FOXL2 and NR5A1 induce human fibroblasts into steroidogenic ovarian granulosa-like cells.

Autor: Wen F; The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China., Ding Y; The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China., Wang M; The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China., Du J; The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China., Zhang S; Reproductive Medicine Center, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China., Kee K; The State Key Laboratory for Complex, Severe, and Rare Diseases; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2024 May; Vol. 57 (5), pp. e13589. Date of Electronic Publication: 2024 Jan 08.
DOI: 10.1111/cpr.13589
Abstrakt: 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- and late-stage granulosa cells with different steroidogenic abilities. We used an AMH-fluorescence-reporter system to screen candidate factors for cellular reprogramming and generated human induced granulosa-like cells (hiGC) by overexpressing FOXL2 and NR5A1. AMH-EGFP + hiGC resembled human cumulus cells in transcriptome profiling and secreted high levels of oestrogen and progesterone, similar to late-stage granulosa cells at antral or preovulatory stage. Moreover, we identified CD55 as a cell surface marker that can be used to isolate early-stage granulosa cells. CD55 + AMH-EGFP - hiGC secreted high levels of oestrogen but low levels of progesterone, and their transcriptome profiles were more similar to early-stage granulosa cells. More importantly, CD55 + 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.
(© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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