RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization

Larissa Lordier, Dominique Bluteau, Abdelali Jalil, Céline Legrand, Jiajia Pan, Philippe Rameau, Dima Jouni, Olivier Bluteau, Thomas Mercher, Catherine Leon, Christian Gachet, Najet Debili, William Vainchenker (), Hana Raslova and Yunhua Chang
Additional contact information
Larissa Lordier: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Dominique Bluteau: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Abdelali Jalil: Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Céline Legrand: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Jiajia Pan: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Philippe Rameau: Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Dima Jouni: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Olivier Bluteau: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Thomas Mercher: Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Catherine Leon: INSERM UMR S949, Université de Strasbourg
Christian Gachet: INSERM UMR S949, Université de Strasbourg
Najet Debili: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
William Vainchenker: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Hana Raslova: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
Yunhua Chang: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: Abstract Megakaryocytes are unique mammalian cells that undergo polyploidization (endomitosis) during differentiation, leading to an increase in cell size and protein production that precedes platelet production. Recent evidence demonstrates that endomitosis is a consequence of a late failure in cytokinesis associated with a contractile ring defect. Here we show that the non-muscle myosin IIB heavy chain (MYH10) is expressed in immature megakaryocytes and specifically localizes in the contractile ring. MYH10 downmodulation by short hairpin RNA increases polyploidization by inhibiting the return of 4N cells to 2N, but other regulators, such as 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 transition of 2N to 4N cells. During polyploidization, MYH10 expression is repressed by the major megakaryocyte transcription factor RUNX1. Thus, RUNX1-mediated silencing of MYH10 is required for the switch from mitosis to endomitosis, linking polyploidization with megakaryocyte differentiation.

Date: 2012
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DOI: 10.1038/ncomms1704

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