The cellular mechanisms controlling cell fate in self-renewal tissues remain unclear. Cell cycle failure often leads to an apoptosis anti-oncogenic response. We have inactivated Cdk1 or Polo-like-1 kinases, essential targets of the mitotic checkpoints, in the epithelia of skin and oral mucosa. Here, we show that inactivation of the mitotic kinases leading to polyploidy in vivo, produces a fully differentiated epithelium. Cells within the basal layer aberrantly differentiate and contain large or various nuclei. Freshly isolated KO cells were also differentiated and polyploid. However, sustained metaphase arrest downstream of the spindle anaphase checkpoint (SAC) due to abrogation of CDC20 (essential cofactor of anaphase-promoting complex), impaired squamous differentiation and resulted in apoptosis. Therefore, upon prolonged arrest keratinocytes need to slip beyond G2 or mitosis in order to initiate differentiation. The results altogether demonstrate that mitotic checkpoints drive squamous cell fate towards differentiation or apoptosis in response to genetic damage.

中文翻译：

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鳞状分化需要 G2/有丝分裂滑动以避免细胞凋亡。

在自我更新组织中控制细胞命运的细胞机制仍不清楚。细胞周期失败通常会导致细胞凋亡抗癌反应。我们已经灭活了皮肤和口腔粘膜上皮细胞中的 Cdk1 或 Polo-like-1 激酶，它们是有丝分裂检查点的重要目标。在这里，我们表明导致体内多倍体的有丝分裂激酶的失活会产生完全分化的上皮。基底层内的细胞异常分化并含有大的或不同的细胞核。新鲜分离的 KO 细胞也分化和多倍体。然而，由于 CDC20（后期促进复合物的必需辅因子）的废除，纺锤体后期检查点 (SAC) 下游的中期停滞持续，鳞状细胞分化受损并导致细胞凋亡。所以，长时间停滞后，角质形成细胞需要滑过 G2 或有丝分裂才能开始分化。结果完全表明，有丝分裂检查点驱动鳞状细胞命运以响应遗传损伤而分化或凋亡。