulation of transgenes. This versatile strategy provides reversible temporal regulation of transgenes with robust inducibility and minimal leakiness. PMID:25702640

  18. Universal hydraulics of the flowering plants: vessel diameter scales with stem length across angiosperm lineages, habits and climates.

    PubMed

    Olson, Mark E; Anfodillo, Tommaso; Rosell, Julieta A; Petit, Giai; Crivellaro, Alan; Isnard, Sandrine; León-Gómez, Calixto; Alvarado-Cárdenas, Leonardo O; Castorena, Matiss

    2014-08-01

    Angiosperm hydraulic performance is crucially affected by the diameters of vessels, the water conducting conduits in the wood. Hydraulic optimality models suggest that vessels should widen predictably from stem tip to base, buffering hydrodynamic resistance accruing as stems, and therefore conductive path, increase in length. Data from 257 species (609 samples) show that vessels widen as predicted with distance from the stem apex across angiosperm orders, habits and habitats. Standardising for stem length, vessels are only slightly wider in warm/moist climates and in lianas, showing that, rather than climate or habit, plant size is by far the main driver of global variation in mean vessel diameter. Terminal twig vessels become wider as plant height increases, while vessel density decreases slightly less than expected tip to base. These patterns lead to testable predictions regarding evolutionary strategies allowing plants to minimise carbon costs per unit leaf area even as height increases. PMID:24847972

  19. Differentiation of Human Umbilical Cord Matrix Mesenchymal Stem Cells into Neural-Like Progenitor Cells and Maturation into an Oligodendroglial-Like Lineage

    PubMed Central

    Leite, Cristiana; Silva, N. Tatiana; Mendes, Sandrine; Ribeiro, Andreia; de Faria, Joana Paes; Loureno, Tnia; dos Santos, Francisco; Andrade, Pedro Z.; Cardoso, Carla M. P.; Vieira, Margarida; Paiva, Artur; da Silva, Cludia L.; Cabral, Joaquim M. S.; Relvas, Joo B.; Gros, Mrio

    2014-01-01

    Mesenchymal stem cells (MSCs) are viewed as safe, readily available and promising adult stem cells, which are currently used in several clinical trials. Additionally, their soluble-factor secretion and multi-lineage differentiation capacities place MSCs in the forefront of stem cell types with expected near-future clinical applications. In the present work MSCs were isolated from the umbilical cord matrix (Wharton's jelly) of human umbilical cord samples. The cells were thoroughly characterized and confirmed as bona-fide MSCs, presenting in vitro low generation time, high proliferative and colony-forming unit-fibroblast (CFU-F) capacity, typical MSC immunophenotype and osteogenic, chondrogenic and adipogenic differentiation capacity. The cells were additionally subjected to an oligodendroglial-oriented step-wise differentiation protocol in order to test their neural- and oligodendroglial-like differentiation capacity. The results confirmed the neural-like plasticity of MSCs, and suggested that the cells presented an oligodendroglial-like phenotype throughout the differentiation protocol, in several aspects sharing characteristics common to those of bona-fide oligodendrocyte precursor cells and differentiated oligodendrocytes. PMID:25357129

  20. c-Maf regulates pluripotency genes, proliferation/self-renewal, and lineage commitment in ROS-mediated senescence of human mesenchymal stem cells

    PubMed Central

    Li, Nan-Ting; Wu, Yao-Ming; Lin, Ming-Tsan; Hung, Shih-Chieh; Yen, Men-Luh

    2015-01-01

    Mesenchymal stem cells (MSCs) are therapeutically relevant multilineage and immunomodulatory progenitors. Ex vivo expansion of these rare cells is necessary for clinical application and can result in detrimental senescent effects, with mechanisms still largely unknown. We found that vigorous ex vivo expansion of human adipose tissue-derived MSCs (hAMSCs) results in proliferative decline, cell cycle arrest, and altered differentiation capacity. This senescent phenotype was associated with reactive oxygen species (ROS) accumulation, and with increased expression of G1 cell -cycle inhibitors— p15INK4b and p16INK4a — but decreased expression of pluripotency genes—Oct-4, Sox-2, Nanog, and c-Myc—as well as c-Maf a co-factor of MSC lineage-specific transcription factor and sensitive to oxidative stress. These global changes in the transcriptional and functional programs of proliferation, differentiation, and self-renewal were all mediated by ROS-induced suppression of c-Maf, as evidenced by binding of c-Maf to promoter regions of multiple relevant genes in hAMSCs which could be reduced by exogenous ROS. Our findings implicate the strong effects of ROS on multiple stem cell functions with a central role for c-Maf in stem cell senescence. PMID:26496036

  1. 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. PMID:25065505

  2. Regulation of survival in adult hippocampal and glioblastoma stem cell lineages by the homeodomain-only protein HOP

    PubMed Central

    De Toni, Arianna; Zbinden, Marie; Epstein, Jonathan A; Altaba, Ariel Ruiz i; Prochiantz, Alain; Caillé, Isabelle

    2008-01-01

    Background Homeodomain proteins play critical roles in shaping the development of the embryonic central nervous system in mammals. After birth, neurogenic activities are relegated to stem cell niches, which include the subgranular layer of the dentate gyrus of the hippocampus. Here, we have analyzed the function of HOP (Homeodomain only protein) in this stem cell niche and in human glioblastomas. Results We find that HOP is strongly expressed by radial astrocytes of the dentate gyrus in mice, which are stem cells that give rise to hippocampal granular neurons throughout adulthood. Deletion or down-regulation of HOP results in a decrease of apoptosis of these stem cells without changes in proliferation, and in an increase in the number of newly formed granule neurons. We also find that human glioblastomas largely lack HOP expression and that reintroduction of HOP function in glioma cells cultured as gliomaspheres leads to enhanced apoptosis in a subset of cases. In these cells, HOP function decreases clonogenicity. Conclusion These data suggest that HOP participates in the regulation of the adult mouse hippocampal stem cell niche by negatively affecting cell survival. In addition, HOP may work as a tumor suppressor in a subset of glioblastomas. HOP function thus appears to be critical in the adult brain in a region of continued plasticity, and its deregulation may contribute to disease. PMID:18507846

  3. Effects of CoCl2 on multi-lineage differentiation of C3H/10T1/2 mesenchymal stem cells

    PubMed Central

    Yoo, Hong Il; Moon, Yeon Hee

    2016-01-01

    Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride (CoCl2) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of CoCl2 preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. CoCl2 treatment of MSCs markedly increased HIF-1α and VEGF mRNA, and protein expression of HIF-1α. Temporary preconditioning of MSCs with CoCl2 induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. CoCl2 also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. CoCl2 suppressed the expression of adipogenic markers including PPARγ, aP2, and C/EBPα, and inhibited adipogenesis. Temporary preconditioning with CoCl2 could affect the multi-lineage differentiation of MSCs. PMID:26807023

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

    SciTech Connect

    Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin; Chung, Chong-Pyoung; Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul ; Park, Yoon Jeong

    2012-03-09

    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. 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 {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 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.

  5. 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

  6. 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. PMID:26023131

  7. 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,…

  8. 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…

  9. 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,

  10. Rat malignant fibrous histiocytoma (MFH)-derived cloned cell lines (MT-8 and MT-9) show different differentiation in mesenchymal stem cell lineage.

    PubMed

    Kotera, Takashi; Katou-Ichikawa, Chisa; Tennakoon, Anusha Hemamali; Tanaka, Miyuu; Tanaka, Natsuki; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-10-01

    Malignant fibrous histiocytomas (MFHs) show a storiform growth pattern consisting of fibroblastic, histiocytic and undifferentiated mesenchymal cells with possible multipotency. Because MFH-like tumors are induced experimentally by some chemicals and materials, it is important to know the histogenesis of MFHs. We analyzed in vitro and in vivo characteristics of two cloned cell lines (MT-8 and MT-9) established from a spontaneous MFH found in an aged F344 rat. MT-8 and MT-9 cultured cells and their tumors induced in syngeneic rats by injection were investigated morphologically, and their tumors were evaluated by immunohistochemistry. Gene expression profiles of their cultures and induced tumors were analyzed by the comprehensive gene analysis. MT-8 cells had less developed organelles and the induced tumors represented histological characteristics of undifferentiated sarcoma (sarcoma not otherwise specified (NOS)), whereas MT-9 cells had relatively well-developed intracytoplasmic organelles such as endoplasmic reticulum, mitochondria and lysosomes and the tumors showed a storiform growth pattern typical of MFHs. MT-8 and MT-9 tumors were immuno-positive for vimentin, and the reactivity for stem cell markers (nestin, CD90, CD34, and A3) appeared to be greater in MT-9 tumor cells, and their tumor cells did not react to markers for well-differentiated cells of epithelial, myogenic and neurogenic tissues except for faint reaction for S-100 protein in MT-9 tumors. The gene analyses revealed that genes relating to "cell differentiation" were more activated in MT-9 than MT-8 tumors, whereas those involved in "cell cycle" were greater in MT-8 than MT-9 tumors. In MT-8 and MT-9, additionally, genes involved in "cell differentiation" were much greater in their tumors than in their cultures. These findings indicate that MT-8 cells are poorly differentiated mesenchymal stem cells which induce sarcomas NOS, whereas MT-9 cells, which can develop typical MFHs, have more differentiated stem cell nature with greater multipotential differentiation. In MFHs, collectively, MT-8 and MT-9 cells are regarded as "tumor stem cells" and "tumor precursors" in the stem cell lineage, respectively, according to the concept of "cancer stem cell theory". PMID:26208870

  11. Alginate Microcapsule as a 3D Platform for Propagation and Differentiation of Human Embryonic Stem Cells (hESC) to Different Lineages

    PubMed Central

    Sidhu, Kuldip; Kim, Jaemin; Chayosumrit, Methichit; Dean, Sophia; Sachdev, Perminder

    2012-01-01

    Human embryonic stem cells (hESC) are emerging as an attractive alternative source for cell replacement therapy since they can be expanded in culture indefinitely and differentiated to any cell types in the body. Various types of biomaterials have also been used in stem cell cultures to provide a microenvironment mimicking the stem cell niche1-3. The latter is important for promoting cell-to-cell interaction, cell proliferation, and differentiation into specific lineages as well as tissue organization by providing a three-dimensional (3D) environment4 such as encapsulation. The principle of cell encapsulation involves entrapment of living cells within the confines of semi-permeable membranes in 3D cultures2. These membranes allow for the exchange of nutrients, oxygen and stimuli across the membranes, whereas antibodies and immune cells from the host that are larger than the capsule pore size are excluded5. Here, we present an approach to culture and differentiate hESC DA neurons in a 3D microenvironment using alginate microcapsules. We have modified the culture conditions2 to enhance the viability of encapsulated hESC. We have previously shown that the addition of p160-Rho-associated coiled-coil kinase (ROCK) inhibitor, Y-27632 and human fetal fibroblast-conditioned serum replacement medium (hFF-CM) to the 3D platform significantly enhanced the viability of encapsulated hESC in which the cells expressed definitive endoderm marker genes1. We have now used this 3D platform for the propagation of hESC and efficient differentiation to DA neurons. Protein and gene expression analyses after the final stage of DA neuronal differentiation showed an increased expression of tyrosine hydroxylase (TH), a marker for DA neurons, >100 folds after 2 weeks. We hypothesized that our 3D platform using alginate microcapsules may be useful to study the proliferation and directed differentiation of hESC to various lineages. This 3D system also allows the separation of feeder cells from hESC during the process of differentiation and also has potential for immune-isolation during transplantation in the future. PMID:22433991

  12. 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 optimizing culture conditions to generate other specific lineage-oriented hiPSCs, allowing for a very simple differentiation. PMID:25875613

  13. First dinosaurs from Saudi Arabia.

    PubMed

    Kear, Benjamin P; Rich, Thomas H; Vickers-Rich, Patricia; Ali, Mohammed A; Al-Mufarreh, Yahya A; Matari, Adel H; Al-Massari, Abdu M; Nasser, Abdulaziz H; Attia, Yousry; Halawani, Mohammed A

    2013-01-01

    Dinosaur remains from the Arabian subcontinent are exceedingly rare, and those that have been documented manifest indeterminate affinities. Consequently the discovery of a small, but diagnostic, accumulation of elements from Campanian-Maastrichtian (~ 75 Ma) deposits in northwestern Saudi Arabia is significant because it constitutes the first taxonomically identifiable dinosaur material described from the Arabian Peninsula. The fossils include a series of possible lithostrotian titanosaur caudal vertebrae, and some isolated theropod marginal teeth that share unique character states and metric parameters (analyzed using multivariate statistical methods) with derived abelisaurids - this is the first justifiable example of a non-avian carnivorous dinosaur clade from Arabia. The recognition of titanosaurians and abelisaurids from Saudi Arabia extends the palaeogeographical range of these groups along the entire northern Gondwanan margin during the latest Cretaceous. Moreover, given the extreme paucity of coeval occurrences elsewhere, the Saudi Arabian fossils provide a tantalizing glimpse into dinosaurian assemblage diversity within the region. PMID:24386326

  14. First Dinosaurs from Saudi Arabia

    PubMed Central

    Kear, Benjamin P.; Rich, Thomas H.; Vickers-Rich, Patricia; Ali, Mohammed A.; Al-Mufarreh, Yahya A.; Matari, Adel H.; Al-Massari, Abdu M.; Nasser, Abdulaziz H.; Halawani, Mohammed A.

    2013-01-01

    Dinosaur remains from the Arabian subcontinent are exceedingly rare, and those that have been documented manifest indeterminate affinities. Consequently the discovery of a small, but diagnostic, accumulation of elements from Campanian-Maastrichtian (∼75 Ma) deposits in northwestern Saudi Arabia is significant because it constitutes the first taxonomically identifiable dinosaur material described from the Arabian Peninsula. The fossils include a series of possible lithostrotian titanosaur caudal vertebrae, and some isolated theropod marginal teeth that share unique character states and metric parameters (analyzed using multivariate statistical methods) with derived abelisaurids – this is the first justifiable example of a non-avian carnivorous dinosaur clade from Arabia. The recognition of titanosaurians and abelisaurids from Saudi Arabia extends the palaeogeographical range of these groups along the entire northern Gondwanan margin during the latest Cretaceous. Moreover, given the extreme paucity of coeval occurrences elsewhere, the Saudi Arabian fossils provide a tantalizing glimpse into dinosaurian assemblage diversity within the region. PMID:24386326

  15. 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 herbivores in terms of relative abundance. Sympatric hadrosaurids may have avoided competing with one another by feeding differentially using bipedal and quadrupedal postures. These ecological relationships evidently proved to be evolutionarily stable because they characterize the herbivore assemblage of the Dinosaur Park Formation through time. If niche partitioning served to facilitate the rich diversity of these animals, it may have been achieved by other means in addition to feeding height stratification. Consideration of other feeding height proxies, including dental microwear and skull morphology, may help to alleviate problems of underdetermination identified here. PMID:23557203

  16. The earliest known sauropod dinosaur.

    PubMed

    Buffetaut, E; Suteethorn, V; Cuny, G; Tong, H; Le Loeuff, J; Khansubha, S; Jongautchariyakul, S

    2000-09-01

    Sauropods were a very successful group of dinosaurs during the Jurassic and Cretaceous periods, but their earlier history is poorly known. Until now, the earliest reported sauropod bones were from the Early Jurassic, and the only tentative evidence of earlier sauropods was in the form of controversial footprints. Here we report the discovery of an incomplete sauropod skeleton from the Late Triassic period of Thailand, which provides the first osteological evidence of pre-Jurassic sauropods. This dinosaur is markedly different from prosauropods and substantiates theoretical predictions that there was a fairly long period of sauropod evolution during the Triassic. PMID:10993074

  17. Transcriptome profiling and sequencing of differentiated human hematopoietic stem cells reveal lineage-specific expression and alternative splicing of genes

    PubMed Central

    Liu, Poching; Barb, Jennifer; Woodhouse, Kimberly; Taylor, James G.; Munson, Peter J.

    2011-01-01

    Hematopoietic differentiation is strictly regulated by complex network of transcription factors that are controlled by ligands binding to cell surface receptors. Disruptions of the intricate sequences of transcriptional activation and suppression of multiple genes cause hematological diseases, such as leukemias, myelodysplastic syndromes, or myeloproliferative syndromes. From a clinical standpoint, deciphering the pattern of gene expression during hematopoiesis may help unravel disease-specific mechanisms in hematopoietic malignancies. Herein, we describe a human in vitro hematopoietic model system where lineage-specific differentiation of CD34+ cells was accomplished using specific cytokines. Microarray and RNAseq-based whole transcriptome and exome analysis was performed on the differentiated erythropoietic, granulopoietic, and megakaryopoietic cells to delineate changes in expression of whole transcripts and exons. Analysis on the Human 1.0 ST exon arrays indicated differential expression of 172 genes (P < 0.0000001) and significant alternate splicing of 86 genes during differentiation. Pathway analysis identified these genes to be involved in Rac/RhoA signaling, Wnt/B-catenin signaling and alanine/aspartate metabolism. Comparison of the microarray data to next generation RNAseq analysis during erythroid differentiation demonstrated a high degree of correlation in gene (R = 0.72) and exon (R = 0.62) expression. Our data provide a molecular portrait of events that regulate differentiation of hematopoietic cells. Knowledge of molecular processes by which the cells acquire their cell-specific fate would be beneficial in developing cell-based therapies for human diseases. PMID:21828245

  18. Micro-/nano- sized hydroxyapatite directs differentiation of rat bone marrow derived mesenchymal stem cells towards an osteoblast lineage.

    PubMed

    Huang, Yan; Zhou, Gang; Zheng, Lisha; Liu, Haifeng; Niu, Xufeng; Fan, Yubo

    2012-04-01

    Regenerative medicine consisting of cells and materials provides a new way for the repair and regeneration of tissues and organs. Nano-biomaterials are highlighted due to their advantageous features compared with conventional micro-materials. The aim of this study is to investigate the effects of micro-/nano- sized hydroxyapatite (μ/n-HA) on the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). μ/n-HA were prepared by a microwave synthesizer and precipitation method, respectively. Different sizes of μ/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It was shown that rBMSCs expressed higher levels of osteoblast-related markers by n-HA than μ-HA stimulation. The size of HA is an important factor for affecting the osteogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells. PMID:22371072

  19. Decellularized Liver Extracellular Matrix as Promising Tools for Transplantable Bioengineered Liver Promotes Hepatic Lineage Commitments of Induced Pluripotent Stem Cells.

    PubMed

    Park, Kyung-Mee; Hussein, Kamal Hany; Hong, Seok-Ho; Ahn, Cheol; Yang, Se-Ran; Park, Sung-Min; Kweon, Oh-Kyeong; Kim, Byeong-Moo; Woo, Heung-Myong

    2016-03-01

    Liver transplantation is the last resort for liver failure patients. However, due to the shortage of donor organs, bioengineered liver generated from decellularized whole liver scaffolds and induced pluripotent stem cell (iPSC)-derived hepatocytes (iPSC-Heps) is being studied as an alternative approach to treat liver disease. Nevertheless, there has been no report on both the interaction of iPSC-Heps with a liver extracellular matrix (ECM) and the analysis of recellularized iPSC-Heps into the whole liver scaffolds. In this study, we produced porcine iPSC-Heps, which strongly expressed the hepatic markers α-fetoprotein and albumin and exhibited hepatic functionalities, including glycogen storage, lipid accumulation, low-density lipoprotein uptake, and indocyanine green metabolism. Supplementation of ECM from porcine decellularized liver containing liver-derived growth factors stimulated the albumin expression of porcine iPSC-Heps during differentiation procedures. The iPSC-Heps were reseeded into decellularized liver scaffolds, and the recellularized liver was cultured using a continuous perfusion system. The recellularized liver scaffolds were transplanted into rats for a short term, and the grafts expressed hepatocyte markers and did not rupture. These results provide a foundation for development of bioengineered liver using stem cell and decellularized scaffolds. PMID:26801816

  20. Micro-/Nano- sized hydroxyapatite directs differentiation of rat bone marrow derived mesenchymal stem cells towards an osteoblast lineage

    NASA Astrophysics Data System (ADS)

    Huang, Yan; Zhou, Gang; Zheng, Lisha; Liu, Haifeng; Niu, Xufeng; Fan, Yubo

    2012-03-01

    Regenerative medicine consisting of cells and materials provides a new way for the repair and regeneration of tissues and organs. Nano-biomaterials are highlighted due to their advantageous features compared with conventional micro-materials. The aim of this study is to investigate the effects of micro-/nano- sized hydroxyapatite (μ/n-HA) on the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). μ/n-HA were prepared by a microwave synthesizer and precipitation method, respectively. Different sizes of μ/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It was shown that rBMSCs expressed higher levels of osteoblast-related markers by n-HA than μ-HA stimulation. The size of HA is an important factor for affecting the osteogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells.

