The evolution of megakaryocytes to platelets.

Megakaryocytes (MKs) arise from pluripotent stem cells by a process of cell division, endoreplication and maturation. Progressively, the MK cytoplasm is invaded by the demarcation membrane system speculated to delimit pre-formed platelets. One theory is that the passage of entire MKs (or fragments) into the blood stream is followed by their physical break-up into platelets in the pulmonary circulation. A second theory is that MKs produce beaded processes (proplatelets) which then separate into platelets. Functionally vital platelet receptors such as GPIIb-IIIa and GPIb-IX complexes are specific markers of the MK lineage. CD34 and CD4 are present in progenitors but progressively disappear as MKs mature. Stroma cells secrete cytokines, produce extracellular matrix proteins and mediate cellular contact interactions that regulate MK development. Studies on thrombopoietin and the use of transgenic mouse models are helping to clarify MK biology.