The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery.
The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery.
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DOI：
10.1016/j.jbc.2022.101701
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Qin J
中科院分区：
文献类型：
--
作者：
Wang C;Hao K;Dong L;Wang J;Zhao L;Xu L;Xia Y;Jiang Q;Qin J
越来越多的证据表明，无限的自我更新能力和多能性，胚胎干细胞（ESCs）的两个独特的属性，是内在联系到细胞周期控制。然而，协调细胞命运决定和细胞周期调控的确切机制仍有待充分探索。在这里，使用CRISPR/Cas9介导的基因组编辑，我们表明在ESC中，细胞周期调节MuvB复合物Lin 54或Lin 52的组分的缺乏，而不是Lin 9或Lin 37，触发G2/M停滞，多能性丧失和自发分化。这些表型的进一步解剖表明，这种细胞周期阻滞伴随着中内胚层谱系特异性基因的逐渐激活。引人注目的是，在Lin 54-null ESCs中观察到的异常部分但显著地被编码G2/M蛋白Cyclin B1和Cdk 1的基因的异位共表达所拯救。因此，我们的研究为MuvB复合物通过调节细胞周期机制决定细胞命运的机制提供了新的见解。
Increasing evidences indicate that unlimited capacity for self-renewal and pluripotency, two unique properties of embryonic stem cells (ESCs), are intrinsically linked to cell cycle control. However, the precise mechanisms coordinating cell fate decisions and cell cycle regulation remain to be fully explored. Here, using CRISPR/Cas9-mediated genome editing, we show that in ESCs, deficiency of components of the cell cycle regulatory MuvB complex Lin54 or Lin52, but not Lin9 or Lin37, triggers G2/M arrest, loss of pluripotency, and spontaneous differentiation. Further dissection of these phenotypes demonstrated that this cell cycle arrest is accompanied by the gradual activation of mesoendodermal lineage-specifying genes. Strikingly, the abnormalities observed in Lin54-null ESCs were partially but significantly rescued by ectopic coexpression of genes encoding G2/M proteins Cyclin B1 and Cdk1. Thus, our study provides new insights into the mechanisms by which the MuvB complex determines cell fate through regulation of the cell cycle machinery.
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