  1. Support Your Local Dinosaur! -- A Survey of Dinosaur Teaching Resources.

    ERIC Educational Resources Information Center

    Barker, John A.

    1983-01-01

    Describes resources for teaching about dinosaurs. These include audiovisual aids (models, posters, jigsaw puzzles, filmstrips, 35mm slides, resource pack, worksheets, templates, tracing sheets, and films/video materials), books (for young and older students), and exhibits. Includes sources for all materials described. (JN)

  2. Explorationists and dinosaurs

    SciTech Connect

    French, W.S. )

    1993-02-01

    The exploration industry is changing, exploration technology is changing and the explorationist's job is changing. Resource companies are diversifying internationally and their central organizations are providing advisors rather than services. As a result, the relationship between the resource company and the contractor is changing. Resource companies are promoting standards so that all contract services in all parts of the world will look the same to their advisors. Contractors, for competitive reasons, want to look [open quotes]different[close quotes] from other contractors. The resource companies must encourage competition between contractors to insure the availability of new technology but must also resist the current trend of burdening the contractor with more and more of the risk involved in exploration. It is becoming more and more obvious that geophysical expenditures represent the best [open quotes]value added[close quotes] expenditures in exploration and development budgets. As a result, seismic-related contractors represent the growth component of our industry. The predominant growth is in 3-D seismic technology, and this growth is being further propelled by the computational power of the new generation of massively parallel computers and by recent advances in computer graphic techniques. Interpretation of seismic data involves the analysis of wavelet shapes and amplitudes prior to stacking the data. Thus, modern interpretation involves understanding compressional waves, shear waves, and propagating modes which create noise and interference. Modern interpretation and processing are carried out simultaneously, iteratively, and interactively and involve many physics-related concepts. These concepts are not merely tools for the interpretation, they are the interpretation. Explorationists who do not recognize this fact are going the way of the dinosaurs.

  3. Adipose-derived stem cell adhesion on laminin-coated microcarriers improves commitment toward the cardiomyogenic lineage.

    PubMed

    Karam, Jean-Pierre; Bonafè, Francesca; Sindji, Laurence; Muscari, Claudio; Montero-Menei, Claudia N

    2015-05-01

    For tissue-engineering studies of the infarcted heart it is essential to identify a source of cells that may provide cardiomyocyte progenitors, which is easy to amplify, accessible in adults, and allowing autologous grafts. Preclinical studies have shown that human adipose-derived stem cells (ADSCs) can differentiate into cardiomyocyte-like cells and improve heart function in myocardial infarction. We have developed pharmacologically active microcarriers (PAMs) which are biodegradable and biocompatible polymeric microspheres conveying cells on their biomimetic surface, therefore providing an adequate three-dimensional (3D) microenvironment. Moreover, they can release a growth factor in a prolonged manner. In order to implement ADSCs and PAMs for cardiac tissue engineering we first defined the biomimetic surface by studying the influence of matrix molecules laminin (LM) and fibronectin (FN), in combination with growth factors present in the cardiogenic niche, to further enhance the in vitro cardiac differentiation of ADSCs. We demonstrated that LM increased the expression of cardiac markers (Nkx2.5, GATA4, MEF2C) by ADSCs after 2 weeks in vitro. Interestingly, our results suggest that the 3D support provided by PAMs with a LM biomimetic surface (LM-PAMs) further enhanced the expression of cardiac markers and induced the expression of a more mature contractile protein, cardiac troponin I, compared with the 2D differentiating conditions after only 1 week in culture. The enrichment of the growth-factor cocktail with TGF-β1 potentiated the cardiomyogenic differentiation. These results suggest that PAMs offering a LM biomimetic surface may be efficiently used for applications combining adult stem cells in tissue-engineering strategies of the ischemic heart. PMID:25098676

  4. Immunoliposome-mediated delivery of neomycin phosphotransferase for the lineage-specific selection of differentiated/committed stem cell progenies: potential advantages over transfection with marker genes, fluorescence-activated and magnetic affinity cell-sorting.

    PubMed

    Heng, Boon Chin; Cao, Tong

    2005-01-01

    A major challenge in the therapeutic application of stem cells in regenerative medicine is the lineage-specific selection of their committed/differentiated progenies for transplantation. This is necessary to avoid engraftment of undesired lineages at the transplantation site, i.e. fibroblastic scar tissue, as well as to enhance the efficacy of transplantation therapy. Commonly used techniques for lineage-specific selection of committed/differentiated stem cell progenies include marker gene transfection, fluorescence-activated (FACS) and magnetic-affinity (MACS) cell-sorting. Nevertheless, these have their disadvantages for therapeutic applications. Marker gene transfection invariably leads to permanent genetic modification of stem cells, which in turn limits their use in human clinical therapy due to overwhelming ethical and safety concerns. FACS requires expensive instrumentation and highly-skilled personnel, and is unsuited for handling bulk quantities of cells that would almost certainly be required for transplantation therapy. MACS is a cheaper alternative, but the level of purity attained is also reduced. A possible novel approach that has yet to be investigated is immunoliposome-mediated delivery of neomycin phosphotranferase (NPT) for lineage-specific selection of stem cell progenies. This would avoid permanent genetic modification to the cell, unlike recombinant NPT expression linked to activation of specific promoter sequences. Moreover, it could potentially provide a much more practical and cost-effective alternative for handling bulk quantities of cells that would be required for transplantation therapy, as compared to FACS or MACS. As such, this alternative approach needs to be rigorously investigated, in view of its potentially useful applications in stem cell therapeutics. PMID:15922109

  5. Evolution: convergence in dinosaur crests.

    PubMed

    Hone, David W E

    2015-06-15

    The horned, ceratopsid dinosaurs can be easily split into two major groups based on their cranial structures, but now a new discovery shows that at least one genus 'switched sides' and convergently evolved the form of the other clade. PMID:26079078

  6. Fossil quality and naming dinosaurs.

    PubMed

    Benton, Michael J

    2008-12-23

    The intense interest in dinosaurs through the past 30 years might have led to an increase in poor practice in naming new species. A review of the data shows that the reverse is the case. For 130 years, from the 1820s to the 1950s, most new species of dinosaurs were based on scrappy and incomplete material. After 1960, the majority of new species have been based on complete skulls or skeletons, and sometimes on materials from several individuals. This switch in the quality of type specimens corresponds to the recent explosive renaissance of interest in dinosaurs, during which the number of new species named per year has risen, from three or four in the 1950s, to thirty or more today. The pattern of specimen quality varies by continent, with the highest proportion of new species based on good material in North America, then Asia, then South America, then Africa and finally Europe. This ranking reflects a complex pattern of perhaps overstudy in Europe, immensely rich reserves of new dinosaur materials in North America and Asia, and a relative paucity in South America and Africa. PMID:18796391

  7. The End of the Dinosaurs

    NASA Astrophysics Data System (ADS)

    Frankel, Charles

    1999-10-01

    The discovery of the giant Chicxulub impact crater, buried off the coast of Mexico, unveiled the solution to one of Earth's greatest mysteries--what killed the dinosaurs. Scientists uncovered physical evidence to explain the mass extinction that rocked the Earth 65 million years ago. Step-by-step, The End of the Dinosaurs: Chicxulub Crater and Mass Extinctions tells this great scientific detective story. Charles Frankel recounts the birth of the cosmic hypothesis, which holds that the crash of a meteor on the Earth's surface killed two-thirds of life and all the dinosaurs. He first provides a dramatic account of the impact and its aftermath. Frankel then goes on to detail the controversy that preceded the acceptance of the cosmic hypothesis, the search for the crater, its discovery and ongoing exploration, and the effect of the giant impact on the biosphere. In addition, he reviews other mass extinctions in the fossil record and the threat of asteroids and comets to our planet today. More than 70 photographs and diagrams enhance and help illustrate the material. Filled with drama and interesting science, The End of the Dinosaurs will readily appeal to both the general reader fascinated with the subject and the specialist always searching for more clues to this great mystery. Charles Frankel has written a number of articles on the earth sciences in books and magazines. His many books include Volcanoes of the Solar System (Cambridge University Press 1996).

  8. 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.

  9. A New Day for Dinosaurs.

    ERIC Educational Resources Information Center

    Kritsky, Gene

    1987-01-01

    Presents a series of activities that use dinosaurs as a theme for teaching biological and geological concepts. The activities can be adapted for use with middle school through college level biology students. Exercises address such topics as: evolutionary relationships of vertebrates; Mesozoic ecology; animal tracks; and mineral replacement…

  10. Estimating the diversity of dinosaurs

    PubMed Central

    Wang, Steve C.; Dodson, Peter

    2006-01-01

    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. PMID:16954187

  11. Temozolomide sensitizes stem-like cells of glioma spheres to TRAIL-induced apoptosis via upregulation of casitas B-lineage lymphoma (c-Cbl) protein.

    PubMed

    Zhitao, Jing; Long, Li; Jia, Liu; Yunchao, Ban; Anhua, Wu

    2015-12-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has potent antitumor effects in glioma cell lines but has shown little clinical benefit for patients. We investigated whether the widely used chemotherapeutic agent temozolomide (TMZ) can sensitize glioma stem-like cells (GSCs) from human glioblastoma multiforme (GBM) to TRAIL-induced apoptosis. GSCs were isolated from GBM, and stem cell properties were confirmed by immunocytochemistry and in vivo tumorigenicity. Primary GSCs (PGCs) were produced by serum treatment of GBM-derived cells. Changes in expression levels of various TRAIL-related signaling factors before and after TRAIL or TRAIL + TMZ treatment were measured by Western blotting. Overexpression vectors and siRNAs were used to investigate mechanism of TRAIL sensitivity. GSCs showed greater resistance to TRAIL-induced apoptosis than PGCs and had lower basal caspase activity. Caspase knockdown in PGCs reduced TRAIL sensitivity. Expression levels of c-Fas-associated death domain-like interleukin 1-converting enzyme-like inhibitory protein long and short isoforms (c-FLIPL and c-FLIPS) were significantly higher in GSCs than PGCs, and siRNA-mediated c-FLIP knockdown in GSCs enhanced TRAIL-induced apoptosis. TMZ enhanced TRAIL-induced apoptosis in GSCs and downregulated c-FLIP expression. Add of TMZ also upregulated the expression of the E3 ubiquitin ligase casitas B-lineage lymphoma (c-Cbl). Moreover, overexpression of c-Cbl alone reduced c-FLIP expression, and c-Cbl knockdown both enhanced c-FLIP expression and reduced the potentiating effect of TMZ on TRAIL-induced apoptosis. The result indicated that TMZ may overcome TRAIL resistance in GSCs by suppressing c-FLIP expression through c-Cbl-mediated ubiquitination and degradation. PMID:26142735

  12. High yields of oligodendrocyte lineage cells from human embryonic stem cells at physiological oxygen tensions for evaluation of translational biology.

    PubMed

    Stacpoole, Sybil R L; Spitzer, Sonia; Bilican, Bilada; Compston, Alastair; Karadottir, Ragnhildur; Chandran, Siddharthan; Franklin, Robin J M

    2013-01-01

    We have established and efficient system to specify NG2/PDGF-Rα/OLIG2+ oligodendrocyte precursor cells (OPCs) from human embryonic stem cells (hESCs) at low, physiological (3%) oxygen levels. This was achieved via both forebrain and spinal cord origins, with up to 98% of cells expressing NG2. Developmental insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2 induction via ventral forebrain pathways. The OPCs mature in vitro to express O4 (46%) and subsequently become galactocerebroside (GALC), O1, and myelin basic protein-positive (MBP+) multibranching oligodendrocytes. These were cultured alongside hESC-derived neurons. The electrophysiological properties of human OPCs are similar to those of rat OPCs, with large voltage-gated sodium currents and the ability to fire action potentials. Exposure to a selective retinoid X receptor agonist increased the proportion of O4+ oligodendrocytes that express MBP from 5% to 30%. Thus, we have established a developmentally engineered system to investigate the biological properties of human OPCs and test the effects of putative remyelinating agents prior to clinical application. PMID:24286031

  13. A Multi-Lineage Screen Reveals mTORC1 Inhibition Enhances Human Pluripotent Stem Cell Mesendoderm and Blood Progenitor Production.

    PubMed

    Nazareth, Emanuel Joseph Paul; Rahman, Nafees; Yin, Ting; Zandstra, Peter William

    2016-05-10

    Human pluripotent stem cells (hPSCs) exist in heterogeneous micro-environments with multiple subpopulations, convoluting fate-regulation analysis. We patterned hPSCs into engineered micro-environments and screened responses to 400 small-molecule kinase inhibitors, measuring yield and purity outputs of undifferentiated, neuroectoderm, mesendoderm, and extra-embryonic populations. Enrichment analysis revealed mammalian target of rapamycin (mTOR) inhibition as a strong inducer of mesendoderm. Dose responses of mTOR inhibitors such as rapamycin synergized with Bone Morphogenetic protein 4 (BMP4) and activin A to enhance the yield and purity of BRACHYURY-expressing cells. Mechanistically, small interfering RNA knockdown of RAPTOR, a component of mTOR complex 1, phenocopied the mesendoderm-enhancing effects of rapamycin. Functional analysis during mesoderm and endoderm differentiation revealed that mTOR inhibition increased the output of hemogenic endothelial cells 3-fold, with a concomitant enhancement of blood colony-forming cells. These data demonstrate the power of our multi-lineage screening approach and identify mTOR signaling as a node in hPSC differentiation to mesendoderm and its derivatives. PMID:27132889

  14. Monitoring mixed lineage leukemia expression may help identify patients with mixed lineage leukemia--rearranged acute leukemia who are at high risk of relapse after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Liu, Jing; Wang, Yu; Xu, Lan-Ping; Liu, Dai-Hong; Qin, Ya-Zhen; Chang, Ying-Jun; Liu, Kai-Yan; Huang, Xiao-Jun

    2014-07-01

    To evaluate the prognostic value of the expression of the mixed lineage leukemia (MLL) gene for predicting the relapse of patients with MLL-rearranged acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the levels of MLL transcripts in bone marrow (BM) specimens were monitored serially by real-time quantitative polymerase chain reaction (RQ-PCR) at predetermined time points in 40 patients with MLL-rearranged AL who were treated with allo-HSCT. These patients were followed for a median of 24.5 months (range, 8 to 60 months). A total of 236 BM samples were collected and analyzed. Of these, 230 were monitored concurrently for minimal residual disease (MRD) by flow cytometry (FCM) for leukemia-associated aberrant immune phenotypes and by RQ-PCR for the expression of the Wilms tumor (WT1) gene. The 3-year cumulative incidence of relapse in patients who experienced MLL-positive patients (MLL > .0000%) (n = 9) after HSCT was 93.5% (95% confidence interval [CI], 87% to 100%) compared with 12.5% (95% CI, 5.6% to 19.4%) for MLL-negative patients (n = 31) (P < .001). For these 2 patient groups, the 3-year overall survival (OS) was 12.5% (95% CI, .8% to 24.2%) and 77.8% (95% CI, 68.4% to 87.2%) (P < .001), respectively, and the 3-year leukemia-free survival (LFS) was 0% and 72.2% (95% CI, 61.1% to 83.3%), respectively (P < .001). MLL positivity was associated with a higher rate of relapse (hazard ratio [HR], 18.643; 95% CI, 3.449 to 57.025; P = .001), lower LFS (HR, 7.267; 95% CI, 2.038 to 25.916; P = .002), and lower OS (HR, 8.259; 95% CI, 2.109 to 32.336; P = .002), as determined by Cox multivariate analysis. The expression of the MLL gene had a higher specificity and sensitivity than WT1 or MRD monitored by FCM for predicting the relapse of the patients with MLL + AL. Our results suggest that monitoring the expression of the MLL gene may help to identify patients with MLL + AL who are at high risk of relapse after allo-HSCT and may provide a guide for suitable intervention. PMID:24631740

  15. Differentiation and lineage selection of mouse embryonic stem cells in a stirred bench scale bioreactor with automated process control.

    PubMed

    Schroeder, Magnus; Niebruegge, Sylvia; Werner, Andreas; Willbold, Elmar; Burg, Monika; Ruediger, Manfred; Field, Loren J; Lehmann, Juergen; Zweigerdt, Robert

    2005-12-30

    It is well established that embryonic stem (ES) cells can differentiate into functional cardiomyocytes in vitro. ES-derived cardiomyocytes could be used for pharmaceutical and therapeutic applications, provided that they can be generated in sufficient quantity and with sufficient purity. To enable large-scale culture of ES-derived cells, we have developed a robust and scalable bioprocess that allows direct embryoid body (EB) formation in a fully controlled, stirred 2 L bioreactor following inoculation with a single cell suspension of mouse ES cells. Utilizing a pitched-blade-turbine, parameters for optimal cell expansion as well as efficient ES cell differentiation were established. Optimization of stirring conditions resulted in the generation of high-density suspension cultures containing 12.5 x 10(6) cells/mL after 9 days of differentiation. Approximately 30%-40% of the EBs formed in this process vigorously contracted, indicating robust cardiomyogenic induction. An ES cell clone carrying a recombinant DNA molecule comprised of the cardiomyocyte-restricted alpha myosin heavy chain (alphaMHC) promoter and a neomycin resistance gene was used to establish the utility of this bioprocess to efficiently generate ES-derived cardiomyocytes. The genetically engineered ES cells were cultured directly in the stirred bioreactor for 9 days, followed by antibiotic treatment for another 9 days. The protocol resulted in the generation of essentially pure cardiomyocyte cultures, with a total yield of 1.28 x 10(9) cells in a single 2 L bioreactor run. This study thus provides an important step towards the large-scale generation of ES-derived cells for therapeutic and industrial applications. PMID:16189818

  16. Developmentally Inspired Combined Mechanical and Biochemical Signaling Approach on Zonal Lineage Commitment of Mesenchymal Stem Cells in Articular Cartilage Regeneration

    PubMed Central

    Karimi, Tahereh; Barati, Danial; Karaman, Ozan; Moeinzadeh, Sina; Jabbari, Esmaiel

    2014-01-01

    Articular cartilage is organized into multiple zones including superficial, middle and calcified zones with distinct cellular and extracellular components to impart lubrication, compressive strength, and rigidity for load transmission to bone, respectively. During native cartilage tissue development, changes in biochemical, mechanical, and cellular factors direct the formation of stratified structure of articular cartilage. The objective of this work was to investigate the effect of combined gradients in cell density, matrix stiffness, and zone-specific growth factors on the zonal organization of articular cartilage. Human mesenchymal stem cells (hMSCs) were encapsulated in acrylate-functionalized lactide-chain-extended polyethylene glycol (SPELA) gels simulating cell density and stiffness of the superficial, middle and calcified zones. The cell-encapsulated gels were cultivated in medium supplemented with growth factors specific to each zone and the expression of zone-specific markers was measured with incubation time. Encapsulation of 60×106 cells/mL hMSCs in a soft gel (80 kPa modulus) and cultivation with a combination of TGF-β1 (3 ng/mL) and BMP-7 (100 ng/mL) led to the expression of markers for the superficial zone. Conversely, encapsulation of 15×106 cells/mL hMSCs in a stiff gel (320 MPa modulus) and cultivation with a combination of TGF-β1 (30 ng/mL) and hydroxyapatite (3%) led to the expression of markers for the calcified zone. Further, encapsulation of 20×106 cells/mL hMSCs in a gel with 2.1 MPa modulus and cultivation with a combination of TGF-β1 (30 ng/mL) and IGF-1 (100 ng/mL) led to up-regulation of the middle zone markers. Results demonstrate that a developmental approach with gradients in cell density, matrix stiffness, and zone-specific growth factors can potentially regenerate zonal structure of the articular cartilage. PMID:25387395

  17. Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

    PubMed Central

    Zini, Roberta; Rossi, Lara; Salvestrini, Valentina; Ferrari, Davide; Manfredini, Rossella; Lemoli, Roberto M.

