{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:26:17Z","timestamp":1791044777271,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071597"],"award-info":[{"award-number":["82071597"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To address this problem, it is necessary to induce functional granulosa cells at different stages in vitro. In this study, we established a reprogramming method to induce early\u2010 and late\u2010stage granulosa cells with different steroidogenic abilities. We used an AMH\u2010fluorescence\u2010reporter system to screen candidate factors for cellular reprogramming and generated human induced granulosa\u2010like cells (hiGC) by overexpressing FOXL2 and NR5A1. AMH\u2010EGFP<jats:sup>+<\/jats:sup> hiGC resembled human cumulus cells in transcriptome profiling and secreted high levels of oestrogen and progesterone, similar to late\u2010stage granulosa cells at antral or preovulatory stage. Moreover, we identified CD55 as a cell surface marker that can be used to isolate early\u2010stage granulosa cells. CD55<jats:sup>+<\/jats:sup> AMH\u2010EGFP<jats:sup>\u2010<\/jats:sup> hiGC secreted high levels of oestrogen but low levels of progesterone, and their transcriptome profiles were more similar to early\u2010stage granulosa cells. More importantly, CD55<jats:sup>+<\/jats:sup> hiGC transplantation alleviated polycystic ovary syndrome (PCOS) in a mouse model. Therefore, hiGC provides a cellular model to study the developmental program of human granulosa cells and has potential to treat PCOS.<\/jats:p>","DOI":"10.1111\/cpr.13589","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T07:01:22Z","timestamp":1704783682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>FOXL2<\/scp> and <scp>NR5A1<\/scp> induce human fibroblasts into steroidogenic ovarian granulosa\u2010like cells"],"prefix":"10.1111","volume":"57","author":[{"given":"Fan","family":"Wen","sequence":"first","affiliation":[{"name":"The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU\u2010Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine Tsinghua University  Beijing 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Frontier Medicine; Department of Basic Medical Sciences, School of Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital Wenzhou Medical University  Wenzhou China"},{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6926-7203","authenticated-orcid":false,"given":"Kehkooi","family":"Kee","sequence":"additional","affiliation":[{"name":"The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU\u2010Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine Tsinghua University  Beijing 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