megakaryopoiesis

Megakaryopoiesis is the process by which megakaryocytes develop from hematopoietic stem and progenitor cells in the bone marrow, ultimately supplying platelets essential for hemostasis. Megakaryocytes are large, polyploid cells that reside in the marrow and extend cytoplasmic processes into sinusoidal vessels, from which platelets are released.

Development proceeds through several stages. Hematopoietic stem cells differentiate into common myeloid progenitors and then megakaryocyte-erythroid progenitors. From there, megakaryocyte progenitors give rise to megakaryoblasts, promegakaryocytes, and finally mature megakaryocytes. A hallmark of megakaryopoiesis is endomitosis, a replication of DNA without nuclear division, producing polyploid megakaryocytes with multiple copies of the genome. Cytoplasmic maturation involves expansion of organelles and formation of the demarcation membrane system to support platelet production. Proplatelets form and extend through the osseous marrow cavity into blood vessels, where shear forces facilitate platelet release.

Regulation is dominated by thrombopoietin (TPO), the master growth factor for megakaryopoiesis. TPO binds the MPL receptor on progenitors and megakaryocytes, promoting proliferation and maturation. Hepatic production of TPO and its clearance by platelets via MPL create a feedback loop that adjusts platelet production to demand. Additional cytokines such as interleukins 3, 6 and 11, and stem cell factor support various stages of development. The bone marrow microenvironment also modulates differentiation through interactions with stromal and endothelial cells and osteoblasts.

Clinical relevance includes disorders of megakaryopoiesis contributing to thrombocytopenia or thrombocytosis. Abnormal megakaryocyte development or function underlies several myeloid neoplasms, such as essential thrombocythemia, and affects platelet quantity and quality.