Overexpression of cyclin D1 moderately increases ploidy in megakaryocytes

Abstract

BACKGROUND AND OBJECTIVES: Megakaryocytes undergo a unique cell cycle by which they replicate their complete genome many times in the absence of cytokinesis. In the search for regulators of the endomitotic cell cycle, we previously produced mice transgenic for cyclin D3 to identify this cyclin as able to enhance ploidy and to increase the number of differentiated cells in the megakaryocytic lineage. Of the D-type cyclins, cyclin D3 and to a much lesser extent cyclin D1, are present in megakaryocytes undergoing endomitosis and these cyclins are, respectively, markedly and moderately upregulated following exposure to the ploidy-promoting factor, Mpl-ligand. Our objective was to explore whether cyclin D1 can mimic the effect of cyclin D3 on ploidy in megakaryocytes. DESIGN AND METHODS: We generated transgenic mice overexpressing cyclin D1 in megakaryocytes and analyzed megakaryocyte ploidy, number and platelet levels in these mice and control mice. RESULTS: We show that transgenic mice in which cyclin D1 is overexpressed in megakaryocytes display higher ploidy level than the control mice, with no change in the number of differentiated cells of the megakaryocytic series, or in platelet level. INTERPRETATION AND CONCLUSIONS: Our models support a key role for D-type cyclins in the endomitotic cell cycle, and also indicate that although cyclin D3, from among the D cyclins, is unique in its high levels of expression in megakaryocytes, it is not unique in its ability to promote polyploidization.