2. Academic Validation
  3. Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair

Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair

  • Elife. 2022 Mar 14;11:e75449. doi: 10.7554/eLife.75449.
Jingqiang Wang  # 1 2,  Chunye Liu  # 2,  Lingli He  # 2,  Zhiyao Xie 2,  Lanyue Bai 2,  Wentao Yu 2,  Zuoyun Wang 3,  Yi Lu 2,  Dong Gao 2,  Junfen Fu 1,  Lei Zhang 2 4 5,  Yi Arial Zeng 2 4
Affiliations

Affiliations

  • 1 Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
  • 2 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 3 Human Anatomy & Histoembryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • 4 School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.
  • 5 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • # Contributed equally.
PMID: 35285801 DOI: 10.7554/eLife.75449
Abstract

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and OSE stem cells rapidly generate new cells for the repair. How the stem cell activation is triggered by the rupture and promptly turns on proliferation is unclear. Our previous study has identified that Protein C Receptor (Procr) marks OSE progenitors. In this study, we observed decreased adherent junction and selective activation of YAP signaling in Procr progenitors at OSE rupture site. OSE repair is impeded upon deletion of Yap1 in these progenitors. Interestingly, Procr+ progenitors show lower expression of Vgll4, an antagonist of YAP signaling. Overexpression of Vgll4 in Procr+ cells hampers OSE repair and progenitor proliferation, indicating that selective low Vgll4 expression in Procr+ progenitors is critical for OSE repair. In addition, YAP activation promotes transcription of the OSE stemness gene Procr. The combination of increased cell division and Procr expression leads to expansion of Procr+ progenitors surrounding the rupture site. These results illustrate a YAP-dependent mechanism by which the stem/progenitor cells recognize the murine ovulatory rupture, and rapidly multiply their numbers, highlighting a YAP-induced stem cell expansion strategy.

Keywords

Procr; YAP; adult stem cells; developmental biology; mouse; ovarian surface epithelium; ovulatory rupture repair.

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