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

作者全名："Wen, Fan; Ding, Yuxi; Wang, Mingming; Du, Jing; Zhang, Shen; Kee, Kehkooi"

作者地址："[Wen, Fan; Ding, Yuxi; Wang, Mingming; Du, Jing; Kee, Kehkooi] Tsinghua Univ, Sch Med, State Key Lab Complex Severe & Rare Dis, Beijing, Peoples R China; [Wen, Fan; Ding, Yuxi; Wang, Mingming; Du, Jing; Kee, Kehkooi] Tsinghua Univ, SXMU Tsinghua Collaborat Innovat Ctr Frontier Med, Sch Med, Beijing, Peoples R China; [Wen, Fan; Ding, Yuxi; Wang, Mingming; Du, Jing; Kee, Kehkooi] Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China; [Zhang, Shen] Wenzhou Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Wenzhou, Peoples R China; [Zhang, Shen] Chongqing Med Univ, Affiliated Hosp 2, Reprod Med Ctr, Dept Obstet & Gynecol, Chongqing, Peoples R China"

通信作者："Kee, K (通讯作者)，Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China."

来源：CELL PROLIFERATION

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001138095000001

JCR分区：Q2

影响因子：8.5

年份：2024

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期号：　

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文献类型：Article; Early Access

关键词：　

摘要："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."

基金机构：Tsinghua-Peking Center for Life Sciences

基金资助正文：No Statement Availabler No Statement Availabler No Statement Available