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

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 (Pro...

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Main Authors: Jingqiang Wang, Chunye Liu, Lingli He, Zhiyao Xie, Lanyue Bai, Wentao Yu, Zuoyun Wang, Yi Lu, Dong Gao, Junfen Fu, Lei Zhang, Yi Arial Zeng
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/75449
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author Jingqiang Wang
Chunye Liu
Lingli He
Zhiyao Xie
Lanyue Bai
Wentao Yu
Zuoyun Wang
Yi Lu
Dong Gao
Junfen Fu
Lei Zhang
Yi Arial Zeng
author_facet Jingqiang Wang
Chunye Liu
Lingli He
Zhiyao Xie
Lanyue Bai
Wentao Yu
Zuoyun Wang
Yi Lu
Dong Gao
Junfen Fu
Lei Zhang
Yi Arial Zeng
author_sort Jingqiang Wang
collection DOAJ
description 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.
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spelling doaj.art-91385240a3f54866ab713b7e7816a3012022-12-22T03:51:00ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.75449Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repairJingqiang Wang0https://orcid.org/0000-0003-1670-7759Chunye Liu1https://orcid.org/0000-0001-7167-6735Lingli He2Zhiyao Xie3Lanyue Bai4Wentao Yu5Zuoyun Wang6Yi Lu7Dong Gao8Junfen Fu9Lei Zhang10https://orcid.org/0000-0003-2566-6493Yi Arial Zeng11https://orcid.org/0000-0003-1898-8099Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China; 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaHuman Anatomy & Histoembryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaState 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, ChinaState 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, ChinaChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, ChinaState 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; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaState 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; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, ChinaOvarian 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.https://elifesciences.org/articles/75449ovarian surface epitheliumovulatory rupture repairadult stem cellsYAPProcr
spellingShingle Jingqiang Wang
Chunye Liu
Lingli He
Zhiyao Xie
Lanyue Bai
Wentao Yu
Zuoyun Wang
Yi Lu
Dong Gao
Junfen Fu
Lei Zhang
Yi Arial Zeng
Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
eLife
ovarian surface epithelium
ovulatory rupture repair
adult stem cells
YAP
Procr
title Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
title_full Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
title_fullStr Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
title_full_unstemmed Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
title_short Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
title_sort selective yap activation in procr cells is essential for ovarian stem progenitor expansion and epithelium repair
topic ovarian surface epithelium
ovulatory rupture repair
adult stem cells
YAP
Procr
url https://elifesciences.org/articles/75449
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