Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation

被引:7
作者
Shilei, Bi [1 ,2 ,3 ,4 ]
Lizi, Zhang [5 ]
Lijun, Huang [1 ,2 ,3 ,4 ]
Weixu, Ma [1 ,2 ,3 ,4 ]
Nan, Meng [6 ]
Weinan, Deng [1 ,2 ,3 ,4 ]
Yulian, Li [1 ,2 ,3 ,4 ]
Yingyu, Liang [1 ,2 ,3 ,4 ]
Minshan, Huang [1 ,2 ,3 ,4 ]
Pei, Xu [1 ,2 ,3 ,4 ]
Mingxing, Liu [1 ,2 ,3 ,4 ]
Jingsi, Chen [1 ,2 ,3 ,4 ]
Zhaowei, Tu [1 ,2 ,3 ,4 ]
Zhijian, Wang [5 ]
Haibin, Wang [6 ]
Jinhua, Lu [6 ]
Dunjin, Chen [1 ,2 ,3 ,4 ]
Lili, Du [1 ,2 ,3 ,4 ]
机构
[1] Guangzhou Med Univ, Affiliated Hosp 3, Guangdong Prov Key Lab Major Obstetr Dis, Dept Obstet & Gynecol, Guangzhou, Guangdong, Peoples R China
[2] Guangdong Higher Educ Inst, Key Lab Reprod & Genet, Guangzhou, Peoples R China
[3] Guangdong Engn & Technol Res Ctr Maternal Fetal M, Guangzhou, Peoples R China
[4] Guangdong Hong Kong Macao Greater Bay Area Higher, Guangzhou, Peoples R China
[5] Southern Med Univ, Nanfang Hosp, Dept Obstet & Gynecol, Guangzhou, Peoples R China
[6] Xiamen Univ, Sch Med, Fujian Prov Key Lab Reprod Hlth Res, Xiamen, Fujian, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
CDC42; Human trophoblast stem cell; Placenta; YAP; EZRIN; Recurrent spontaneous abortion; HIPPO PATHWAY; TRANSCRIPTION FACTORS; RHO-GTPASES; YAP; DIFFERENTIATION; MIGRATION; YAP/TAZ; TENSION; ACTIN; RAC1;
D O I
10.1007/s00441-022-03653-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:573 / 585
页数:13
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