4.4 Article

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

Journal

CELL AND TISSUE RESEARCH
Volume 389, Issue 3, Pages 573-585

Publisher

SPRINGER
DOI: 10.1007/s00441-022-03653-6

Keywords

CDC42; Human trophoblast stem cell; Placenta; YAP; EZRIN; Recurrent spontaneous abortion

Categories

Funding

  1. National Natural Science Foundation of China [81830045, 82071652, 81801446, 31971071]
  2. National Key R&D Program of China [2017YFC1001402, 2018YFC1004102, 2016YFC1000405]
  3. Science and Technology Projects in Guangzhou [202102010005, 202102010006]
  4. Guangzhou Municipal Health Commission [2019GX03]
  5. General Program of Guangdong Province Natural Science Foundation [2021A1515011039, 2020A1515010273]

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This study reveals the importance of the CDC42/EZRIN/YAP pathway in placental development. Deficiency of CDC42 leads to the differentiation and inhibition of proliferation in hTSCs, as well as abnormal expression of EZRIN, YAP, and Ki67.
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.

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