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Thrombopoietin (TPO), the ligand for c-mpl, has recently been demonstrated to be the primary regulator of megakaryocytopoiesis and platelet production. In addition, several studies have demonstrated that c-mpl is expressed on hematopoietic cell populations highly enriched in primitive progenitor cells. Here we summarize and discuss recent studies from our laboratory, as well as others, demonstrating that TPO has effects on primitive hematopoietic progenitor cells. When acting alone, TPO stimulates little or no growth, but promotes viability and suppresses apoptosis of murine multipotent (Lin- Sca-1+) bone marrow progenitor cells in vitro. In addition, TPO directly and potently synergizes with other early acting cytokines (kit ligand, flt3 ligand and interleukin 3) to promote multilineage growth of the same progenitor cell population. Although it remains to be established whether TPO also acts on the long-term reconstituting pluripotent stem cells, these studies combined with progenitor cell studies in c-mpl-deficient mice, suggest that TPO, in addition to its key role in platelet production, might also have an important impact on early hematopoiesis.

Original publication

DOI

10.1002/stem.5530140722

Type

Journal article

Journal

Stem Cells

Publication Date

1996

Volume

14 Suppl 1

Pages

173 - 180

Keywords

Animals, Apoptosis, Blood Platelets, Bone Marrow Cells, Cell Division, Cell Survival, Hematopoietic Stem Cells, Interleukin-3, Membrane Proteins, Mice, Models, Biological, Stem Cell Factor, Thrombopoietin