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    Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential

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    Characterization of TPO-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential (1.056Mb)

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    Author
    Ng, AP; Kauppi, M; Metcalf, D; Di Rago, L; Hyland, CD; Alexander, WS
    Date
    2012-02-14
    Source Title
    Proceedings of the National Academy of Sciences of USA
    PLoS Genetics
    Publisher
    NATL ACAD SCIENCES
    University of Melbourne Author/s
    Alexander, Warren; Ng, Ashley; METCALF, DONALD; Kauppi, Maria
    Affiliation
    The Walter and Eliza Hall Institute of Medical Research
    Department of Medical Biology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Ng, A. P., Kauppi, M., Metcalf, D., Di Rago, L., Hyland, C. D. & Alexander, W. S. (2012). Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109 (7), pp.2364-2369. https://doi.org/10.1073/pnas.1121385109.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/29079
    DOI
    10.1073/pnas.1121385109
    Description

    © 2012 Ashley P. Ng, Maria Kauppi, Donald Metcalf, Ladina Di Rago, Craig D. Hyland & Warren S. Alexander

     

    Published as “Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential” in Proceedings of the National Academy of Sciences (PNAS) of the United States of America. The definitive version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289343/

     
    Abstract
    Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate the production of precise numbers of mature blood cells of diverse functional lineages. Identification of cell-surface antigen expression associated with hematopoietic lineage restriction has allowed prospective isolation of progenitor cells with defined hematopoietic potential. To clarify further the cellular origins of megakaryocyte commitment, we assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in the adult mouse bone marrow. We show that megakaryocytes arise from CD150(+) bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3(-) fraction of the pregranulocyte-macrophage population. We define a bipotential erythroid-megakaryocyte progenitor population, the CD150(+)CD9(lo)endoglin(lo) fraction of Lin(-)cKit(+)IL7 receptor alpha(-)FcγRII/III(lo)Sca1(-) cells, which contains the bulk of the megakaryocyte colony-forming capacity of the bone marrow, including bipotential megakaryocyte-erythroid colony-forming capacity, and can generate both erythrocytes and platelets efficiently in vivo. This fraction is distinct from the CD150(+)CD9(hi)endoglin(lo) fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150(+)CD9(lo)endoglin(hi) fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that bipotential erythroid-megakaryocyte progenitor and CD150(+)CD9(hi)endoglin(lo) cells are TPO-responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum.
    Keywords
    thrombopoietin; megakaryocyte; progenitor

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