Presence of a defect in karyokinesis during megakaryocyte endomitosis

Abstract

Megakaryocyte is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, a process corresponding to a late failure of cytokinesis with a backward movement of the daughter cells. Generally, a pure defect in cytokinesis produces a multinucleated cell, but megakaryocytes are characterized by a single polylobulated nucleus with a 2^N ploidy. Here, we show the existence of a defect in karyokinesis during the endomitotic process. From late telophase until the reversal of cytokinesis, some dipolar mitosis/endomitosis and most multipolar endomitosis present a thin DNA link between the segregated chromosomes surrounded by an incomplete nuclear membrane formation, which implies that sister chromatid separation is not complete. This observation may explain why polyploid megakaryocytes display a single polylobulated nucleus along with an increase in ploidy.

Keywords: :

• megakaryocyte
• endomitosis
• polyploidy
• karyokinesis
• cytokinesis

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank F. Wendling for her critical review of the manuscript. We thank the platform of Imaging and Cytometry of Institut Gustave Roussy (IFR54) for the technical support. This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM) and by grants from la Ligue Nationale Contre le Cancer (LNCC ; Equipe labelisée 2010, W.V.) and from the Agence Nationale de la Recherche (ANR blanc W.V. and ANR Jeune chercheur Y.C.). Jiajia Pan was supported by China Scholarship Council. Larissa Lordier, Jiajia Pan, Valeria Naim and Abdelali Jalil performed research. Idinath Badirou, Philippe Rameau, Jerôme Larghero and Najet Debili contributed to perform experiments. Yunhua Chang designed/performed research and wrote the paper. William Vaincheker designed research and wrote the paper.