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

Ng, AP; Kauppi, M; Metcalf, D; Di Rago, L; Hyland, CD; Alexander, WS

Author(s): Ng, AP; Kauppi, M; Metcalf, D; Di Rago, L; Hyland, CD; Alexander, WS;
Details: Publication Year 2012-02-14,Volume 109,Issue #7,Page 2364-2369
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
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(-)Fc gamma RII/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)endoglinlo 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.
Publisher: NATL ACAD SCIENCES
Keywords: HEMATOPOIETIC STEM-CELLS; LINEAGES
Research Division(s): Cancer And Haematology
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289343/
Publisher's Version: https://doi.org/10.1073/pnas.1121385109

Creation Date: 2012-02-14 12:00:00