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Yes\u2010associated protein (YAP) is a key effector molecule of the Hippo signaling pathway and plays an important role in regulating cell proliferation and liver homeostasis. However, its role in LPCs proliferation and differentiation during liver fibrosis are not well understood. Using immunohistochemistry, immunofluorescence staining, quantitative PCR and Western blotting, we discovered that LPCs expansion and enhanced YAP expression in LPCs in either choline\u2010deficient, ethionine\u2010supplemented (CDE) diet or 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC) diet\u2010induced fibrotic mice, as well as in patients with liver fibrosis. By injecting adeno\u2010associated virus vectors under the transcriptional control of Lgr5 promoter, we found that targeted knockdown of YAP in LPCs attenuated the CDE\/DDC diet\u2010induced ductular reaction and liver fibrosis. Using EdU incorporation and Cell Counting Kit\u20108 assays, we demonstrated that YAP can modulate LPCs proliferation. Importantly, spleen transplantation of YAP\u2010overexpressing LPCs improved their ability to differentiate into hepatocytes and alleviated carbon tetrachloride\u2010induced liver fibrosis. Collectively, our findings indicate that LPCs expansion and differentiation during liver fibrosis could be modulated by YAP, further suggesting the possibility of manipulating YAP expression in LPCs as a potential treatment for chronic liver diseases.<\/jats:p>","DOI":"10.1096\/fj.202201919r","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T04:02:02Z","timestamp":1681876922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Yes\u2010associated protein promotes the proliferation and differentiation of liver progenitor cells during liver fibrosis"],"prefix":"10.1096","volume":"37","author":[{"given":"Zhenyang","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai General Hospital, 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