RunX1-induced silencing of non-muscle myosinheavy chain IIB contributes to megakaryocytepolyploidization

摘要

Megakaryocytes are unique mammalian cells that undergo polyploidization (endomitosis)during differentiation, leading to an increase in cell size and protein production that precedesplatelet production. Recent evidence demonstrates that endomitosis is a consequence ofa late failure in cytokinesis associated with a contractile ring defect. Here we show that thenon-muscle myosin IIB heavy chain (mYH10) is expressed in immature megakaryocytes andspecifically localizes in the contractile ring. mYH10 downmodulation by short hairpin RnAincreases polyploidization by inhibiting the return of 4n cells to 2n, but other regulators, suchas of the G1/s transition, might regulate further polyploidization of the 4n cells. Conversely,re-expression of mYH10 in the megakaryocytes prevents polyploidization and the transitionof 2n to 4n cells. During polyploidization, mYH10 expression is repressed by the majormegakaryocyte transcription factor RunX1. Thus, RunX1-mediated silencing of mYH10 isrequired for the switch from mitosis to endomitosis, linking polyploidization with megakaryocytedifferentiation.