    2013-01-01

    Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions, mostly within the processes of tissue damage and repair and flogosis. We previously demonstrated that adenosine 5?-triphosphate (ATP) inhibits the proliferation of human bone marrow-derived mesenchymal stem cells (BM-hMSCs), while stimulating, in vitro and in vivo, their migration. Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes governing adipogenic and osteoblastic (ie, WNT-pathway-related genes) differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenesis by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPAR? (peroxisome proliferator-activated receptor-gamma). In addition, ATP stimulated osteogenic differentiation by promoting mineralization and expression of the osteoblast-related gene RUNX2 (runt-related transcription factor 2). Furthermore, we demonstrated that ATP stimulated adipogenesis via its triphosphate form, while osteogenic differentiation was induced by the nucleoside adenosine, resulting from ATP degradation induced by CD39 and CD73 ectonucleotidases expressed on the MSC membrane. The pharmacological profile of P2 purinergic receptors (P2Rs) suggests that adipogenic differentiation is mainly mediated by the engagement of P2Y1 and P2Y4 receptors, while stimulation of the P1R adenosine-specific subtype A2B is involved in adenosine-induced osteogenic differentiation. Thus, we provide new insights into molecular regulation of MSC differentiation. PMID:23259837

  18. Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress.

    PubMed

    Illi, Barbara; Scopece, Alessandro; Nanni, Simona; Farsetti, Antonella; Morgante, Liliana; Biglioli, Paolo; Capogrossi, Maurizio C; Gaetano, Carlo

    2005-03-18

    Experimental evidence indicates that shear stress (SS) exerts a morphogenetic function during cardiac development of mouse and zebrafish embryos. However, the molecular basis for this effect is still elusive. Our previous work described that in adult endothelial cells, SS regulates gene expression by inducing epigenetic modification of histones and activation of transcription complexes bearing acetyltransferase activity. In this study, we evaluated whether SS treatment could epigenetically modify histones and influence cell differentiation in mouse embryonic stem (ES) cells. Cells were exposed to a laminar SS of 10 dyne per cm2/s(-1), or kept in static conditions in the presence or absence of the histone deacetylase inhibitor trichostatin A (TSA). These experiments revealed that SS enhanced lysine acetylation of histone H3 at position 14 (K14), as well as serine phosphorylation at position 10 (S10) and lysine methylation at position 79 (K79), and cooperated with TSA, inducing acetylation of histone H4 and phosphoacetylation of S10 and K14 of histone H3. In addition, ES cells exposed to SS strongly activated transcription from the vascular endothelial growth factor (VEGF) receptor 2 promoter. This effect was paralleled by an early induction of cardiovascular markers, including smooth muscle actin, smooth muscle protein 22-alpha, platelet-endothelial cell adhesion molecule-1, VEGF receptor 2, myocyte enhancer factor-2C (MEF2C), and alpha-sarcomeric actin. In this condition, transcription factors MEF2C and Sma/MAD homolog protein 4 could be isolated from SS-treated ES cells complexed with the cAMP response element-binding protein acetyltransferase. These results provide molecular basis for the SS-dependent cardiovascular commitment of mouse ES cells and suggest that laminar flow may be successfully applied for the in vitro production of cardiovascular precursors. PMID:15705964

  19. A boost of BMP4 accelerates the commitment of human embryonic stem cells to the endothelial lineage.

    PubMed

    Goldman, Orit; Feraud, Olivier; Boyer-Di Ponio, Julie; Driancourt, Catherine; Clay, Denis; Le Bousse-Kerdiles, Marie-Caroline; Bennaceur-Griscelli, Annelise; Uzan, Georges

    2009-08-01

    Embryoid bodies (EBs) generated during differentiation of human embryonic stem cells (hESCs) contain vascular-like structures, suggesting that commitment of mesoderm progenitors into endothelial cells occurs spontaneously. We showed that bone morphogenetic protein 4 (BMP4), an inducer of mesoderm, accelerates the peak expression of CD133/kinase insert domain-containing receptor (KDR) and CD144/KDR. Because the CD133(+)KDR(+) population could represent endothelial progenitors, we sorted them at day 7 and cultured them in endothelial medium. These cells were, however, unable to differentiate into endothelial cells. Under standard conditions, the CD144(+)KDR(+) population represents up to 10% of the total cells at day 12. In culture, these cells, if sorted, give rise to a homogeneous population with a morphology typical of endothelial cells and express endothelial markers. These endothelial cells derived from the day 12 sorted population were functional, as assessed by different in vitro assays. When EBs were stimulated by BMP4, the CD144(+)KDR(+) peak was shifted to day 7. Most of these cells, however, were CD31(-), becoming CD31(+) in culture. They then expressed von Willebrand factor and were functional. This suggests that, initially, the BMP4-boosted day 7, CD144(+)KDR(+)CD31(-) population represents immature endothelial cells that differentiate into mature endothelial cells in culture. The expression of OCT3/4, a marker of immaturity for hESCs decreases during EB differentiation, decreasing faster following BMP4 induction. We also show that BMP4 inhibits the global expression of GATA2 and RUNX1, two transcription factors involved in hemangioblast formation, at day 7 and day 12. PMID:19544443

  20. 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).

  1. Better dates for Arctic dinosaurs

    NASA Astrophysics Data System (ADS)

    McKee, Edwin H.; Conrad, James E.; Turin, Brent D.

    The Prince Creek Formation near Ocean Point on the Arctic coastal plain of northern Alaska contains hadrosaur (duck-billed dinosaur) bones, as well as an abundant fauna of mollusks, ostracodes, brachiopods, foraminifers, and palynomorphs. Evaluation of the marine mollusks and ostracodes suggested a Paleocene age for these strata to Marincovich et al. [1985]. A fission-track age on zircon of 50.9 +/- 7.7 Ma from an interbedded tephra [Carter et al., 1977] suggested that they could be as young as early Eocene. If the mollusk, ostracod, and fission-track ages are correct, the hadrosaurs would be of early Cenozoic age—one of the few recorded occurrences of dinosaurs younger than Cretaceous. The foraminifers, pollen, and spores, however, strongly suggest a Late Cretaceous age for their beds [Brouwers et al., 1987].

  2. Extreme convergence in the body plans of an early suchian (Archosauria) and ornithomimid dinosaurs (Theropoda).

    PubMed

    Nesbitt, Sterling J; Norell, Mark A

    2006-05-01

    Living archosaurs comprise birds (dinosaurs) and crocodylians (suchians). The morphological diversity of birds and stem group dinosaurs is tremendous and well-documented. Suchia, the archosaurian group including crocodylians, is generally considered more conservative. Here, we report a new Late Triassic suchian archosaur with unusual, highly specialized features that are convergent with ornithomimid dinosaurs. Several derived features of the skull and postcranial skeleton are identical to conditions in ornithomimids. Such cases of extreme convergence in multiple regions of the skeleton in two distantly related vertebrate taxa are rare. This suggests that these archosaurs show iterative patterns of morphological evolution. It also suggests that this group of suchians occupied the adaptive zone that was occupied by ornithomimosaurs later in the Mesozoic. PMID:16600879

  3. 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 each other. Based on all available data, we introduce a new nomenclature for bird wrist ossifications. PMID:25268520

  4. 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. PMID:23284818

  5. 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. PMID:26023130

  6. 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

  7. 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. PMID:26644579

  8. Children's Tacit and Explicit Understandings of Dinosaurs.

    ERIC Educational Resources Information Center

    Barba, Robertta H.

    The purpose of this cross-age study was to investigate elementary students' (N=120) tacit and explicit understandings of dinosaurs. Detailed analysis of audiotaped interviews of children's performance during a Piagetian-type clinical interview suggests that children's conceptual understandings of dinosaurs are first developed at a tacit level from…

  9. 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

    2012-03-22

    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. PMID:22419156

  10. Advances in cell lineage reprogramming.

    PubMed

    Zhou, Junnian; Yue, Wen; Pei, Xuetao

    2013-03-01

    As a milestone breakthrough of stem cell and regenerative medicine in recent years, somatic cell reprogramming has opened up new applications of regenerative medicine by breaking through the ethical shackles of embryonic stem cells. However, induced pluripotent stem (iPS) cells are prepared with a complicated protocol that results in a low reprogramming rate. To obtain differentiated target cells, iPS cells and embryonic stem cells still need to be induced using step-by-step procedures. The safety of induced target cells from iPS cells is currently a further concerning matter. More broadly conceived is lineage reprogramming that has been investigated since 1987. Adult stem cell plasticity, which triggered interest in stem cell research at the end of the last century, can also be included in the scope of lineage reprogramming. With the promotion of iPS cell research, lineage reprogramming is now considered as one of the most promising fields in regenerative medicine, will hopefully lead to customized, personalized therapeutic options for patients in the future. PMID:23526388

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

    PubMed

    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 degrees 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. PMID:19089398

  12. 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.

  13. The Great Dinosaur Extinction Controversy

    NASA Astrophysics Data System (ADS)

    Glen, William

    In 1980 a scientific upheaval was triggered by the advent of the Alvarez-Berkeley group hypothesis. It explained the death of the dinosaurs and most of the life on Earth 65 million years ago by effects of the impact of a meteorite 10 km wide. Although numerous previous impact hypotheses had been largely ignored, that of the Alvarez group arrested the attention of scientists because it was based on an unprecedented form of evidence: highly anomalous concentrations of platinum group elements in seemingly meteoritic ratios within the pinkie-thick Cretaceous/Tertiary boundary clay.

  14. The Origin and Evolution of Dinosaurs

    NASA Astrophysics Data System (ADS)

    Sereno, Paul C.

    Phylogenetic studies and new fossil evidence have yielded fundamental insights into the pattern and timing of dinosaur evolution and the emergence of functionally modern birds. The dinosaurian radiation began in the Middle Triassic and significantly predates their rise to global dominance by the end of the period. The phylogenetic history of ornithischian and saurichian dinosaurs reveals evolutionary trends such as increasing body size. Adaptations to herbivory dinosaurs were not tightly correlated with marked floral changes. Dinosaurian biogeography during the era of continental breakup principally involved dispersal and regional extinction.

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

    PubMed

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

    2015-06-01

    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

  16. 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

  17. 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 extensive pneumatization of the axial skeleton resulted from the evolution of an avian-style respiratory system, presumably at the base of Saurischia. An avian-style respiratory system would also have lowered the cost of breathing, reduced specific gravity, and may have been important in removing excess body heat. Another crucial innovation inherited from basal dinosaurs was a high BMR. This is required for fueling the high growth rate necessary for a multi-tonne animal to survive to reproductive maturity. The retention of the plesiomorphic oviparous mode of reproduction appears to have been critical as well, allowing much faster population recovery than in megaherbivore mammals. Sauropods produced numerous but small offspring each season while land mammals show a negative correlation of reproductive output to body size. This permitted lower population densities in sauropods than in megaherbivore mammals but larger individuals. Our work on sauropod dinosaurs thus informs us about evolutionary limits to body size in other groups of herbivorous terrestrial tetrapods. Ectothermic reptiles are strongly limited by their low BMR, remaining small. Mammals are limited by their extensive mastication and their vivipary, while ornithsichian dinosaurs were only limited by their extensive mastication, having greater average body sizes than mammals. PMID:21251189

  18. 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 extensive pneumatization of the axial skeleton resulted from the evolution of an avian-style respiratory system, presumably at the base of Saurischia. An avian-style respiratory system would also have lowered the cost of breathing, reduced specific gravity, and may have been important in removing excess body heat. Another crucial innovation inherited from basal dinosaurs was a high BMR. This is required for fueling the high growth rate necessary for a multi-tonne animal to survive to reproductive maturity. The retention of the plesiomorphic oviparous mode of reproduction appears to have been critical as well, allowing much faster population recovery than in megaherbivore mammals. Sauropods produced numerous but small offspring each season while land mammals show a negative correlation of reproductive output to body size. This permitted lower population densities in sauropods than in megaherbivore mammals but larger individuals. Our work on sauropod dinosaurs thus informs us about evolutionary limits to body size in other groups of herbivorous terrestrial tetrapods. Ectothermic reptiles are strongly limited by their low BMR, remaining small. Mammals are limited by their extensive mastication and their vivipary, while ornithsichian dinosaurs were only limited by their extensive mastication, having greater average body sizes than mammals. PMID:21251189

  19. 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)

  20. Palaeoecology: different dinosaur ecologies in deep time?

    PubMed

    Dyke, Gareth J

    2010-11-23

    Do dinosaurs from the Moroccan Kem Kem formation provide evidence for an ecosystem dramatically different from anything seen today? More likely the common palaeontological problem of time-averaging has had a part to play. PMID:21093793

  1. 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

  2. Dinosaur locomotion from a new trackway.

    PubMed

    Day, Julia J; Norman, David B; Upchurch, Paul; Powell, H Philip

    2002-01-31

    Ardley Quarry in Oxfordshire, UK, contains one of the most extensive dinosaur-trackway sites in the world, with individual trackways extending for up to 180 metres. We have discovered a unique dual-gauge trackway from a bipedal theropod dinosaur from the Middle Jurassic in this locality, which indicates that these large theropods were able to run and that they used different hindlimb postures for walking and running. Our findings have implications for the biomechanics and evolution of theropod locomotion. PMID:11823849

  3. 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 dinosaurs and provide the anatomical foundation necessary for future analyses of skull function and evolution in an important vertebrate clade. PMID:19711458

  4. 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! PMID:19711448

  5. 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. PMID:21752814

  6. First Dinosaur Tracks from the Arabian Peninsula

    PubMed Central

    Schulp, Anne S.; Al-Wosabi, Mohammed; Stevens, Nancy J.

    2008-01-01

    Background The evolutionary history of Mesozoic terrestrial vertebrates from the Arabian Peninsula is virtually unknown. Despite vast exposures of rocky outcrops, only a handful of fossils have yet been described from the region. Here we report a multi-taxon dinosaur track assemblage near Madar village, 47 km north of Sana'a, Republic of Yemen. This represents the first dinosaur tracksite from the Arabian Peninsula, and the only multi-taxon dinosaur ichnosite in the Middle East. Methodology/Findings Measurements were taken directly from trackway impressions, following standard ichnological conventions. The presence of bipedal trackmakers is evidenced by a long series of pes imprints preserving smoothly rounded posterior margins, no evidence of a hallux, bluntly rounded digit tips and digital divarication angles characteristic of ornithopod dinosaurs. Nearby, eleven parallel quadrupedal trackways document a sauropod herd that included large and small individuals traveling together. Based on the morphology of manus impressions along with a narrow-gauged stance, the quadrupedal trackways were made by non-titanosauriform neosauropods. Additional isolated tracks and trackways of sauropod and ornithopod dinosaurs are preserved nearby. Conclusions/Significance Taken together, these discoveries present the most evocative window to date into the evolutionary history of dinosaurs of the Arabian Peninsula. Given the limited Mesozoic terrestrial record from the region, this discovery is of both temporal and geographic significance, and massive exposures of similarly-aged outcrops nearby offer great promise for future discoveries. PMID:18493306

  7. 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

  8. 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…

  9. 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…

  10. 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

  11. 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

  12. Temporal and phylogenetic evolution of the sauropod dinosaur body plan.

    PubMed

    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. PMID:27069652

  13. The complete skull and skeleton of an early dinosaur.

    PubMed

    Sereno, P C; Novas, F E

    1992-11-13

    The unearthing of a complete skull and skeleton of the early dinosaur Herrerasaurus ischigualastensis sheds light on the early evolution of dinosaurs. Discovered in the Upper Triassic Ischigualasto Formation of Argentina, the fossils show that Herrerasaurus, a primitive theropod, was an agile, bipedal predator with a short forelimb specialized for grasping and raking. The fossils clarify anatomical features of the common ancestor of all dinosaurs. Herrerasaurus and younger dinosaurs from Upper Triassic beds in Argentina suggest that the dinosaurian radiation was well under way before dinosaurs dominated terrestrial vertebrate communities in taxonomic diversity and abundance. PMID:17789086

  14. Engraftment and Lineage Potential of Adult Hematopoietic Stem and Progenitor Cells Is Compromised Following Short-Term Culture in the Presence of an Aryl Hydrocarbon Receptor Antagonist

    PubMed Central

    Gu, Angel; Torres-Coronado, Monica; Tran, Chy-Anh; Vu, Hieu; Epps, Elizabeth W.; Chung, Janet; Gonzalez, Nancy; Blanchard, Suzette

    2014-01-01

    Abstract Hematopoietic stem cell gene therapy for HIV/AIDS is a promising alternative to lifelong antiretroviral therapy. One of the limitations of this approach is the number and quality of stem cells available for transplant following in vitro manipulations associated with stem cell isolation and genetic modification. The development of methods to increase the number of autologous, gene-modified stem cells available for transplantation would overcome this barrier. Hematopoietic stem and progenitor cells (HSPC) from adult growth factor-mobilized peripheral blood were cultured in the presence of an aryl hydrocarbon receptor antagonist (AhRA) previously shown to expand HSPC from umbilical cord blood. Qualitative and quantitative assessment of the hematopoietic potential of minimally cultured (MC-HSPC) or expanded HSPC (Exp-HSPC) was performed using an immunodeficient mouse model of transplantation. Our results demonstrate robust, multilineage engraftment of both MC-HSPC and Exp-HSPC although estimates of expansion based on stem cell phenotype were not supported by a corresponding increase in in vivo engrafting units. Bone marrow of animals transplanted with either MC-HSPC or Exp-HSPC contained secondary engrafting cells verifying the presence of primitive stem cells in both populations. However, the frequency of in vivo engrafting units among the more primitive CD34+/CD90+ HSPC population was significantly lower in Exp-HSPC compared with MC-HSPC. Exp-HSPC also produced fewer lymphoid progeny and more myeloid progeny than MC-HSPC. These results reveal that in vitro culture of adult HSPC in AhRA maintains but does not increase the number of in vivo engrafting cells and that HSPC expanded in vitro contain defects in lymphopoiesis as assessed in this model system. Further investigation is required before implementation of this approach in the clinical setting. PMID:25003230

  15. Plumage color patterns of an extinct dinosaur.

    PubMed

    Li, Quanguo; Gao, Ke-Qin; Vinther, Jakob; Shawkey, Matthew D; Clarke, Julia A; D'Alba, Liliana; Meng, Qingjin; Briggs, Derek E G; Prum, Richard O

    2010-03-12

    For as long as dinosaurs have been known to exist, there has been speculation about their appearance. Fossil feathers can preserve the morphology of color-imparting melanosomes, which allow color patterns in feathered dinosaurs to be reconstructed. Here, we have mapped feather color patterns in a Late Jurassic basal paravian theropod dinosaur. Quantitative comparisons with melanosome shape and density in extant feathers indicate that the body was gray and dark and the face had rufous speckles. The crown was rufous, and the long limb feathers were white with distal black spangles. The evolution of melanin-based within-feather pigmentation patterns may coincide with that of elongate pennaceous feathers in the common ancestor of Maniraptora, before active powered flight. Feathers may thus have played a role in sexual selection or other communication. PMID:20133521

  16. 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. PMID:23888864

  17. 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.

  18. Scaling effects in theropod dinosaurs

    NASA Astrophysics Data System (ADS)

    Lee, Scott A.

    2014-03-01

    For geometrically similar animals, the length of the leg bones l would scale as the diameter of the leg bone d: d ~ l. In order to maintain the same stresses in the leg bones when standing (i.e., elastic similarity), l3 must scale as d2, yielding d ~ l 3 / 2. Sixty-six femora from more than 30 different species of theropod dinosaurs were studied. Our results yield d ~ l 1 . 16, well below the prediction of elastic similarity. The maximum stresses on the leg bones would have occurred during locomotion when forces on the order of several times the body weight would have been present. Bending and torsional stresses of the femur would have been more likely to break the bone than compression. The ability of the bone to resist bending stresses is given by its section modulus Z. From our data, we find that Z ~ l 3 . 49. The bending torque applied to the femur is expected to scale as roughly l4. Both results indicate that larger theropods had smaller cursorial abilities than smaller theropods, as is observed in extant animals. Assuming that all theropod bones have the same shear modulus, the ability for the femora to resist torsion is given by Q = J/ l where J is the second polar moment of the area. From our data, we find that Q ~ l 3 . 66.

