Megakaryocytopoiesis: From marrow stem cells to circulating platelets

Aaron Tomer, Varda Deutsch

Research output: Contribution to journalReview articlepeer-review


Megakaryocytopoiesis involves the commitment of hematopoietic stem cells, proliferation and differentiation of the megakaryocytic progenitors, and cell maturation including endoreduplication and cytoplasmic acquisition of structural and functional properties of platelets. Megakaryocytopoiesis is primarily controlled by thrombopoietin (TPO), which induces the expansion of early progenitors, as well as, the proliferation, endoreduplication and differentiation of megakaryocytes (MKs). Thrombopoietin avidly binds to the c-Mpl receptors on platelets and MKs, and the circulating levels of unbound TPO induce concentration-dependent proliferation and maturation of MK progenitors. Accordingly, decrease in platelet turnover rate results in increased concentration of unbound TPO, enabling the compensatory response of marrow MKs to increased demand for peripheral blood platelets. The process of megakaryocytopoiesis is also mediated by multiple pleiotropic hematopoietic growth factors which include the stem cell factor - c-kit ligand, interleukin-3 (IL-3), IL-6, IL-11, granulocyte-macrophage colony-stimulating factor (GM-CSF) and FGF, as well as chemokines such as SDF-1 with its receptor CXCR-4. The stimulatory effect of the regulating factors is mediated by a concerted action of specific transcription factors such as GATA-1 and FOG, Runx1, Ets and Nuclear Factor-Erythroid-2, while C-myb plays a central negative regulatory role. The demise of senescent MKs involves a specialized form of apoptosis during the processes of proplatelet formation and platelet release. In this review, the regulation of megakaryocytopoiesis with the quantitative alterations in the megakaryocytic cells and platelet production, in both humans and animal models, is discussed.

Original languageEnglish
Pages (from-to)1-22
Number of pages22
JournalJournal of Stem Cells
Issue number1
StatePublished - 1 Dec 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology
  • Transplantation


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