Sun S, Zimmet J M, Toselli P, Thompson A, Jackson C W, Ravid K
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
Haematologica. 2001 Jan;86(1):17-23.
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.
We generated transgenic mice overexpressing cyclin D1 in megakaryocytes and analyzed megakaryocyte ploidy, number and platelet levels in these mice and control mice.
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.
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.
巨核细胞经历独特的细胞周期，在此过程中它们在没有胞质分裂的情况下多次复制其完整基因组。在寻找核内有丝分裂细胞周期的调节因子时，我们之前培育了细胞周期蛋白D3转基因小鼠，以确定这种细胞周期蛋白能够提高倍性并增加巨核细胞系中分化细胞的数量。在D型细胞周期蛋白中，细胞周期蛋白D3以及程度小得多的细胞周期蛋白D1存在于进行核内有丝分裂的巨核细胞中，并且在暴露于促进倍性的因子Mpl配体后，这些细胞周期蛋白分别显著和适度上调。我们的目的是探讨细胞周期蛋白D1是否能模拟细胞周期蛋白D3对巨核细胞倍性的影响。
我们培育了在巨核细胞中过表达细胞周期蛋白D1的转基因小鼠，并分析了这些小鼠和对照小鼠的巨核细胞倍性、数量和血小板水平。
我们发现，在巨核细胞中过表达细胞周期蛋白D1的转基因小鼠的倍性水平高于对照小鼠，而巨核细胞系列中分化细胞的数量或血小板水平没有变化。
我们的模型支持D型细胞周期蛋白在核内有丝分裂细胞周期中起关键作用，并且还表明，虽然在D型细胞周期蛋白中，细胞周期蛋白D3在巨核细胞中的高表达水平是独特的，但它在促进多倍体化的能力方面并非独特。