  19. Control of a robot dinosaur

    PubMed Central

    Papantoniou, V.

    1999-01-01

    The Palaiomation Consortium, supported by the European Commission, is building a robot Iguanodon atherfieldensis for museum display that is much more sophisticated than existing animatronic exhibits. The current half-size (2.5 m) prototype is fully autonomous, carrying its own computer and batteries. It walks around the room, choosing its own path and avoiding obstacles. A bigger version with a larger repertoire of behaviours is planned. Many design problems have had to be overcome. A real dinosaur would have had hundreds of muscles, and we have had to devise means of achieving life-like movement with a much smaller number of motors; we have limited ourselves to 20, to keep the control problems manageable. Realistic stance requires a narrower trackway and a higher centre of mass than in previous (often spider-like) legged robots, making it more difficult to maintain stability. Other important differences from previous walking robots are that the forelegs have to be shorter than the hind, and the machinery has had to be designed to fit inside a realistically shaped body shell. Battery life is about one hour, but to achieve this we have had to design the robot to have very low power consumption. Currently, this limits it to unrealistically slow movement. The control system includes a high-level instructions processor, a gait generator, a motion-coordination generator, and a kinematic model.

  20. 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. PMID:26465497

  1. 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.

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

    PubMed

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

    2005-11-01

    The origin of birds and avian flight from within the archosaurian radiation has been among the most contentious issues in paleobiology. Although there is general agreement that birds are related to theropod dinosaurs at some level, debate centers on whether birds are derived directly from highly derived theropods, the current dogma, or from an earlier common ancestor lacking suites of derived anatomical characters. Recent discoveries from the Early Cretaceous of China have highlighted the debate, with claims of the discovery of all stages of feather evolution and ancestral birds (theropod dinosaurs), although the deposits are at least 25 million years younger than those containing the earliest known bird Archaeopteryx. In the first part of the study we examine the fossil evidence relating to alleged feather progenitors, commonly referred to as protofeathers, in these putative ancestors of birds. Our findings show no evidence for the existence of protofeathers and consequently no evidence in support of the follicular theory of the morphogenesis of the feather. Rather, based on histological studies of the integument of modern reptiles, which show complex patterns of the collagen fibers of the dermis, we conclude that "protofeathers" are probably the remains of collagenous fiber "meshworks" that reinforced the dinosaur integument. These "meshworks" of the skin frequently formed aberrant patterns resembling feathers as a consequence of decomposition. Our findings also draw support from new paleontological evidence. We describe integumental structures, very similar to "protofeathers," preserved within the rib area of a Psittacosaurus specimen from Nanjing, China, an ornithopod dinosaur unconnected with the ancestry of birds. These integumental structures show a strong resemblance to the collagenous fiber systems in the dermis of many animals. We also report the presence of scales in the forearm of the theropod ornithomimid (bird mimic) dinosaur, Pelecanimimus, from 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. PMID:16217748

  3. Palaeontology: parental care in an ornithischian dinosaur.

    PubMed

    Meng, Qingjin; Liu, Jinyuan; Varricchio, David J; Huang, Timothy; Gao, Chunling

    2004-09-01

    Crocodilians and birds show extensive parental care of their young, but whether this behaviour evolved independently in these two groups of living archosaurs is unknown - in part because features of parenting among related fossil groups such as dinosaurs are unclear. A dramatic specimen of the small ornithischian dinosaur Psittacosaurus sp. (Dalian Natural History Museum D2156) from Liaoning in China reveals a single adult clustered with 34 juveniles within an area of 0.5 square metres, providing strong evidence for post-hatching parental care in Dinosauria. PMID:15356619

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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. PMID:25688859

  9. New Horned Dinosaurs from Utah Provide Evidence for Intracontinental Dinosaur Endemism

    PubMed Central

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

    2010-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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 latitudinally arrayed evolutionary centers of endemism within chasmosaurine ceratopsids during the late Campanian, the first documented occurrence of intracontinental endemism within dinosaurs. PMID:20877459

  10. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

    PubMed Central

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Sievert, Karl-Dietrich; Skutella, Thomas

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers. PMID:26649052

  11. Conserved loci of leaf and stem rust fungi of wheat share synteny interrupted by lineage-specific influx of repeat elements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Wheat leaf rust (Puccinia triticina Eriks; Pt) and stem rust (P. graminis f.sp. tritici; Pgt) are significant economic pathogens having similar host ranges and life cycles, but different alternate hosts. The Pt genome, currently estimated at 135 Mb, is significantly larger than Pgt, at ...

  12. 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. PMID:24130690

  13. 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

  14. 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

  15. Why Are There No Dinosaurs in Oklahoma?

    ERIC Educational Resources Information Center

    Renner, John W.; And Others

    1981-01-01

    Presents two studies done to identify problems students have in understanding the concepts of Darwinian evolution and adaptation. Results indicated poor understanding of the concept of time accounted for misconceptions in both studies (humans destroyed dinosaurs), and that only about 50 percent of students used logical reasoning. (JN)

  16. Dinosaur diversity and the rock record.

    PubMed

    Barrett, Paul M; McGowan, Alistair J; Page, Victoria

    2009-07-22

    Palaeobiodiversity analysis underpins macroevolutionary investigations, allowing identification of mass extinctions and adaptive radiations. However, recent large-scale studies on marine invertebrates indicate that geological factors play a central role in moulding the shape of diversity curves and imply that many features of such curves represent sampling artefacts, rather than genuine evolutionary events. In order to test whether similar biases affect diversity estimates for terrestrial taxa, we compiled genus-richness estimates for three Mesozoic dinosaur clades (Ornithischia, Sauropodomorpha and Theropoda). Linear models of expected genus richness were constructed for each clade, using the number of dinosaur-bearing formations available through time as a proxy for the amount of fossiliferous rock outcrop. Modelled diversity estimates were then compared with observed patterns. Strong statistically robust correlations demonstrate that almost all aspects of ornithischian and theropod diversity curves can be explained by geological megabiases, whereas the sauropodomorph record diverges from modelled predictions and may be a stronger contender for identifying evolutionary signals. In contrast to other recent studies, we identify a marked decline in dinosaur genus richness during the closing stages of the Cretaceous Period, indicating that the clade decreased in diversity for several million years prior to the final extinction of non-avian dinosaurs at the Cretaceous-Palaeocene boundary. PMID:19403535

  17. Dinosaur diversity and the rock record

    PubMed Central

    Barrett, Paul M.; McGowan, Alistair J.; Page, Victoria

    2009-01-01

    Palaeobiodiversity analysis underpins macroevolutionary investigations, allowing identification of mass extinctions and adaptive radiations. However, recent large-scale studies on marine invertebrates indicate that geological factors play a central role in moulding the shape of diversity curves and imply that many features of such curves represent sampling artefacts, rather than genuine evolutionary events. In order to test whether similar biases affect diversity estimates for terrestrial taxa, we compiled genus-richness estimates for three Mesozoic dinosaur clades (Ornithischia, Sauropodomorpha and Theropoda). Linear models of expected genus richness were constructed for each clade, using the number of dinosaur-bearing formations available through time as a proxy for the amount of fossiliferous rock outcrop. Modelled diversity estimates were then compared with observed patterns. Strong statistically robust correlations demonstrate that almost all aspects of ornithischian and theropod diversity curves can be explained by geological megabiases, whereas the sauropodomorph record diverges from modelled predictions and may be a stronger contender for identifying evolutionary signals. In contrast to other recent studies, we identify a marked decline in dinosaur genus richness during the closing stages of the Cretaceous Period, indicating that the clade decreased in diversity for several million years prior to the final extinction of non-avian dinosaurs at the Cretaceous–Palaeocene boundary. PMID:19403535

  18. 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…

  19. 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

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

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

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

  1. Dinosaur morphological diversity and the end-Cretaceous extinction.

    PubMed

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

    2012-01-01

    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. PMID:22549833

  2. Derivation of Mesenchymal Stromal Cells from Pluripotent Stem Cells through a Neural Crest Lineage using Small Molecule Compounds with Defined Media

    PubMed Central

    Nakagawa, Masato; Sekiguchi, Kazuya; Nagata, Sanae; Matsumoto, Yoshihisa; Yamamoto, Takuya; Umeda, Katsutsugu; Heike, Toshio; Okumura, Naoki; Koizumi, Noriko; Sato, Takahiko; Nakahata, Tatsutoshi; Saito, Megumu; Otsuka, Takanobu; Kinoshita, Shigeru; Ueno, Morio; Ikeya, Makoto; Toguchida, Junya

    2014-01-01

    Neural crest cells (NCCs) are an embryonic migratory cell population with the ability to differentiate into a wide variety of cell types that contribute to the craniofacial skeleton, cornea, peripheral nervous system, and skin pigmentation. This ability suggests the promising role of NCCs as a source for cell-based therapy. Although several methods have been used to induce human NCCs (hNCCs) from human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), further modifications are required to improve the robustness, efficacy, and simplicity of these methods. Chemically defined medium (CDM) was used as the basal medium in the induction and maintenance steps. By optimizing the culture conditions, the combination of the GSK3β inhibitor and TGFβ inhibitor with a minimum growth factor (insulin) very efficiently induced hNCCs (70–80%) from hPSCs. The induced hNCCs expressed cranial NCC-related genes and stably proliferated in CDM supplemented with EGF and FGF2 up to at least 10 passages without changes being observed in the major gene expression profiles. Differentiation properties were confirmed for peripheral neurons, glia, melanocytes, and corneal endothelial cells. In addition, cells with differentiation characteristics similar to multipotent mesenchymal stromal cells (MSCs) were induced from hNCCs using CDM specific for human MSCs. Our simple and robust induction protocol using small molecule compounds with defined media enabled the generation of hNCCs as an intermediate material producing terminally differentiated cells for cell-based innovative medicine. PMID:25464501

  3. STEM?!?!

    ERIC Educational Resources Information Center

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  4. No statistical support for sudden (or gradual) extinction of dinosaurs

    NASA Astrophysics Data System (ADS)

    Hurlbert, Stuart H.; Archibald, J. David

    1995-10-01

    Did dinosaurs decline gradually or abruptly at the Cretaceous-Tertiary boundary? An analysis of familial diversity patterns in dinosaur fossils from the Hell Creek Formation of central North America has claimed to present strong statistical evidence against the idea that dinosaurs declined gradually near the end of the Cretaceous. Examination of the quantitative methodologies used shows that these provide no basis for choosing between scenarios of abrupt extinction and gradual decline.

  5. Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes

    PubMed Central

    Bemark, M; Holmqvist, J; Abrahamsson, J; Mellgren, K

    2012-01-01

    OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON B CELL SUBSETS IN DISEASE B cells in multiple sclerosis: drivers of disease pathogenesis and Trojan horse for Epstein—Barr virus entry to the central nervous system? Clinical and Experimental Immunology 2012, 167: 1–6. Transitional B cells in systemic lupus erythematosus and Sjögren's syndrome: clinical implications and effects of B cell-targeted therapies. Clinical and Experimental Immunology 2012, 167: 7–14. Haematopoietic stem cell transplantation (HSCT) is an immunological treatment that has been used for more than 40 years to cure a variety of diseases. The procedure is associated with serious side effects, due to the severe impairment of the immune system induced by the treatment. After a conditioning regimen with high-dose chemotherapy, sometimes in combination with total body irradiation, haematopoietic stem cells are transferred from a donor, allowing a donor-derived blood system to form. Here, we discuss the current knowledge of humoral problems and B cell development after HSCT, and relate these to the current understanding of human peripheral B cell development. We describe how these studies have aided the identification of subsets of transitional B cells and also a robust memory B cell phenotype. PMID:22132880

  6. Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/β-catenin signaling pathway.

    PubMed

    Guan, Junjie; Zhang, Jieyuan; Guo, Shangchun; Zhu, Hongyi; Zhu, Zhenzhong; Li, Haiyan; Wang, Yang; Zhang, Changqing; Chang, Jiang

    2015-07-01

    Human urine-derived stem cells (USCs) have great application potential for cytotherapy as they can be obtained by non-invasive and simple methods. Silicate bioceramics, including calcium silicate (CS), can stimulate osteogenic differentiation of stem cells. However, the effects of silicate bioceramics on osteogenic differentiation of USCs have not been reported. In this study, at first, we investigated the effects of CS ion extracts on proliferation and osteogenic differentiation of USCs, as well as the related mechanism. CS particles were incorporated into poly (lactic-co-glycolic acid) (PLGA) to obtain PLGA/CS composite scaffolds. USCs were then seeded onto these scaffolds, which were subsequently transplanted into nude mice to analyze the osteogenic differentiation of USCs and mineralization of extracellular matrix formed by USCs in vivo. The results showed that CS ion extracts significantly enhanced cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and expression of certain osteoblast-related genes and proteins. In addition, cardamonin, a Wnt/β-catenin signaling inhibitor, reduced the stimulatory effects of CS ion extracts on osteogenic differentiation of USCs, indicating that the observed osteogenic differentiation of USCs induced by CS ion extracts involves Wnt/β-catenin signaling pathway. Furthermore, histological analysis showed that PLGA/CS composite scaffolds significantly enhanced the osteogenic differentiation of USCs in vivo. Taken together, these results suggest the therapeutic potential of combining USCs and PLGA/CS scaffolds in bone tissue regeneration. PMID:25934447

  7. A new probable stem lineage crustacean with three-dimensionally preserved soft parts from the Herefordshire (Silurian) Lagerstätte, UK.

    PubMed

    Siveter, Derek J; Sutton, Mark D; Briggs, Derek E G; Siveter, David J

    2007-09-01

    A new arthropod with three-dimensionally preserved soft parts, Tanazios dokeron, is described from the Wenlock Series (Silurian) of Herefordshire, England, UK. Serial grinding, digital photographic and computer rendering techniques yielded 'virtual fossils' in the round for study. The body tagmata of T. dokeron comprise a head shield and a long trunk. The head shield bears six pairs of horn-like spines and the head bears five pairs of appendages. The antennule, antenna and mandible are all uniramous, and the mandible includes a gnathobasic coxa. Appendages four and five are biramous and similar to those of the trunk: each comprises a limb base with an endite, an enditic membrane, and two epipodites, plus an endopod and exopod. The hypostome bears a large cone-like projection centrally, and there may be a short labrum. The trunk has some 64 segments and at least 60 appendage pairs. A very small telson has the anus sited ventrally in its posterior part and also bears a caudal furca. Comparative morphological and cladistic analyses of T. dokeron indicate a crustacean affinity, with a probable position in the eucrustacean stem group. As such the epipodites in T. dokeron are the first recorded in a eucrustacean stem taxon. The new species is interpreted as a benthic or nektobenthic scavenger. PMID:17609185

  8. Promoter and lineage independent anti-silencing activity of the A2 ubiquitous chromatin opening element for optimized human pluripotent stem cell-based gene therapy.

    PubMed

    Ackermann, Mania; Lachmann, Nico; Hartung, Susann; Eggenschwiler, Reto; Pfaff, Nils; Happle, Christine; Mucci, Adele; Ghring, Gudrun; Niemann, Heiner; Hansen, Gesine; Schambach, Axel; Cantz, Tobias; Zweigerdt, Robert; Moritz, Thomas

    2014-02-01

    Epigenetic silencing of retroviral transgene expression in pluripotent stem cells (PSC) and their differentiated progeny constitutes a major roadblock for PSC-based gene therapy. As ubiquitous chromatin opening elements (UCOEs) have been successfully employed to stabilize transgene expression in murine hematopoietic and pluripotent stem cells as well as their differentiated progeny, we here investigated UCOE activity in their human counterparts to establish a basis for future clinical application of the element. To this end, we demonstrate profound anti-silencing activity of the A2UCOE in several human iPS and ES cell lines including their progeny obtained upon directed cardiac or hematopoietic differentiation. We also provide evidence for A2UCOE activity in murine iPSC-derived hepatocyte-like cells, thus establishing efficacy of the element in cells of different germ layers. Finally, we investigated combinations of the A2UCOE with viral promoter/enhancer elements again demonstrating profound stabilization of transgene expression. In all these settings the effect of the A2UCOE was associated with strongly reduced promoter DNA-methylation. Thus, our data clearly support the concept of the A2UCOE as a generalized strategy to prevent epigenetic silencing in PSC and their differentiated progeny and strongly favors its application to stabilize transgene expression in PSC-based cell and gene therapy approaches. PMID:24290698

  9. Chromatin Remodeling Factor Brg1 Supports the Early Maintenance and Late Responsiveness of Nestin-Lineage Adult Neural Stem and Progenitor Cells.

    PubMed

    Petrik, David; Latchney, Sarah E; Masiulis, Irene; Yun, Sanghee; Zhang, Zilai; Wu, Jiang I; Eisch, Amelia J

    2015-12-01

    Insights from embryonic development suggest chromatin remodeling is important in adult neural stem cells (aNSCs) maintenance and self-renewal, but this concept has not been fully explored in the adult brain. To assess the role of chromatin remodeling in adult neurogenesis, we inducibly deleted Brg1-the core subunit of SWI/SNF-like Brg1/Brm-associated factor chromatin remodeling complexes-in nestin-expressing aNSCs and their progeny in vivo and in culture. This resulted in abnormal adult neurogenesis in the hippocampus, which initially reduced hippocampal aNSCs and progenitor maintenance, and later reduced its responsiveness to physiological stimulation. Mechanistically, deletion of Brg1 appeared to impair cell cycle progression, which is partially due to elevated p53 pathway and p21 expression. Knockdown of p53 rescued the neurosphere growth defects caused by Brg1 deletion. Our results show that epigenetic chromatin remodeling (via a Brg1 and p53/p21-dependent process) determines the aNSCs and progenitor maintenance and responsiveness of neurogenesis. Stem Cells 2015;33:3655-3665. PMID:26418130

  10. Stable-isotope analyses of dinosaur eggshells: Paleoenvironmental implications

    NASA Astrophysics Data System (ADS)

    Sarkar, A.; Bhattacharya, S. K.; Mohabey, D. M.

    1991-11-01

    Well-preserved clutches of dinosaur (sauropod) eggshells and skeletal remains have been discovered in the Upper Cretaceous Lameta limestones of the Kheda district, Gujarat, India, indicating a dinosaur nesting site. Oxygen-isotope analyses of the eggs show that the dinosaurs drank from a variety of freshwater bodies such as rivers and small evaporative pools, whereas the carbon-isotope values indicate that the reptiles were consuming plants that utilize the C3 photosynthetic pathway, e.g., small palms, shrubs, conifers, etc. Similar analyses of the host limestones suggest that they were deposited in a freshwater environment that provided the niche for large-scale breeding and nesting of the dinosaurs.

