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

Abstract

Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate 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 further clarify the cellular origins of megakaryocyte commitment, we have 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 pre-granulocyte-macrophage (PreGM) population. We define a bi-potential erythroid-megakaryocyte progenitor population (BEMP), the CD150+CD9loEndoglinlo fraction of Lin-cKit+IL7Rα-FcγRII/IIIloSca1- cells, which contains the bulk of the megakaryocyte colony-forming capacity (CFC) of the bone marrow, including bipotential megakaryocyte-erythroid CFC, and can efficiently generate both erythrocytes and platelets in vivo. This fraction is distinct from the CD150+CD9hiEndoglinlo fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150+CD9loEndoglinhi fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that BEMP and CD150+CD9hiEndoglinlo cells are TPO-responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum.