Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):757-62. doi: 10.1016/j.bbrc.2012.11.075. Epub 2012 Dec 1.
Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1(GT/GT)) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1(GT/GT) TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.
胎盘滋养层干细胞（TS）向滋养层巨细胞（TG）的分化伴随着从有丝分裂细胞周期向内细胞周期的转变。在这里，我们报告说，细胞周期蛋白依赖性激酶 1（Cdh1）是有丝分裂/内细胞周期过渡时促进复合物/环体（APC/C）的调节因子，它负调控有丝分裂进入。从纯合 Cdh1 基因捕获（Cdh1(GT/GT)）的胚胎中分离出的 TS 细胞积累了有丝分裂周期蛋白，并在诱导 TS 细胞分化后过早进入有丝分裂，这表明 Cdh1 是从有丝分裂到内细胞周期转变所必需的。此外，Cdh1(GT/GT)TS 细胞和胎盘表现出胎盘分化标记物的异常表达。这些数据突出了 Cdh1 在胎盘分化过程中 G2/M 转换中的重要作用。