  11. The second Jurassic dinosaur rush and the dawn of dinomania.

    PubMed

    Brinkman, Paul D

    2010-09-01

    During the second Jurassic dinosaur rush museum paleontologists raced to display the world's first mounted sauropod dinosaur. The American Museum of Natural History triumphed in 1905 when its Brontosaurus debuted before an admiring crowd of wealthy New Yorkers. The Carnegie Museum of Natural History in Pittsburgh, the Field Columbian Museum in Chicago and other institutions were quick to follow with their own sauropod displays. Thereafter, dinomania spread far and wide, and big, showpiece dinosaurs became a museum staple. This brief but intensely competitive period of acquisitiveness fostered important Jurassic dinosaur revisions and crucial innovations in paleontological field and lab techniques. PMID:20667597

  12. Yeosu dinosaur track sites of Korea: The youngest dinosaur track records in Asia

    NASA Astrophysics Data System (ADS)

    Paik, In Sung; Huh, Min; Park, Kye Hun; Hwang, Koo Geun; Kim, Kyung Sik; Kim, Hyun Joo

    2006-12-01

    Eighty two dinosaur trackways were newly discovered in Upper Cretaceous lacustrine deposits on islands in the vicinity of Yeosu, Korea. Most dinosaur tracks occur in marginal lake deposits with polygonal desiccation cracks. The dinosaur tracks at the Yeosu site include 65 ornithopod trackways, 16 theropod trackways and one sauropod trackway. The prevalence of ornithopod tracks and the limited occurrence of sauropod tracks at the Yeosu site evidently reflect decreased sauropod diversity in the Upper Cretaceous. All ornithopod trackways represent bipeds, and most of the ornithopod tracks are similar to Caririchnium from other sites of the Korean peninsula. All fossil wood specimens collected in the study area represent conifers (three species of cupressaceous and two species of taxodiaceous conifers, and a new species) except for one, which is a discotyledon. It is thus inferred that the southwestern part of the Korean Peninsula was primarily covered with mesic forests with taxodiaceous trees during the Late Cretaceous. The K-Ar age of the Yeosu tracksite is determined as 81-65 Ma (Camapnian to Maastrichtian). It indicates that the Yeosu track site contains the last records of dinosaurs living in Asia. Consequently, semi-arid palaeoclimatic conditions, together with a large lake as a persistent water source and rich vegetation of gymnosperm trees as food, resulted in the preservation of abundant dinosaur tracks in the Upper Cretaceous on the Korean Peninsula.

  13. Locomotion speeds from trackways: Predatory dinosaurs moved faster than herbivorous dinosaurs

    NASA Astrophysics Data System (ADS)

    Lee, Scott A.

    2014-03-01

    Fossilized trackways from dinosaurs leaves evidence of their locomotion from the stride length S and foot length F which yields the leg length L. From studies of living animals, it is known that a walking animal has a relative stride length RSL (= S/L) less than 2 and a running animal has a RSL greater than 2. A statistical analysis was performed of trackways associated with three groups of herbivorous dinosaurs: sauropods (N = 23), the armored ankylosaurs and stegosaurs (N = 10), and the unarmored ornithopods (N = 23) as well as the predatory theropods (N = 35). The average RSL of the sauropods and the armored dinosaurs were both 0.9 +/- 0.3. The ornithopods had an average RSL of 1.2 +/- 0.2. None of the trackways associated with herbivorous dinosaurs have an RSL greater than 1.5, indicating that they were all walking. The theropods showed the fastest and most varied locomomtion: their highest average RSL was 1.8 +/- 0.7. Nine of the theropod trackways had an RSL greater than 2.0, indicating that the dinosaurs were running when they made those trackways. One of the theropod trackways had an RSL of 4.5, indicating that it was running very fast compared to its body length.

  14. Expansion on Extracellular Matrix Deposited by Human Bone Marrow Stromal Cells Facilitates Stem Cell Proliferation and Tissue-Specific Lineage Potential

    PubMed Central

    He, Fan; Kish, Vincent L.

    2011-01-01

    Our objective was to assess the rejuvenation effect of extracellular matrix (ECM) deposited by human bone marrow stromal cells (hBMSCs) on hBMSC expansion and tissue-specific lineage differentiation potential. Passage 5 hBMSCs were expanded on ECM or conventional plastic flasks (Plastic) for one passage. Cell number was counted and immunophenotype profiles were assessed using flow cytometry. Selected integrins and proliferation-related pathway signals were assessed using Western blot. The expanded cells were evaluated for their chondrogenic potential in a pellet culture system with TGF-β3-containing chondrogenic medium using gross morphology, histology, immunostaining, biochemical analysis, real-time polymerase chain reaction, Western blot, and biomechanical testing. ECM-expanded hBMSCs were further evaluated for their osteogenic potential using Alizarin Red S staining and alkaline phosphatase activity assay and for their adipogenic potential using Oil Red O staining. ECM-expanded hBMSCs exhibited an enhanced proliferation capacity and an acquired robust chondrogenic potential compared to those grown on Plastic. ECM expansion decreased intracellular reactive oxygen species and increased stage-specific embryonic antigen-4 expression in hBMSCs. ECM expansion also upregulated integrins α2 and β5 and induced a sustained activation of Erk1/2 and cyclin D1. Interestingly, upregulation of TGF-β receptor II during cell expansion and chondrogenic induction might be responsible for an enhanced chondrogenic potential in ECM-expanded hBMSCs. We also found that ECM-expanded hBMSCs had an increased osteogenic potential and decreased adipogenic capacity. ECM deposited by hBMSCs may be a promising approach to expand BMSCs from elderly patients for the treatment of large-scale bone defects through endochondral bone formation. PMID:21740327

  15. Single-cell lineage tracking analysis reveals that an established cell line comprises putative cancer stem cells and their heterogeneous progeny

    PubMed Central

    Sato, Sachiko; Rancourt, Ann; Sato, Yukiko; Satoh, Masahiko S.

    2016-01-01

    Mammalian cell culture has been used in many biological studies on the assumption that a cell line comprises putatively homogeneous clonal cells, thereby sharing similar phenotypic features. This fundamental assumption has not yet been fully tested; therefore, we developed a method for the chronological analysis of individual HeLa cells. The analysis was performed by live cell imaging, tracking of every single cell recorded on imaging videos, and determining the fates of individual cells. We found that cell fate varied significantly, indicating that, in contrast to the assumption, the HeLa cell line is composed of highly heterogeneous cells. Furthermore, our results reveal that only a limited number of cells are immortal and renew themselves, giving rise to the remaining cells. These cells have reduced reproductive ability, creating a functionally heterogeneous cell population. Hence, the HeLa cell line is maintained by the limited number of immortal cells, which could be putative cancer stem cells. PMID:27003384

  16. Single-cell lineage tracking analysis reveals that an established cell line comprises putative cancer stem cells and their heterogeneous progeny.

    PubMed

    Sato, Sachiko; Rancourt, Ann; Sato, Yukiko; Satoh, Masahiko S

    2016-01-01

    Mammalian cell culture has been used in many biological studies on the assumption that a cell line comprises putatively homogeneous clonal cells, thereby sharing similar phenotypic features. This fundamental assumption has not yet been fully tested; therefore, we developed a method for the chronological analysis of individual HeLa cells. The analysis was performed by live cell imaging, tracking of every single cell recorded on imaging videos, and determining the fates of individual cells. We found that cell fate varied significantly, indicating that, in contrast to the assumption, the HeLa cell line is composed of highly heterogeneous cells. Furthermore, our results reveal that only a limited number of cells are immortal and renew themselves, giving rise to the remaining cells. These cells have reduced reproductive ability, creating a functionally heterogeneous cell population. Hence, the HeLa cell line is maintained by the limited number of immortal cells, which could be putative cancer stem cells. PMID:27003384

  17. Bioinspired Quercitrin Nanocoatings: A Fluorescence-Based Method for Their Surface Quantification, and Their Effect on Stem Cell Adhesion and Differentiation to the Osteoblastic Lineage.

    PubMed

    Córdoba, Alba; Monjo, Marta; Hierro-Oliva, Margarita; González-Martín, María Luisa; Ramis, Joana Maria

    2015-08-01

    Polyphenol-based coatings have several potential applications in medical devices, such as cardiovascular stents, contrast agents, drug delivery systems, or bone implants, due to the multiple bioactive functionalities of these compounds. In a previous study, we fabricated titanium surfaces functionalized with flavonoids through covalent chemistry, and observed their osteogenic, anti-inflammatory, and antifibrotic properties in vitro. In this work, we report a fluorescence-based method for the quantification of the amount of flavonoid grafted onto the surfaces, using 2-aminoethyl diphenylborinate, a boronic ester that spontaneously forms a fluorescent complex with flavonoids. The method is sensitive, simple, rapid, and easy to perform with routine equipment, and could be applied to determine the surface coverage of other plant-derived polyphenol-based coatings. Besides, we evaluated an approach based on reductive amination to covalently graft the flavonoid quercitrin to Ti substrates, and optimized the grafting conditions. Depending on the reaction conditions, the amount of quercitrin grafted was between 64 ± 10 and 842 ± 361 nmol on 6.2 mm Ti coins. Finally, we evaluated the in vitro behavior of bone-marrow-derived human mesenchymal stem cells cultured on the quercitrin nanocoated Ti surfaces. The surfaces functionalized with quercitrin showed a faster stem cell adhesion than control surfaces, probably due to the presence of the catechol groups of quercitrin on the surfaces. A rapid cell adhesion is crucial for the successful performance of an implant. Furthermore, quercitrin-nanocoated surfaces enhanced the mineralization of the cells after 21 days of cell culture. These results indicate that quercitrin nanocoatings could promote the rapid osteointegration of bone implants. PMID:26167954

  18. Pax6 Is Essential for the Maintenance and Multi-Lineage Differentiation of Neural Stem Cells, and for Neuronal Incorporation into the Adult Olfactory Bulb

    PubMed Central

    Curto, Gloria G.; Nieto-Estévez, Vanesa; Hurtado-Chong, Anahí; Valero, Jorge; Gómez, Carmela; Alonso, José R.; Weruaga, Eduardo

    2014-01-01

    The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/SeyDey mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we assessed its influence on neural differentiation, neuronal incorporation, and cell death in the adult OB, both in vivo and in vitro. Our results indicate that the Pax6 mutation alters Nestin+-cell proliferation in vivo, as well as self-renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation of +/SeyDey progenitors is able to expand partially similar to wild-type progenitors. This mutation also impairs aOBSC differentiation into neurons and oligodendrocytes, whereas it increases cell death while preserving astrocyte survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction in the variety of neurochemical interneuron subtypes generated from aOBSCs in vitro and in the incorporation of newly generated neurons into the OB in vivo. Our findings support an important role of Pax6 in the maintenance of aOBSCs by regulating cell death, self-renewal, and cell fate, as well as in neuronal incorporation into the adult OB. They also suggest that deregulation of the cell cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at the origin of the phenotypes observed in this adult NSC population. PMID:25117830

  19. Electrical and neurotransmitter activity of mature neurons derived from mouse embryonic stem cells by Sox-1 lineage selection and directed differentiation.

    PubMed

    Lang, R J; Haynes, J M; Kelly, J; Johnson, J; Greenhalgh, J; O'brien, C; Mulholland, E M; Baker, L; Munsie, M; Pouton, C W

    2004-12-01

    Sx1TV2/16C is a mouse embryonic stem (ES) cell line in which one copy of the Sox1 gene, an early neuroectodermal marker, has been targeted with a neomycin (G418) selection cassette. A combination of directed differentiation with retinoic acid and G418 selection results in an enriched neural stem cell population that can be further differentiated into neurons. After 6-7 days post-plating (D6-7PP) most neurons readily fired tetrodotoxin (TTX)-sensitive action potentials due to the expression of TTX-sensitive Na(+) and tetraethylammonium (TEA)-sensitive K(+) channels. Neurons reached their maximal cell capacitance after D6-7PP; however, ion channel expression continued until at least D21PP. The percentage of cells receiving spontaneous synaptic currents (s.s.c.) increased with days in culture until 100% of cells received a synaptic input by D20PP. Spontaneous synaptic currents were reduced in amplitude and frequency by TTX, or upon exposure to a Ca(2+)-free, 2.5 mm Mg(2+) saline. S.s.c. of rapid decay time constants were preferentially blocked by the nonNMDA glutamatergic receptor antagonists CNQX or NBQX. Ca(2+) levels within ES cell-derived neurons increased in response to glutamate receptor agonists l-glutamate, AMPA, N-methyl-d-aspartate (NMDA) and kainic acid and to acetylcholine, ATP and dopamine. ES cell-derived neurons also generated cationic and Cl(-)-selective currents in response to NMDA and glycine or GABA, respectively. It was concluded that ES-derived neurons fire action potentials, receive excitatory and inhibitory synaptic input and respond to various neurotransmitters in a manner akin to primary central neurons. PMID:15610154

  20. Feather quill knobs in the dinosaur Velociraptor.

    PubMed

    Turner, Alan H; Makovicky, Peter J; Norell, Mark A

    2007-09-21

    Some nonavian theropod dinosaurs were at least partially covered in feathers or filamentous protofeathers. However, a complete understanding of feather distribution among theropod dinosaurs is limited because feathers are typically preserved only in lagerstätten like that of Solnhofen, Germany or Liaoning, China. Such deposits possess clear taphonomic biases toward small-bodied animals, limiting our knowledge regarding feather presence in larger members of feathered clades. We present direct evidence of feathers in Velociraptor mongoliensis based on the presence of quill knobs on the posterior forearm. This report of secondaries in a larger-bodied, derived, and clearly flightless member of a nonavian theropod clade represented by feathered relatives is a substantial contribution to our knowledge of the evolution of feathers. PMID:17885130

  1. 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

  2. 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. PMID:23874409

  3. The rod photoreceptor lineage of teleost fish.

    PubMed

    Stenkamp, Deborah L

    2011-11-01

    The retinas of postembryonic teleost fish continue to grow for the lifetime of the fish. New retinal cells are added continuously at the retinal margin, by stem cells residing at the circumferential germinal zone. Some of these retinal cells differentiate as Müller glia with cell bodies that reside within the inner nuclear layer. These glia retain some stem cell properties in that they carry out asymmetric cell divisions and continuously generate a population of transit-amplifying cells--the rod photoreceptor lineage--that are committed to rod photoreceptor neurogenesis. These rod progenitors progress through a stereotyped sequence of changes in gene expression as they continue to divide and migrate to the outer nuclear layer. Now referred to as rod precursors, they undergo terminal mitoses and then differentiate as rods, which are inserted into the existing array of rod and cone photoreceptors. The rod lineage displays developmental plasticity, as rod precursors can respond to the loss of rods through increased proliferation, resulting in rod replacement. The stem cells of the rod lineage, Müller glia, respond to acute damage of other retinal cell types by increasing their rate of proliferation. In addition, the Müller glia in an acutely damaged retina dedifferentiate and become multipotent, generating new, functional neurons. This review focuses on the cells of the rod lineage and includes discussions of experiments over the last 30 years that led to their identification and characterization, and the discovery of the stem cells residing at the apex of the lineage. The plasticity of cells of the rod lineage, their relationships to cone progenitors, and the applications of this information for developing future treatments for human retinal disorders will also be discussed. PMID:21742053

  4. Hanford: The evolution of a dinosaur

    SciTech Connect

    Fulton, J.

    1995-11-01

    This article describes how the Westinghouse Hanford Company is reinventing the US DOE`s Hanford Site, turning a 1940s-era dinosaur into a 1990s-style business. The major topics covered include the following: breaking the logjam by ending the inefficient cost-plus days; Concentrating resources on resolving urgent safety issues; contract reform with more incentive, greater risk; finally reengineering: the next step.

  5. Sp1 Transcription Factor Interaction with Accumulated Prelamin A Impairs Adipose Lineage Differentiation in Human Mesenchymal Stem Cells: Essential Role of Sp1 in the Integrity of Lipid Vesicles

    PubMed Central

    Ruiz de Eguino, Garbiñe; Infante, Arantza; Schlangen, Karin; Aransay, Ana M.; Fullaondo, Ane; Soriano, Mario; García-Verdugo, José Manuel; Martín, Ángel G.

    2012-01-01

    Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, metabolic alterations, and early cardiovascular complications. Both LMNA-linked lipodystrophies are characterized by the accumulation of the lamin A precursor prelamin A. The pathological mechanism by which prelamin A accumulation induces the lipodystrophy associated phenotypes remains unclear. Since the affected tissues in these disorders are of mesenchymal origin, we have generated an LMNA-linked experimental model using human mesenchymal stem cells treated with a PI, which recapitulates the phenotypes observed in patient biopsies. This model has been demonstrated to be a useful tool to unravel the pathological mechanism of the LMNA-linked lipodystrophies, providing an ideal system to identify potential targets to generate new therapies for drug discovery screening. We report for the first time that impaired adipogenesis is a consequence of the interaction between accumulated prelamin A and Sp1 transcription factor, sequestration of which results in altered extracellular matrix gene expression. In fact, our study shows a novel, essential, and finely tuned role for Sp1 in adipose lineage differentiation in human mesenchymal stem cells. These findings define a new physiological experimental model to elucidate the pathological mechanisms LMNA-linked lipodystrophies, creating new opportunities for research and treatment not only of LMNA-linked lipodystrophies but also of other adipogenesis-associated metabolic diseases. PMID:23197810

  6. Cannibalism in the Madagascan dinosaur Majungatholus atopus.

    PubMed

    Rogers, Raymond R; Krause, David W; Curry Rogers, Kristina

    2003-04-01

    Many lines of evidence have been brought to bear on the question of theropod feeding ecology, including functional and physiological considerations, morphological constraints, taphonomic associations, and telling--although rare--indications of direct ingestion. Tooth marks of theropods, although rarely described and generally left unassigned to a particular taxon, can provide unique clues into predator-prey interaction, and can also yield insights into the extent of carcass utilization. Here we describe a sample of tooth-marked dinosaur bone recovered from three well-documented localities in the Upper Cretaceous Maevarano Formation of Madagascar that provides insights into the feeding ecology of the abelisaurid theropod Majungatholus atopus. Intensely tooth-marked elements from multiple individuals show that Majungatholus defleshed dinosaur carcasses. Furthermore, Majungatholus clearly fed upon the remains of not only sauropods, but also conspecifics, and thus was a cannibal. Cannibalism is a common ecological strategy among extant carnivores, but until now the evidence in relation to carnivorous dinosaurs has been sparse and anecdotal. PMID:12673249

  7. 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

  8. 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

  9. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    SciTech Connect

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

    2011-09-16

    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.

  10. 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

  11. A factor(s) secreted from MIN-6 beta-cells stimulates differentiation of definitive endoderm enriched embryonic stem cells towards a pancreatic lineage.

    PubMed

    Uroi?, Daniela S; Baudouin, Grgory; Ferguson, Laura A; Docherty, Hilary M; Vallier, Ludovic; Docherty, Kevin

    2010-10-26

    In the mouse the developing pancreas is controlled by contact with, and signalling molecules secreted from, surrounding cells. These factors are best studied using explant cultures of embryonic tissue. The present study was undertaken to determine whether embryonic stem (ES) cells could be used as an alternative model in vitro system to investigate the role of cell-cell interactions in the developing pancreas. Transwell culture experiments showed that MIN-6 beta-cells secreted a factor or factors that promoted differentiation of ES cell derived definitive endoderm enriched cells towards a pancreatic fate. Further studies using MIN-6 condition medium showed that the factor(s) involved was restricted to MIN-6 cells, could be concentrated with ammonium sulphate, and was sensitive to heat treatment, suggesting that it was a protein or peptide. Further analyses showed that insulin or proinsulin failed to mimic the effects of the conditioned media. Collectively, these results suggest that beta-cells secrete a factor(s) capable of controlling their own differentiation and maturation. The culture system described here presents unique advantages in the identification and characterisation of these factors. PMID:20674663

  12. 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 scarabaeine dung beetles and provide examples. PMID:27145126

  13. 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 scarabaeine dung beetles and provide examples. PMID:27145126

  14. "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…

  15. 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…

  16. 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

  17. 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…

  18. 36 CFR 7.63 - Dinosaur National Monument.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 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)...

  19. "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 and Fossils"; (4) "How Big…

  20. 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…

  1. 36 CFR 7.63 - Dinosaur National Monument.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 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)...

  2. 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)...

  3. 36 CFR 7.63 - Dinosaur National Monument.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 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)...

  4. Young Scientists Explore Dinosaurs. Book 8 Primary Level.

    ERIC Educational Resources Information Center

    Penn, Linda

    Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. Activities that focus on the dinosaur are organized into five sections. These include: (1) "Dinosaur Facts/Then and Now" (exploring bird and…

  5. 36 CFR 7.63 - Dinosaur National Monument.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 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)...

