Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation
Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation
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DOI：
10.1007/s00441-022-03653-6
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发表时间：
2022-06
影响因子：
3.6
通讯作者：
Shilei Bi;Zhang Lizi;Hu Lijun;Ma Weixu;Meng Nan;Weinan Deng;Yulian Li;Yi Liang;Minshan Huang;Xu Pei;Mingxing Liu;Jingsi Chen;Zhaowei Tu;Zhijian Wang;Haibin Wang;Jinhua Lu;Dunjin Chen;D. Lili
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文献类型：
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作者：
Shilei Bi;Zhang Lizi;Hu Lijun;Ma Weixu;Meng Nan;Weinan Deng;Yulian Li;Yi Liang;Minshan Huang;Xu Pei;Mingxing Liu;Jingsi Chen;Zhaowei Tu;Zhijian Wang;Haibin Wang;Jinhua Lu;Dunjin Chen;D. Lili
胎盘发育不良增加复发性流产（RSA）的风险。然而，调节胎盘发育的潜在机制仍不清楚。在这项研究中，我们发现，与健康对照组相比，RSA样本的绒毛组织中CDC 42的表达降低。进一步的研究表明，CDC 42缺陷导致人滋养层干细胞（hTSCs）的分化，并抑制其增殖。hTSC中雅普和EZRIN的遗传操作揭示了CDC 42调节hTSC的干性和增殖;这依赖于EZRIN，其将雅普易位到细胞核中。此外，EZRIN、雅普和Ki 67的表达模式在RSA样品的绒毛组织中也是异常的，与体外实验一致。总之，这些发现表明，CDC 42/EZRIN/雅普途径在胎盘发育中起着重要作用。
Placental dysplasia increases the risk of recurrent spontaneous abortion (RSA). However, the underlying mechanism regulating placental development remains unclear. In this study, we showed that the expression of CDC42 was decreased in the villous tissue of RSA samples compared to healthy controls. Further examination demonstrated that CDC42 deficiency led to the differentiation of human trophoblast stem cells (hTSCs) and inhibited their proliferation. Genetic manipulation of YAP and EZRIN in hTSCs revealed that CDC42 regulates the stemness and proliferation of hTSCs; this is dependent on EZRIN, which translocates YAP into the nucleus. Moreover, the expression pattern of EZRIN, YAP, and Ki67 was also abnormal in the villous tissue of RSA samples, consistent with in vitro experiments. In summary, these findings suggest that the CDC42/EZRIN/YAP pathway plays an important role in placental development.