  6. Young Scientists Explore Dinosaurs. Book 8 Primary Level.

    ERIC Educational Resources Information Center

    Penn, Linda

    Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. Activities that focus on the dinosaur are organized into five sections. These include: (1) "Dinosaur Facts/Then and Now" (exploring bird and

  7. 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

  8. Effects of TGF-β1 and alginate on the differentiation of rabbit bone marrow-derived mesenchymal stem cells into a chondrocyte cell lineage

    PubMed Central

    WANG, WAN-ZONG; YAO, XIAO-DONG; HUANG, XIAO-JIN; LI, JIN-QUAN; XU, HAO

    2015-01-01

    The aim of the present study was to investigate the effect of a three-dimensional (3D) culture system of sodium alginate gel on the directional differentiation induction of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes, as well as the in vitro gene transfection technique. The biological characteristics of the passage and proliferation of rabbit BMSCs were investigated under conditions of in vitro monolayer and 3D culture of sodium alginate gel. Transforming growth factor (TGF)-β1 gene recombinant adenoviral cosmid vectors and the recombinant adenoviral vector Ad.TGF-β1 were constructed, and the effect of Ad.TGF-β1 transfection on the differentiation of BMSCs into chondrocytes was investigated. The whole bone marrow rinsing method was used to obtain, separate and purify the rabbit BMSCs, and the in vitro monolayer and 3D culture of sodium alginate gel were thus successfully and stably established. A safe, stable and efficient method of constructing Ad.TGF-β1 TGF-β1 gene recombinant adenoviral vectors was established. Following TGF-β1 transfection, BMSCs were able to continuously secrete significantly increased amounts of specific extracellular matrix components of chondrocytes, such as collagen II and proteoglycans. Furthermore, the effects in the post-gene transfection 3D culture group were found to be enhanced compared with those in the monolayer culture group. In conclusion, the 3D culture system of sodium alginate gel and in vitro gene transfection exhibited significant inductive effects on differentiation, which could be used to promote BMSCs to differentiate into chondrocytes. PMID:26622428

  9. The oldest dinosaur? A Middle Triassic dinosauriform from Tanzania

    PubMed Central

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

    2013-01-01

    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. PMID:23221875

  10. 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

    ... Service, Dinosaur National Monument, Dinosaur, CO AGENCY: National Park Service, Interior. ACTION: Notice. SUMMARY: The U.S. Department of the Interior, National Park Service, Dinosaur National Monument, Dinosaur... culturally affiliated with the human remains may contact Dinosaur National Monument. Disposition of the...

  11. 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 ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischian-bird functional convergence. PMID:22211275

  12. 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 ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischianbird functional convergence. PMID:22211275

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

    PubMed

    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

  14. 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

  15. 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

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

    PubMed Central

    Maidment, Susannah C. R.; Barrett, Paul M.

    2012-01-01

    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. PMID:22719033

  17. A late-surviving basal theropod dinosaur from the latest Triassic of North America

    PubMed Central

    Sues, Hans-Dieter; Nesbitt, Sterling J.; Berman, David S; Henrici, Amy C.

    2011-01-01

    The oldest theropod dinosaurs are known from the Carnian of Argentina and Brazil. However, the evolutionary diversification of this group after its initial radiation but prior to the Triassic–Jurassic boundary is still poorly understood because of a sparse fossil record near that boundary. Here, we report on a new basal theropod, Daemonosaurus chauliodus gen. et sp. nov., from the latest Triassic ‘siltstone member’ of the Chinle Formation of the Coelophysis Quarry at Ghost Ranch, New Mexico. Based on a comprehensive phylogenetic analysis, Daemonosaurus is more closely related to coeval neotheropods (e.g. Coelophysis bauri) than to Herrerasauridae and Eoraptor. The skeletal structure of Daemonosaurus and the recently discovered Tawa bridge a morphological gap between Eoraptor and Herrerasauridae on one hand and neotheropods on the other, providing additional support for the theropod affinities of both Eoraptor and Herrerasauridae and demonstrating that lineages from the initial radiation of Dinosauria persisted until the end of the Triassic. Various features of the skull of Daemonosaurus, including the procumbent dentary and premaxillary teeth and greatly enlarged premaxillary and anterior maxillary teeth, clearly set this taxon apart from coeval neotheropods and demonstrate unexpected disparity in cranial shape among theropod dinosaurs just prior to the end of the Triassic. PMID:21490016

  18. A late-surviving basal theropod dinosaur from the latest Triassic of North America.

    PubMed

    Sues, Hans-Dieter; Nesbitt, Sterling J; Berman, David S; Henrici, Amy C

    2011-11-22

    The oldest theropod dinosaurs are known from the Carnian of Argentina and Brazil. However, the evolutionary diversification of this group after its initial radiation but prior to the Triassic-Jurassic boundary is still poorly understood because of a sparse fossil record near that boundary. Here, we report on a new basal theropod, Daemonosaurus chauliodus gen. et sp. nov., from the latest Triassic 'siltstone member' of the Chinle Formation of the Coelophysis Quarry at Ghost Ranch, New Mexico. Based on a comprehensive phylogenetic analysis, Daemonosaurus is more closely related to coeval neotheropods (e.g. Coelophysis bauri) than to Herrerasauridae and Eoraptor. The skeletal structure of Daemonosaurus and the recently discovered Tawa bridge a morphological gap between Eoraptor and Herrerasauridae on one hand and neotheropods on the other, providing additional support for the theropod affinities of both Eoraptor and Herrerasauridae and demonstrating that lineages from the initial radiation of Dinosauria persisted until the end of the Triassic. Various features of the skull of Daemonosaurus, including the procumbent dentary and premaxillary teeth and greatly enlarged premaxillary and anterior maxillary teeth, clearly set this taxon apart from coeval neotheropods and demonstrate unexpected disparity in cranial shape among theropod dinosaurs just prior to the end of the Triassic. PMID:21490016

  19. 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. PMID:24802950

  20. A palaeoequatorial ornithischian and new constraints on early dinosaur diversification

    PubMed Central

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

    2014-01-01

    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. PMID:25100698

  1. Avian-like breathing mechanics in maniraptoran dinosaurs.

    PubMed

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

    2008-01-22

    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

  2. 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. PMID:25100698

  3. Fossilized excreta associated to dinosaurs in Brazil

    NASA Astrophysics Data System (ADS)

    Souto, P. R. F.; Fernandes, M. A.

    2015-01-01

    This work provides an updated register of the main occurrences of fossilized excreta (coprolites and urolites) associated with dinosaurs found in the Brazil. The goal is to provide a relevant guide to the interpretation of the environment in the context of Gondwana. In four geographic areas, the excreta are recovered from Cretaceous sedimentary deposits in outcrops of the Bauru and São Luis basins and the Upper Jurassic aeolian deposits of the Parana Basin in the state of São Paulo. The coprolites were analyzed by X-ray diffraction and X-ray fluorescence methods. The results of these analyses reveal compositions that differ from the surrounding matrix, indicating a partial substitution of the organic material due to the feeding habits of the producers. Additionally, we describe the urolite excavations in epirelief and hyporelief, the result of gravitational flow the impact from urine jets on sand. These are associated with ornithopod and theropod dinosaur footprints preserved in the aeolian flagstones of the Botucatu Formation, Parana Basin.

  4. Phylogenetic lineages in Entomophthoromycota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Entomophthoromycota Humber is one of five major phylogenetic lineages among the former phylum Zygomycota. These early terrestrial fungi share evolutionarily ancestral characters such as coenocytic mycelium and gametangiogamy as a sexual process resulting in zygospore formation. Previous molecular st...

  5. Myocardial Lineage Development

    PubMed Central

    Evans, Sylvia M.; Yelon, Deborah; Conlon, Frank L.; Kirby, Margaret L.

    2010-01-01

    The myocardium of the heart is composed of multiple highly specialized myocardial lineages, including those of the ventricular and atrial myocardium, and the specialized conduction system. Specification and maturation of each of these lineages during heart development is a highly ordered, ongoing process involving multiple signaling pathways and their intersection with transcriptional regulatory networks. Here, we attempt to summarize and compare much of what we know about specification and maturation of myocardial lineages from studies in several different vertebrate model systems. To date, most research has focused on early specification, and while there is still more to learn, less is known about factors that promote subsequent maturation of myocardial lineages required to build the functioning adult heart. PMID:21148449

  6. A troodontid dinosaur from the latest Cretaceous of India.

    PubMed

    Goswami, A; Prasad, G V R; Verma, O; Flynn, J J; Benson, R B J

    2013-01-01

    Troodontid dinosaurs share a close ancestry with birds and were distributed widely across Laurasia during the Cretaceous. Hundreds of occurrences of troodontid bones, and their highly distinctive teeth, are known from North America, Europe and Asia. Thus far, however, they remain unknown from Gondwanan landmasses. Here we report the discovery of a troodontid tooth from the uppermost Cretaceous Kallamedu Formation in the Cauvery Basin of South India. This is the first Gondwanan record for troodontids, extending their geographic range by nearly 10,000 km, and representing the first confirmed non-avian tetanuran dinosaur from the Indian subcontinent. This small-bodied maniraptoran dinosaur is an unexpected and distinctly 'Laurasian' component of an otherwise typical 'Gondwanan' tetrapod assemblage, including notosuchian crocodiles, abelisauroid dinosaurs and gondwanathere mammals. This discovery raises the question of whether troodontids dispersed to India from Laurasia in the Late Cretaceous, or whether a broader Gondwanan distribution of troodontids remains to be discovered. PMID:23591870

  7. 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. PMID:26023132

  8. Fossil Footprints: How Fast Was That Dinosaur Moving?

    ERIC Educational Resources Information Center

    Caton, Randall; Otts, Charlotte

    1999-01-01

    Describes an activity in which students construct relationships between their leg lengths, stride lengths, and movements in order to estimate the speeds of the dinosaurs that made various fossilized tracks. (WRM)

  9. A new carnivorous dinosaur from the Late Jurassic Solnhofen archipelago.

    PubMed

    Göhlich, Ursula B; Chiappe, Luis M

    2006-03-16

    Small Late Jurassic theropod dinosaurs are rare worldwide. In Europe these carnivorous dinosaurs are represented primarily by only two skeletons of Compsognathus, neither of which is well preserved. Here we describe a small new theropod dinosaur from the Late Jurassic period of Schamhaupten in southern Germany. Being exquisitely preserved and complete from the snout to the distal third of the tail, the new fossil is the best-preserved predatory, non-avian dinosaur in Europe. It possesses a suite of characters that support its identification as a basal coelurosaur. A cladistic analysis indicates that the new taxon is closer to maniraptorans than to tyrannosauroids, grouping it with taxa often considered to be compsognathids. Large portions of integument are preserved along its tail. The absence of feathers or feather-like structures in a fossil phylogenetically nested within feathered theropods indicates that the evolution of these integumentary structures might be more complex than previously thought. PMID:16541071

  10. An Interdisciplinary Approach to Dinosaur Fossils, Morphology, Ethology, and Energetics.

    ERIC Educational Resources Information Center

    Zipko, Stephen J.

    1981-01-01

    Describes an interdisciplinary minicourse on dinosaur fossils, morphology, ethology, and energetics. Suggests and provides examples of hands-on activities for junior high school- through college-level students. (DS)

  11. 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)

  12. Dinosaur extinction: closing the ‘3 m gap’

    PubMed Central

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

    2011-01-01

    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. PMID:21752814

  13. Heme compounds in dinosaur trabecular bone

    PubMed Central

    Schweitzer, Mary H.; Marshall, Mark; Carron, Keith; Bohle, D. Scott; Busse, Scott C.; Arnold, Ernst V.; Barnard, Darlene; Horner, J. R.; Starkey, Jean R.

    1997-01-01

    Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence of a paramagnetic compound consistent with heme. In addition, UV/visible spectroscopy and high performance liquid chromatography data are consistent with the Soret absorbance characteristic of this molecule. Resonance Raman profiles are also consistent with a modified heme structure. Finally, when dinosaurian tissues were extracted for protein fragments and were used to immunize rats, the resulting antisera reacted positively with purified avian and mammalian hemoglobins. The most parsimonious explanation of this evidence is the presence of blood-derived hemoglobin compounds preserved in the dinosaurian tissues. PMID:9177210

  14. Semiaquatic adaptations in a giant predatory dinosaur.

    PubMed

    Ibrahim, Nizar; Sereno, Paul C; Dal Sasso, Cristiano; Maganuco, Simone; Fabbri, Matteo; Martill, David M; Zouhri, Samir; Myhrvold, Nathan; Iurino, Dawid A

    2014-09-26

    We describe adaptations for a semiaquatic lifestyle in the dinosaur Spinosaurus aegyptiacus. These adaptations include retraction of the fleshy nostrils to a position near the mid-region of the skull and an elongate neck and trunk that shift the center of body mass anterior to the knee joint. Unlike terrestrial theropods, the pelvic girdle is downsized, the hindlimbs are short, and all of the limb bones are solid without an open medullary cavity, for buoyancy control in water. The short, robust femur with hypertrophied flexor attachment and the low, flat-bottomed pedal claws are consistent with aquatic foot-propelled locomotion. Surface striations and bone microstructure suggest that the dorsal "sail" may have been enveloped in skin that functioned primarily for display on land and in water. PMID:25213375

  15. The first ceratopsian dinosaur from South Korea.

    PubMed

    Lee, Yuong-Nam; Ryan, Michael J; Kobayashi, Yoshitsugu

    2011-01-01

    In 2008, a new basal neoceratopsian was discovered in the Tando beds (Albian) of Tando Basin in South Korea. It represents the first ceratopsian dinosaur in the Korean peninsula and is assigned to Koreaceratops hwaseongensis gen. et sp. nov. Autapomorphies of Koreaceratops include very tall neural spines over five times higher than the associated centra in the distal caudals, and a unique astragalus divided into two fossae by a prominent craniocaudal ridge on the proximal surface. A phylogenetic analysis indicates that Koreaceratops is positioned between Archaeoceratops and all more derived neoceratopsians, and the elongation of caudal neural spines was an important derived character in non-ceratopsid neoceratopsians. The very tall caudal neural spines in Koreaceratops, Montanoceratops, Udanoceratops, Protoceratops, and Bagaceratops appear to be homoplasious, suggesting an independent adaptation, possibly for swimming. Skeletal evidence suggests that obligate quadrupedalism occurred gradually in neoceratopsians progressing from bipedal through facultative quadrupedalism, to complete quadrupedalism in Coronosauria. PMID:21085924

  16. The first ceratopsian dinosaur from South Korea

    NASA Astrophysics Data System (ADS)

    Lee, Yuong-Nam; Ryan, Michael J.; Kobayashi, Yoshitsugu

    2011-01-01

    In 2008, a new basal neoceratopsian was discovered in the Tando beds (Albian) of Tando Basin in South Korea. It represents the first ceratopsian dinosaur in the Korean peninsula and is assigned to Koreaceratops hwaseongensis gen. et sp. nov. Autapomorphies of Koreaceratops include very tall neural spines over five times higher than the associated centra in the distal caudals, and a unique astragalus divided into two fossae by a prominent craniocaudal ridge on the proximal surface. A phylogenetic analysis indicates that Koreaceratops is positioned between Archaeoceratops and all more derived neoceratopsians, and the elongation of caudal neural spines was an important derived character in non-ceratopsid neoceratopsians. The very tall caudal neural spines in Koreaceratops, Montanoceratops, Udanoceratops, Protoceratops, and Bagaceratops appear to be homoplasious, suggesting an independent adaptation, possibly for swimming. Skeletal evidence suggests that obligate quadrupedalism occurred gradually in neoceratopsians progressing from bipedal through facultative quadrupedalism, to complete quadrupedalism in Coronosauria.

  17. Introgression of mitochondrial DNA among lineages in a hybridogenetic ant

    PubMed Central

    Darras, Hugo; Aron, Serge

    2015-01-01

    We report a remarkable pattern of incongruence between nuclear and mitochondrial variations in a social insect, the desert ant Cataglyphis hispanica. This species reproduces by social hybridogenesis. In all populations, two distinct genetic lineages coexist; non-reproductive workers develop from hybrid crosses between the lineages, whereas reproductive offspring (males and new queens) are typically produced asexually by parthenogenesis. Genetic analyses based on nuclear markers revealed that the two lineages remain highly differentiated despite constant hybridization for worker production. Here, we show that, in contrast with nuclear DNA, mitochondrial DNA (mtDNA) does not recover the two lineages as monophyletic. Rather, mitochondrial haplotypes cluster according to their geographical origin. We argue that this cytonuclear incongruence stems from introgression of mtDNA among lineages, and review the mechanisms likely to explain this pattern under social hybridogenesis. PMID:25652221

  18. Stem cell differentiation: Sticky mechanical memory

    NASA Astrophysics Data System (ADS)

    Eyckmans, Jeroen; Chen, Christopher S.

    2014-06-01

    Physical cues from the extracellular environment influence the lineage commitment of stem cells. Now, experiments on human mesenchymal stem cells cultured on photodegradable hydrogels show that the cells' fate can also be determined by past physical environments.

  19. Ectoderm to mesoderm lineage switching during axolotl tail regeneration.

    PubMed

    Echeverri, Karen; Tanaka, Elly M

    2002-12-01

    Foreign environments may induce adult stem cells to switch lineages and populate multiple tissue types, but whether this mechanism is used for tissue repair remains uncertain. Urodele amphibians can regenerate fully functional, multitissue structures including the limb and tail. To determine whether lineage switching is an integral feature of this regeneration, we followed individual spinal cord cells live during tail regeneration in the axolotl. Spinal cord cells frequently migrate into surrounding tissue to form regenerating muscle and cartilage. Thus, in axolotls, cells switch lineage during a real example of regeneration. PMID:12471259

  20. Normal and leukemic stem cells

    PubMed Central

    Pelicci, P G

    2012-01-01

    Studies on hematopoietic stem cells have provided several critical insights in the biology of stem cells in general; as mature blood cells are generally short lived, stem cells are in fact required to guarantee, throughout the life of an organism, the replenishment of differentiated blood cells by the generation of multi-lineage progenitors and precursors committed to individual hematopoietic lineages. Similarly, acute myeloid leukemia has been considered as a model system to study cancer stem cells. This presentation illustrates some recent results obtained by our group with regard to both normal and leukemic stem cells.

  1. 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

  2. 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…

  3. 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 the origin of birds and cannot be explained as an adaptation for flight. We hypothesise that skeletal density modulation in small, non-volant, maniraptorans resulted in energetic savings as part of a multi-system response to increased metabolic demands. Acquisition of extensive postcranial pneumaticity in small-bodied maniraptorans may indicate avian-like high-performance endothermy. PMID:21733078

  4. Phylogenetic lineages in Entomophthoromycota.

    PubMed

    Gryganskyi, A P; Humber, R A; Smith, M E; Hodge, K; Huang, B; Voigt, K; Vilgalys, R

    2013-06-01

    Entomophthoromycota is one of six major phylogenetic lineages among the former phylum Zygomycota. These early terrestrial fungi share evolutionarily ancestral characters such as coenocytic mycelium and gametangiogamy as a sexual process resulting in zygospore formation. Previous molecular studies have shown the monophyly of Entomophthoromycota, thus justifying raising the taxonomic status of these fungi to a phylum. Multi-gene phylogenies have identified five major lineages of Entomophthoromycota. In this review we provide a detailed discussion about the biology and taxonomy of these lineages: I) Basidiobolus (Basidiobolomycetes: Basidiobolaceae; primarily saprobic); II) Conidiobolus (Entomophthoromycetes, Ancylistaceae; several clades of saprobes and invertebrate pathogens), as well as three rapidly evolving entomopathogenic lineages in the family Entomophthoraceae centering around; III) Batkoa; IV) Entomophthora and allied genera; and V) the subfamily Erynioideae which includes Zoophthora and allied genera. Molecular phylogenic analysis has recently determined the relationships of several taxa that were previously unresolved based on morphology alone: Eryniopsis, Macrobiotophthora, Massospora, Strongwellsea and two as yet undescribed genera of Basidiobolaceae. PMID:24027349

  5. 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

  6. 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. PMID:20107440

  7. Thoracic epaxial muscles in living archosaurs and ornithopod dinosaurs.

    PubMed

    Organ, Christopher Lee

    2006-07-01

    Crocodylians possess the same thoracic epaxial muscles as most other saurians, but M. transversospinalis is modified by overlying osteoderms. Compared with crocodylians, the thoracic epaxial muscles of birds are reduced in size, disrupted by the synsacrum, and often modified by intratendinous ossification and the notarium. A phylogenetic perspective is used to determine muscle homologies in living archosaurs (birds and crocodylians), evaluate how the apparent disparity evolved, and reconstruct the thoracic epaxial muscles in ornithopod dinosaurs. The avian modifications of the epaxial musculoskeletal system appear to have coevolved with the synsacrum and notarium. The lattice of ossified tendons in iguanodontoidean dinosaurs (Hadrosauridae and Iguanodontidae) is homologized to M. transversospinalis in crocodylians and M. longus colli dorsalis, pars thoracica in birds. Birds have an arrangement of tendons within M. longus colli dorsalis, pars thoracica identical to that observed in the epaxial ossified tendons of iguanodontoid dinosaurs. Moreover, many birds (such as grebes and turkeys) ossify these tendons, resulting in a two- or three-layered lattice of ossified tendons, a morphology also seen in iguanodontoid dinosaurs. Although the structure of M. transversospinalis appears indistinguishable between birds and iguanodontoid dinosaurs, intratendinous ossification within this epaxial muscle evolved convergently. PMID:16779820

  8. 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.

  9. 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

  10. Neuroblast lineage identification and lineage-specific Hox gene action during postembryonic development of the subesophageal ganglion in the Drosophila central brain.

    PubMed

    Kuert, Philipp A; Hartenstein, Volker; Bello, Bruno C; Lovick, Jennifer K; Reichert, Heinrich

    2014-06-15

    The central brain of Drosophila consists of the supraesophageal ganglion (SPG) and the subesophageal ganglion (SEG), both of which are generated by neural stem cell-like neuroblasts during embryonic and postembryonic development. Considerable information has been obtained on postembryonic development of the neuroblasts and their lineages in the SPG. In contrast, very little is known about neuroblasts, neural lineages, or any other aspect of the postembryonic development in the SEG. Here we characterize the neuroanatomy of the larval SEG in terms of tracts, commissures, and other landmark features as compared to a thoracic ganglion. We then use clonal MARCM labeling to identify all adult-specific neuroblast lineages in the late larval SEG and find a surprisingly small number of neuroblast lineages, 13 paired and one unpaired. The Hox genes Dfd, Scr, and Antp are expressed in a lineage-specific manner in these lineages during postembryonic development. Hox gene loss-of-function causes lineage-specific defects in axonal targeting and reduction in neural cell numbers. Moreover, it results in the formation of novel ectopic neuroblast lineages. Apoptosis block also results in ectopic lineages suggesting that Hox genes are required for lineage-specific termination of proliferation through programmed cell death. Taken together, our findings show that postembryonic development in the SEG is mediated by a surprisingly small set of identified lineages and requires lineage-specific Hox gene action to ensure the correct formation of adult-specific neurons in the Drosophila brain. PMID:24713419

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

    NASA Astrophysics Data System (ADS)

    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.

  12. 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. PMID:27112293

  13. Putative intestinal stem cells

    PubMed Central

    Pirvulet, V

    2015-01-01

    A heterogeneous set of intestinal stem cells markers has been described in intestinal glands but the ultrastructural identity of intestinal stem cells remains unknown. By using electron microscopy, this study demonstrated the presence of cells with stem morphology in the intestinal glands of mice of different ages. These putative intestinal stem cells have large, euchromatic, irregular shaped nucleus, large, visible nucleolus, few ER cisternae and mitochondria. Their morphology is distinct from the morphology of any other intestinal gland cell. Stem cells located at the base of intestinal glands undergo mitosis. This study enhances the hypothesis of a gland (crypt) base columnar cell that gives rise to all the intestinal lineages. PMID:26366225

  14. Launching the T-Lineage Developmental Programme

    PubMed Central

    Rothenberg, Ellen V.; Moore, Jonathan E.; Yui, Mary A.

    2011-01-01

    Preface Multipotent blood progenitor cells enter the thymus and begin a protracted differentiation process in which they gradually acquire T-cell characteristics while shedding their legacy of developmental plasticity. Notch signalling and basic helix-loop-helix E-protein transcription factors collaborate repeatedly to trigger and sustain this process throughout the period leading up to T-cell lineage commitment. Nevertheless, the process is discontinuous with separately regulated steps that demand roles for additional collaborating factors. This review discusses new evidence on the coordination of specification and commitment in the early T-cell pathway; effects of microenvironmental signals; the inheritance of stem-cell regulatory factors; and the ensemble of transcription factors that modulate the effects of Notch and E proteins, to distinguish individual stages and to polarize T-lineage fate determination. PMID:18097446

  15. 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

  16. 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. PMID:25993090

  17. 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. PMID:24105904

  18. 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.

  19. 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

  20. 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.

  1. Bird embryos uncover homology and evolution of the dinosaur ankle.

    PubMed

    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

  2. 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.

  3. Estimating cranial musculoskeletal constraints in theropod dinosaurs

    PubMed Central

    Lautenschlager, Stephan

    2015-01-01

    Many inferences on the biology, behaviour and ecology of extinct vertebrates are based on the reconstruction of the musculature and rely considerably on its accuracy. Although the advent of digital reconstruction techniques has facilitated the creation and testing of musculoskeletal hypotheses in recent years, muscle strain capabilities have rarely been considered. Here, a digital modelling approach using the freely available visualization and animation software Blender is applied to estimate cranial muscle length changes and optimal and maximal possible gape in different theropod dinosaurs. Models of living archosaur taxa (Alligator mississippiensis, Buteo buteo) were used in an extant phylogenetically bracketed framework to validate the method. Results of this study demonstrate that Tyrannosaurus rex, Allosaurus fragilis and Erlikosaurus andrewsi show distinct differences in the recruitment of the jaw adductor musculature and resulting gape, confirming previous dietary and ecological assumptions. While the carnivorous taxa T. rex and Allo. fragilis were capable of a wide gape and sustained muscle force, the herbivorous therizinosaurian E. andrewsi was constrained to small gape angles. PMID:26716007

  4. Estimating cranial musculoskeletal constraints in theropod dinosaurs.

    PubMed

    Lautenschlager, Stephan

    2015-11-01

    Many inferences on the biology, behaviour and ecology of extinct vertebrates are based on the reconstruction of the musculature and rely considerably on its accuracy. Although the advent of digital reconstruction techniques has facilitated the creation and testing of musculoskeletal hypotheses in recent years, muscle strain capabilities have rarely been considered. Here, a digital modelling approach using the freely available visualization and animation software Blender is applied to estimate cranial muscle length changes and optimal and maximal possible gape in different theropod dinosaurs. Models of living archosaur taxa (Alligator mississippiensis, Buteo buteo) were used in an extant phylogenetically bracketed framework to validate the method. Results of this study demonstrate that Tyrannosaurus rex, Allosaurus fragilis and Erlikosaurus andrewsi show distinct differences in the recruitment of the jaw adductor musculature and resulting gape, confirming previous dietary and ecological assumptions. While the carnivorous taxa T. rex and Allo. fragilis were capable of a wide gape and sustained muscle force, the herbivorous therizinosaurian E. andrewsi was constrained to small gape angles. PMID:26716007

  5. Global aspects of dinosaur distribution and evolution

    SciTech Connect

    Sues, H.

    1988-02-01

    Late Jurassic dinosaurian assemblages show close taxonomic correspondence over wide geographical ranges. Presently available if meager evidence suggests that this is also the case for Early Cretaceous communities. Cretaceous dinosaurian assemblages of Campanian and Maastrichtian age show considerable geographical differentiation but also some wide-ranging genera. Northern Hemisphere terrestrial ecosystems were dominated by hadrosaurs and ceratopsians, both herbivores with advanced capabilities for oral food-processing, whereas Southern Hemisphere biota were characterized by the abundance of titanosaurid sauropods, which relied on gut processing. Very close taxonomic similarities exist between the Campanian and early Maastrichtian dinosaurian assemblages of Mongolia and western North America, which, in part, is matched by similarities among other tetrapods such as mammals. Endemic dinosaurs in the Southern Hemisphere appear to reflect major changes in continental configuration. Some evidence exists for interchange of fuanal elements between North and South America. In absence of late Maastrichtian dinosaurian assemblages from most regions, scenarios concerning the terminal Cretaceous extinction of the Dinosauria should be regarded with caution because they are exclusively based on the conditions in western North America.

  6. 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. PMID:19793755

  7. 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

  8. 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. PMID:15888409

  9. 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

  10. 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.

  11. 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 ecosystem convergence. The proportion of different ecomorphs, which reflects the prevailing climatic and environmental conditions present during fossil deposition, may therefore be used to differentiate Late Jurassic dinosaur fossil assemblages. This method is broadly applicable to different taxa and times, allowing one to address questions of evolutionary, biogeographic, and climatic importance. PMID:20838442

  12. Primed and ready: understanding lineage commitment through single cell analysis.

    PubMed

    Nimmo, Rachael A; May, Gillian E; Enver, Tariq

    2015-08-01

    Regulation of lineage commitment in multipotential cells is key to maintaining a balanced hematopoietic output throughout life while retaining the capacity to respond to stress and infection. Cell fate decisions are made by individual stem cells, but population-level analysis obscures the mechanics of cell fate choice by averaging the molecular and functional heterogeneity that exists even in the most highly purified stem cell populations. Therefore, single cell analysis of both molecular and cellular phenotypes is crucial to delineate and interrogate the process of lineage commitment. We review recent single cell expression profiling, imaging, and clonal tracking studies that have provided new insights into commitment, focusing on the hematopoietic system, and suggest how new technologies may illuminate our understanding of lineage commitment in the near future. PMID:26004869

  13. Structural Extremes in a Cretaceous Dinosaur

    PubMed Central

    Sereno, Paul C.; Wilson, Jeffrey A.; Witmer, Lawrence M.; Whitlock, John A.; Maga, Abdoulaye; Ide, Oumarou; Rowe, Timothy A.

    2007-01-01

    Fossils of the Early Cretaceous dinosaur, Nigersaurus taqueti, document for the first time the cranial anatomy of a rebbachisaurid sauropod. Its extreme adaptations for herbivory at ground-level challenge current hypotheses regarding feeding function and feeding strategy among diplodocoids, the larger clade of sauropods that includes Nigersaurus. We used high resolution computed tomography, stereolithography, and standard molding and casting techniques to reassemble the extremely fragile skull. Computed tomography also allowed us to render the first endocast for a sauropod preserving portions of the olfactory bulbs, cerebrum and inner ear, the latter permitting us to establish habitual head posture. To elucidate evidence of tooth wear and tooth replacement rate, we used photographic-casting techniques and crown thin sections, respectively. To reconstruct its 9-meter postcranial skeleton, we combined and size-adjusted multiple partial skeletons. Finally, we used maximum parsimony algorithms on character data to obtain the best estimate of phylogenetic relationships among diplodocoid sauropods. Nigersaurus taqueti shows extreme adaptations for a dinosaurian herbivore including a skull of extremely light construction, tooth batteries located at the distal end of the jaws, tooth replacement as fast as one per month, an expanded muzzle that faces directly toward the ground, and hollow presacral vertebral centra with more air sac space than bone by volume. A cranial endocast provides the first reasonably complete view of a sauropod brain including its small olfactory bulbs and cerebrum. Skeletal and dental evidence suggests that Nigersaurus was a ground-level herbivore that gathered and sliced relatively soft vegetation, the culmination of a low-browsing feeding strategy first established among diplodocoids during the Jurassic. PMID:18030355

  14. Structural extremes in a cretaceous dinosaur.

    PubMed

    Sereno, Paul C; Wilson, Jeffrey A; Witmer, Lawrence M; Whitlock, John A; Maga, Abdoulaye; Ide, Oumarou; Rowe, Timothy A

    2007-01-01

    Fossils of the Early Cretaceous dinosaur, Nigersaurus taqueti, document for the first time the cranial anatomy of a rebbachisaurid sauropod. Its extreme adaptations for herbivory at ground-level challenge current hypotheses regarding feeding function and feeding strategy among diplodocoids, the larger clade of sauropods that includes Nigersaurus. We used high resolution computed tomography, stereolithography, and standard molding and casting techniques to reassemble the extremely fragile skull. Computed tomography also allowed us to render the first endocast for a sauropod preserving portions of the olfactory bulbs, cerebrum and inner ear, the latter permitting us to establish habitual head posture. To elucidate evidence of tooth wear and tooth replacement rate, we used photographic-casting techniques and crown thin sections, respectively. To reconstruct its 9-meter postcranial skeleton, we combined and size-adjusted multiple partial skeletons. Finally, we used maximum parsimony algorithms on character data to obtain the best estimate of phylogenetic relationships among diplodocoid sauropods. Nigersaurus taqueti shows extreme adaptations for a dinosaurian herbivore including a skull of extremely light construction, tooth batteries located at the distal end of the jaws, tooth replacement as fast as one per month, an expanded muzzle that faces directly toward the ground, and hollow presacral vertebral centra with more air sac space than bone by volume. A cranial endocast provides the first reasonably complete view of a sauropod brain including its small olfactory bulbs and cerebrum. Skeletal and dental evidence suggests that Nigersaurus was a ground-level herbivore that gathered and sliced relatively soft vegetation, the culmination of a low-browsing feeding strategy first established among diplodocoids during the Jurassic. PMID:18030355

  15. Instruction of hematopoietic lineage choice by cytokine signaling

    SciTech Connect

    Endele, Max; Etzrodt, Martin; Schroeder, Timm

    2014-12-10

    Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support the production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.

  16. 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

  17. 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

  18. [Post-microtraumatic cervical osteoarthritis in a cretaceus dinosaur].

    PubMed

    D'Anastasio, R; Capasso, L

    2004-01-01

    The authors describe a very rare case of osteoarthritis in a cervical vertebra of a cretaceous dinosaur (Spinosaurus maroccanus). Besides it is one of the most ancient case of osteoarthritis published up today. The fossil record was studied through macroscopic and radiographic analyses and computed tomography scan. PMID:15309222

  19. 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…

  20. Fossils and Dinosaurs--A Fully Integrated Instructional Unit.

    ERIC Educational Resources Information Center

    Kuehl, Matt; And Others

    This lesson plan for the second and third grades uses information on dinosaurs, their adaptations and survival, to provide science education for limited-English-proficient (LEP) students in San Diego, California. The primary text is "Los Dinosaurios Gigantes," a core literature book used in the school district. Lessons are based on the whole

  1. Evolutionary genomics: a dinosaur's view of genome-size evolution.

    PubMed

    Ellegren, Hans

    2007-06-19

    Estimates of cell volume in fossilized bones of extinct dinosaurs indicate that genome size underwent a significant reduction in the early theropods, from which birds later evolved. This suggests that birds' small genomes are not an adaptation to metabolic demands associated with flight. PMID:17580079

  2. Paleontology: a cock's comb on a duck-billed dinosaur.

    PubMed

    Horner, John R

    2014-01-20

    A soft tissue structure has been discovered on the head of the duck-billed dinosaur Edmontosaurus. Its similarity to a cock's comb and other sexually dimorphic structures of birds suggests that potential sexual signals existed in these extinct animals. PMID:24456984

  3. Progenitor Epithelium: Sorting Out Pancreatic Lineages.

    PubMed

    Marty-Santos, Leilani; Cleaver, Ondine

    2015-08-01

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

  4. Lineage and clonal development of gastric glands.

    PubMed

    Nomura, S; Esumi, H; Job, C; Tan, S S

    1998-12-01

    Individual gastric glands of the stomach are composed of cells of different phenotypes. These are derived from multipotent progenitor stem cells located at the isthmus region of the gland. Previous cell lineage analyses suggest that gastric glands, as in the colon and small intestine, are invariably monoclonal by adult stages. However, little is known about the ontogenetic progression of glandular clonality in the stomach. To examine this issue, we employed an in situ cell lineage marker in female mice heterozygous for an X-linked transgene. We found that stomach glands commence development as polyclonal units, but by adulthood (6 weeks), the majority progressed to monoclonal units. Our analysis suggests that at least three progenitor cells are required to initiate the development of individual gastric glands if they are analyzed just after birth. Hence, unlike the colon and small intestine, stomachs showed a significant fraction (10-25%) of polyclonal glands at adult stages. We suggest that these glands persist from polyclonal glands present in the embryonic stomach and hypothesize that they represent a subpopulation of glands with larger numbers of self-renewing stem cells. PMID:9851847

  5. 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

  6. No evidence for directional evolution of body mass in herbivorous theropod dinosaurs.

    PubMed

    Zanno, Lindsay E; Makovicky, Peter J

    2013-01-22

    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

  7. 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. PMID:25228349

  8. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace

    USGS Publications Warehouse

    Milner, A.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.

  9. Rates of dinosaur limb evolution provide evidence for exceptional radiation in Mesozoic birds.

    PubMed

    Benson, Roger B J; Choiniere, Jonah N

    2013-10-01

    Birds are the most diverse living tetrapod group and are a model of large-scale adaptive radiation. Neontological studies suggest a radiation within the avian crown group, long after the origin of flight. However, deep time patterns of bird evolution remain obscure because only limited fossil data have been considered. We analyse cladogenesis and limb evolution on the entire tree of Mesozoic theropods, documenting the dinosaur-bird transition and immediate origins of powered flight. Mesozoic birds inherited constraints on forelimb evolution from non-flying ancestors, and species diversification rates did not accelerate in the earliest flying taxa. However, Early Cretaceous short-tailed birds exhibit both phenotypic release of the hindlimb and increased diversification rates, unparalleled in magnitude at any other time in the first 155 Myr of theropod evolution. Thus, a Cretaceous adaptive radiation of stem-group birds was enabled by restructuring of the terrestrial locomotor module, which represents a key innovation. Our results suggest two phases of radiation in Avialae: with the Cretaceous diversification overwritten by extinctions of stem-group birds at the Cretaceous-Palaeogene boundary, and subsequent diversification of the crown group. Our findings illustrate the importance of fossil data for understanding the macroevolutionary processes generating modern biodiversity. PMID:23945695

  10. 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 of angiosperm trees in ecological range through swamps and floodplains during the Late Cretaceous and subsequent change of herbivorous dinosaurs' dietary habit and the increase of volcanic activity in the Cretaceous. The other is related with the nesting behaviour in the Cretaceous. By contrast to the geochronologically restricted occurrence of dinosaur eggs, paleoenvironments of nesting areas of dinosaurs are varying from inland areas (alluvial fan, fluvial plain, desert, lake, etc.) to coastal areas (coastal plain, beach, lagoon), suggesting that dinosaurs avoided competition in sharing nesting areas. Little change in lithology from nested deposits to subsequent burying sediments indicates that dinosaurs preferred stable environment in terms of sedimentation as nesting sites. Key words: Dinosaur eggs, Cretaceous, Paleobiological occurrence, Korea

  11. Gradual dinosaur extinction and simultaneous ungulate radiation in the hell creek formation.

    PubMed

    Sloan, R E; Rigby, J K; VAN Valen, L M; Gabriel, D

    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. PMID:17781415

  12. 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.

  13. Nostril position in dinosaurs and other vertebrates and its significance for nasal function.

    PubMed

    Witmer, L M

    2001-08-01

    Many dinosaurs have enormous and complicated bony nasal apertures. Functional interpretation requires knowledge of the location of the external opening in the skin. Traditionally, the fleshy nostril of dinosaurs has been placed in the back of the bony opening, but studies of extant dinosaur relatives suggest that it is located far forward. Narial blood supply and cavernous tissue corroborate the rostral position in dinosaurs. A rostral nostril was, and remains, a virtually invariant rule of construction among Amniota, which has consequences for (i) nasal airstreaming, and hence various physiological parameters, and (ii) the collection of behaviorally relevant circumoral odorants. PMID:11486085

  14. A phylogenetic study of the section moduli of the humerus in bipedal theropod dinosaurs

    NASA Astrophysics Data System (ADS)

    Lee, Scott; Richards, Zachary

    The section modulus of a bone is a measure of its ability to resist bending torques. Carnivorous dinosaurs including Tyrannosauroidea and Allosauroidea had strong humeri, presumably to hold struggling prey during hunting. The herbivorous dinosaurs of Ornithomimosauria had weak arm bones. This is believed to reflect the fact that their arms were never subjected to large bending torques. The unusual dinosaurs of Therizinosauria had arms as strong as found in the carnivorous dinosaurs. This is consistent with the hypothesis that their manus suggests a digging lifestyle. Other groups including Oviraptorosauria, Troodontidae, Dromaeosauridae and Compsognathidae are also examined.

  15. Evidence for endothermic ancestors of crocodiles at the stem of archosaur evolution.

    PubMed

    Seymour, Roger S; Bennett-Stamper, Christina L; Johnston, Sonya D; Carrier, David R; Grigg, Gordon C

    2004-01-01

    Physiological, anatomical, and developmental features of the crocodilian heart support the paleontological evidence that the ancestors of living crocodilians were active and endothermic, but the lineage reverted to ectothermy when it invaded the aquatic, ambush predator niche. In endotherms, there is a functional nexus between high metabolic rates, high blood flow rates, and complete separation of high systemic blood pressure from low pulmonary blood pressure in a four-chambered heart. Ectotherms generally lack all of these characteristics, but crocodilians retain a four-chambered heart. However, crocodilians have a neurally controlled, pulmonary bypass shunt that is functional in diving. Shunting occurs outside of the heart and involves the left aortic arch that originates from the right ventricle, the foramen of Panizza between the left and right aortic arches, and the cog-tooth valve at the base of the pulmonary artery. Developmental studies show that all of these uniquely crocodilian features are secondarily derived, indicating a shift from the complete separation of blood flow of endotherms to the controlled shunting of ectotherms. We present other evidence for endothermy in stem archosaurs and suggest that some dinosaurs may have inherited the trait. PMID:15674775

  16. 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 poor sampling in the Turonian-Santonian interval. Stegosauria shows a significant negative correlation with flowering plants and a significant positive correlation with the nonflowering cycadophytes (cycads, Bennettitales). This interesting pattern is worthy of further investigation, and it reflects the decline of both stegosaurs and cycadophytes during the Early Cretaceous. PMID:19210589

  17. A gigantic feathered dinosaur from the lower cretaceous of China.

    PubMed

    Xu, Xing; Wang, Kebai; Zhang, Ke; Ma, Qingyu; Xing, Lida; Sullivan, Corwin; Hu, Dongyu; Cheng, Shuqing; Wang, Shuo

    2012-04-01

    Numerous feathered dinosaur specimens have recently been recovered from the Middle-Upper Jurassic and Lower Cretaceous deposits of northeastern China, but most of them represent small animals. Here we report the discovery of a gigantic new basal tyrannosauroid, Yutyrannus huali gen. et sp. nov., based on three nearly complete skeletons representing two distinct ontogenetic stages from the Lower Cretaceous Yixian Formation of Liaoning Province, China. Y. huali shares some features, particularly of the cranium, with derived tyrannosauroids, but is similar to other basal tyrannosauroids in possessing a three-fingered manus and a typical theropod pes. Morphometric analysis suggests that Y. huali differed from tyrannosaurids in its growth strategy. Most significantly, Y. huali bears long filamentous feathers, thus providing direct evidence for the presence of extensively feathered gigantic dinosaurs and offering new insights into early feather evolution. PMID:22481363

  18. An Abelisauroid Theropod Dinosaur from the Turonian of Madagascar

    PubMed Central

    Farke, Andrew A.; Sertich, Joseph J. W.

    2013-01-01

    Geophysical evidence strongly supports the complete isolation of India and Madagascar (Indo-Madagascar) by ∼100 million years ago, though sparse terrestrial fossil records from these regions prior to ∼70 million years ago have limited insights into their biogeographic history during the Cretaceous. A new theropod dinosaur, Dahalokely tokana, from Turonian-aged (∼90 million years old) strata of northernmost Madagascar is represented by a partial axial column. Autapomorphies include a prominently convex prezygoepipophyseal lamina on cervical vertebrae and a divided infraprezygapophyseal fossa through the mid-dorsal region, among others. Phylogenetic analysis definitively recovers the species as an abelisauroid theropod and weakly as a noasaurid. Dahalokely is the only known dinosaur from the interval during which Indo-Madagascar likely existed as a distinct landmass, but more complete material is needed to evaluate whether or not it is more closely related to later abelisauroids of Indo-Madagascar or those known elsewhere in Gondwana. PMID:23637961

  19. An Early Cretaceous heterodontosaurid dinosaur with filamentous integumentary structures.

    PubMed

    Zheng, Xiao-Ting; You, Hai-Lu; Xu, Xing; Dong, Zhi-Ming

    2009-03-19

    Ornithischia is one of the two major groups of dinosaurs, with heterodontosauridae as one of its major clades. Heterodontosauridae is characterized by small, gracile bodies and a problematic phylogenetic position. Recent phylogenetic work indicates that it represents the most basal group of all well-known ornithischians. Previous heterodontosaurid records are mainly from the Early Jurassic period (205-190 million years ago) of Africa. Here we report a new heterodontosaurid, Tianyulong confuciusi gen. et sp. nov., from the Early Cretaceous period (144-99 million years ago) of western Liaoning Province, China. Tianyulong extends the geographical distribution of heterodontosaurids to Asia and confirms the clade's previously questionable temporal range extension into the Early Cretaceous period. More surprisingly, Tianyulong bears long, singular and unbranched filamentous integumentary (outer skin) structures. This represents the first confirmed report, to our knowledge, of filamentous integumentary structures in an ornithischian dinosaur. PMID:19295609

  20. Extreme Cranial Ontogeny in the Upper Cretaceous Dinosaur Pachycephalosaurus

    PubMed Central

    Horner, John R.; Goodwin, Mark B.

    2009-01-01

    Background Extended neoteny and late stage allometric growth increase morphological disparity between growth stages in at least some dinosaurs. Coupled with relatively low dinosaur density in the Upper Cretaceous of North America, ontogenetic transformational representatives are often difficult to distinguish. For example, many hadrosaurids previously reported to represent relatively small lambeosaurine species were demonstrated to be juveniles of the larger taxa. Marginocephalians (pachycephalosaurids + ceratopsids) undergo comparable and extreme cranial morphological change during ontogeny. Methodology/Principal Findings Cranial histology, morphology and computer tomography reveal patterns of internal skull development that show the purported diagnostic characters for the pachycephalosaurids Dracorex hogwartsia and Stygimoloch spinifer are ontogenetically derived features. Coronal histological sections of the frontoparietal dome of an adult Pachycephalosaurus wyomingensis reveal a dense structure composed of metaplastic bone with a variety of extremely fibrous and acellular tissue. Coronal histological sections and computer tomography of a skull and frontoparietal dome of Stygimoloch spinifer reveal an open intrafrontal suture indicative of a subadult stage of development. These dinosaurs employed metaplasia to rapidly grow and change the size and shape of their horns, cranial ornaments and frontoparietal domes, resulting in extreme cranial alterations during late stages of growth. We propose that Dracorex hogwartsia, Stygimoloch spinifer and Pachycephalosaurus wyomingensis are the same taxon and represent an ontogenetic series united by shared morphology and increasing skull length. Conclusions/Significance Dracorex hogwartsia (juvenile) and Stygimoloch spinifer (subadult) are reinterpreted as younger growth stages of Pachycephalosaurus wyomingensis (adult). This synonymy reduces the number of pachycephalosaurid taxa from the Upper Cretaceous of North America and demonstrates the importance of cranial ontogeny in evaluating dinosaur diversity and taxonomy. These growth stages reflect a continuum rather than specific developmental steps defined by “known” terminal morphologies. PMID:19859556

  1. 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 limited by overheating impossible. PMID:24204568

  2. Observations on continuously growing roots of the sloth and the K14-Eda transgenic mice indicate that epithelial stem cells can give rise to both the ameloblast and root epithelium cell lineage creating distinct tooth patterns.

    PubMed

    Tummers, Mark; Thesleff, Irma

    2008-01-01

    Root development is traditionally associated with the formation of Hertwig's epithelial root sheath (HERS), whose fragments give rise to the epithelial cell rests of Malassez (ERM). The HERS is formed by depletion of the core of stellate reticulum cells, the putative stem cells, in the cervical loop, leaving only a double layer of the basal epithelium with limited growth capacity. The continuously growing incisor of the rodent is subdivided into a crown analog half on the labial side, with a cervical loop containing a large core of stellate reticulum, and its progeny gives rise to enamel producing. The lingual side is known as the root analog and gives rise to ERM. We show that the lingual cervical loop contains a small core of stellate reticulum cells and suggest that it acts as a functional stem cell niche. Similarly we show that continuously growing roots represented by the sloth molar and K14-Eda transgenic incisor maintain a cervical loop with a small core of stellate reticulum cells around the entire circumference of the tooth and do not form a HERS, and still give rise to ERM. We propose that HERS is not a necessary structure to initiate root formation. Moreover, we conclude that crown vs. root formation, i.e. the production of enamel vs. cementum, and the differentiation of the epithelial cells into ameloblasts vs. ERM, can be regulated independently from the regulation of stem cell maintenance. This developmental flexibility may underlie the developmental and evolutionary diversity in tooth patterning. PMID:18315812

  3. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  4. Low beta diversity of Maastrichtian dinosaurs of North America.

    PubMed

    Vavrek, Matthew J; Larsson, Hans C E

    2010-05-01

    Beta diversity is an important component of large-scale patterns of biodiversity, but its explicit examination is more difficult than that of alpha diversity. Only recently have data sets large enough been presented to begin assessing global patterns of species turnover, especially in the fossil record. We present here an analysis of beta diversity of a Maastrichtian (71-65 million years old) assemblage of dinosaurs from the Western Interior of North America, a region that covers approximately 1.5 x 10(6) km(2), borders an epicontinental sea, and spans approximately 20 degrees of latitude. Previous qualitative analyses have suggested regional groupings of these dinosaurs and generally concluded that there were multiple distinct faunal regions. However, these studies did not directly account for sampling bias, which may artificially decrease similarity and increase turnover between regions. Our analysis used abundance-based data to account for sampling intensity and was unable to support any hypothesis of multiple distinct faunas; earlier hypothesized faunal delineations were likely a sampling artifact. Our results indicate a low beta diversity and support a single dinosaur community within the entire Western Interior region of latest Cretaceous North America. Homogeneous environments are a known driver of low modern beta diversities, and the warm equable climate of the late Cretaceous modulated by the epicontenental seaway is inferred to be an underlying influence on the low beta diversity of this ancient ecosystem. PMID:20404176

  5. An overview of the dinosaur fossil record from Chile

    NASA Astrophysics Data System (ADS)

    Rubilar-Rogers, David; Otero, Rodrigo A.; Yury-Yáñez, Roberto E.; Vargas, Alexander O.; Gutstein, Carolina S.

    2012-08-01

    In Chile, the record of dinosaurs in Jurassic and Cretaceous sediments is often restricted to footprints, with few skeletal remains. Tetanuran theropods are known in the Upper Jurassic, and bones of titanosaur sauropods in the Late Cretaceous, including partial skeletons (e.g. Atacamatitan chilensis Kellner et al.). Also from the late Cretaceous, an ornithopod vertebra, a pair of theropod teeth and one tarsometatarsus of a gaviiform bird (Neogaeornis wetzeli Lambrecht) have been reported. The Cenozoic fossil record comprises abundant and well-preserved marine birds from Eocene and Miocene units, with a specially abundant record of Sphenisciformes and less frequently, Procellariiformes. There is an excellent Miocene-Pliocene record of other birds such as Odontopterygiformes, including the most complete skeleton ever found of a pelagornithid, Pelagornis chilensis Mayr and Rubilar-Rogers. Fossil birds are also known from Pliocene and Pleistocene strata. A remarkable collection of birds was discovered in lacustrine sediments of late Pleistocene age associated to human activity. The perspectives in the study of dinosaurs in Chile are promising because plenty of material stored in institutional collections is not described yet. The record of Chilean dinosaurs is relevant for understanding the dynamics and evolution of this group of terrestrial animals in the western edge of Gondwana, while Cenozoic birds from the Region may contribute to the understanding of current biogeography for instance, the effect of the emergence and establishment of the Humboldt Current.

  6. Retrodeformation and muscular reconstruction of ornithomimosaurian dinosaur crania.

    PubMed

    Cuff, Andrew R; 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 brevipesBarsbold, 1981 and the ornithomimids Struthiomimus altusLambe, 1902 and Ornithomimus edmontonicusSternberg, 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

  7. Low beta diversity of Maastrichtian dinosaurs of North America

    PubMed Central

    Vavrek, Matthew J.; Larsson, Hans C. E.

    2010-01-01

    Beta diversity is an important component of large-scale patterns of biodiversity, but its explicit examination is more difficult than that of alpha diversity. Only recently have data sets large enough been presented to begin assessing global patterns of species turnover, especially in the fossil record. We present here an analysis of beta diversity of a Maastrichtian (71–65 million years old) assemblage of dinosaurs from the Western Interior of North America, a region that covers ≈1.5 × 106 km2, borders an epicontinental sea, and spans ≈20° of latitude. Previous qualitative analyses have suggested regional groupings of these dinosaurs and generally concluded that there were multiple distinct faunal regions. However, these studies did not directly account for sampling bias, which may artificially decrease similarity and increase turnover between regions. Our analysis used abundance-based data to account for sampling intensity and was unable to support any hypothesis of multiple distinct faunas; earlier hypothesized faunal delineations were likely a sampling artifact. Our results indicate a low beta diversity and support a single dinosaur community within the entire Western Interior region of latest Cretaceous North America. Homogeneous environments are a known driver of low modern beta diversities, and the warm equable climate of the late Cretaceous modulated by the epicontenental seaway is inferred to be an underlying influence on the low beta diversity of this ancient ecosystem. PMID:20404176

  8. 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

  9. 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

  10. Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

    PubMed

    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

  11. 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. PMID:26774070

  12. A Late Cretaceous ceratopsian dinosaur from Europe with Asian affinities.

    PubMed

    Osi, Attila; Butler, Richard J; Weishampel, David B

    2010-05-27

    Ceratopsians (horned dinosaurs) represent a highly diverse and abundant radiation of non-avian dinosaurs known primarily from the Cretaceous period (65-145 million years ago). This radiation has been considered to be geographically limited to Asia and western North America, with only controversial remains reported from other continents. Here we describe new ceratopsian cranial material from the Late Cretaceous of Iharkút, Hungary, from a coronosaurian ceratopsian, Ajkaceratops kozmai. Ajkaceratops is most similar to 'bagaceratopsids' such as Bagaceratops and Magnirostris, previously known only from Late Cretaceous east Asia. The new material unambiguously demonstrates that ceratopsians occupied Late Cretaceous Europe and, when considered with the recent discovery of possible leptoceratopsid teeth from Sweden, indicates that the clade may have reached Europe on at least two independent occasions. European Late Cretaceous dinosaur faunas have been characterized as consisting of a mix of endemic 'relictual' taxa and 'Gondwanan' taxa, with typical Asian and North American groups largely absent. Ajkaceratops demonstrates that this prevailing biogeographical hypothesis is overly simplified and requires reassessment. Iharkút was part of the western Tethyan archipelago, a tectonically complex series of island chains between Africa and Europe, and the occurrence of a coronosaurian ceratopsian in this locality may represent an early Late Cretaceous 'island-hopping' dispersal across the Tethys Ocean. PMID:20505726

  13. 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 development of quadrupedal locomotion via a limited number of functional pathways. Functional anatomy appears to have had a greater effect on moment arms than phylogeny, and the differences identified between individual taxa and individual clades may relate to differences in locomotor performance required for living in different environments or for clade-specific behaviours. PMID:24251809

  14. 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 differed markedly from the present. Studies of past biotas and their changes may elucidate the role of climatic and geographic factors in driving changes in species distributions, ecosystem organization, and evolutionary dynamics over time.

  15. 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. PMID:18195356

  16. 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

  17. Somatic Cell Reprogramming into Cardiovascular Lineages

    PubMed Central

    Chen, Jenny X.; Plonowska, Karolina; Wu, Sean M.

    2015-01-01

    Ischemic cardiac disease is the leading cause of death in the developed world. The inability of the adult mammalian heart to adequately repair itself has motivated stem cell researchers to explore various strategies to regenerate cardiomyocytes after myocardial infarction. Over the past century, progressive gains in our knowledge about the cellular mechanisms governing fate determination have led to recent advances in cellular reprogramming. The identification of specific factors capable of inducing pluripotent phenotype in somatic cells as well as factors that can directly reprogram somatic cells into cardiomyocytes suggests the potential for these approaches to translate into clinical therapies in the future. While conceptually appealing, the field of cell lineage reprogramming is in its infancy and further research will be needed to improve the efficiency of the reprogramming process and the fidelity of the reprogrammed cells to their in vivo counterpart. PMID:24764131

  18. The melanocyte lineage in development and disease

    PubMed Central

    Mort, Richard L.; Jackson, Ian J.; Patton, E. Elizabeth

    2015-01-01

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. PMID:25670789

  19. Phylogeny, Histology and Inferred Body Size Evolution in a New Rhabdodontid Dinosaur from the Late Cretaceous of Hungary

    PubMed Central

    Ősi, Attila; Prondvai, Edina; Butler, Richard; Weishampel, David B.

    2012-01-01

    Background Rhabdodontid ornithopod dinosaurs are characteristic elements of Late Cretaceous European vertebrate faunas and were previously collected from lower Campanian to Maastrichtian continental deposits. Phylogenetic analyses have placed rhabdodontids among basal ornithopods as the sister taxon to the clade consisting of Tenontosaurus, Dryosaurus, Camptosaurus, and Iguanodon. Recent studies considered Zalmoxes, the best known representative of the clade, to be significantly smaller than closely related ornithopods such as Tenontosaurus, Camptosaurus, or Rhabdodon, and concluded that it was probably an island dwarf that inhabited the Maastrichtian Haţeg Island. Methodology/Principal Findings Rhabdodontid remains from the Santonian of western Hungary provide evidence for a new, small-bodied form, which we assign to Mochlodon vorosi n. sp. The new species is most similar to the early Campanian M. suessi from Austria, and the close affinities of the two species is further supported by the results of a global phylogenetic analysis of ornithischian dinosaurs. Bone histological studies of representatives of all rhabdodontids indicate a similar adult body length of 1.6–1.8 m in the Hungarian and Austrian species, 2.4–2.5 m in the subadults of both Zalmoxes robustus and Z. shqiperorum and a much larger, 5–6 m adult body length in Rhabdodon. Phylogenetic mapping of femoral lengths onto the results of the phylogenetic analysis suggests a femoral length of around 340 mm as the ancestral state for Rhabdodontidae, close to the adult femoral lengths known for Zalmoxes (320–333 mm). Conclusions/Significance Our analysis of body size evolution does not support the hypothesis of autapomorhic nanism for Zalmoxes. However, Rhabdodon is reconstructed as having undergone autapomorphic giantism and the reconstructed small femoral length (245 mm) of Mochlodon is consistent with a reduction in size relative to the ancestral rhabdodontid condition. Our results imply a pre-Santonian divergence between western and eastern rhabdodontid lineages within the western Tethyan archipelago. PMID:23028518

  20. Glycogen Synthase Kinase 3β and Activin/Nodal Inhibition in Human Embryonic Stem Cells Induces a Pre-Neuroepithelial State That Is Required for Specification to a Floor Plate Cell Lineage

    PubMed Central

    Denham, Mark; Bye, Chris; Leung, Jessie; Conley, Brock J; Thompson, Lachlan H; Dottori, Mirella

    2012-01-01

    The floor plate is one of the major organizers of the developing nervous system through its secretion of sonic hedgehog (Shh). Although the floor plate is located within the neural tube, the derivation of the floor plate during development is still debatable and some studies suggest that floor plate cells are specified by Shh in a temporarily restricted window different to neuroepithelial cells. Using human embryonic stem cells (hESC) as a model of neurogenesis, we sought to determine how floor plate cells may be temporarily specified by SHH signaling during human embryogenesis. We found that inhibition of both GSK3β and activin/nodal pathways in hESC induces a cellular state of SOX2+/PAX6− expression, we describe as “pre-neuroepithelial.” Exposure of SHH during this pre-neuroepithelial period causes the expression of GLI transcription factors to function as activators and consequently upregulate expression of the floor plate marker, FOXA2, while a