Jia Qingling, Tian Geng G, Li Xiaoyong, Wu Ji
Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China.
School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Reprod Sci. 2025 May 29. doi: 10.1007/s43032-025-01877-9.
Female germline stem cells (FGSCs) are a type of adult stem cell that exist in mammalian ovaries and can self-renew and differentiate into mature oocytes. Small molecule compounds are substances with a molecular weight less than 900 Daltons that can affect cellular functions and behaviors through various mechanisms. Here, we identified three compounds, Agrin, CHIR99021 (CHIR), and Testosterone, that can enhance the proliferation of FGSCs, with CHIR demonstrating superior efficacy. To elucidate the mechanism underlying CHIR's role in promoting FGSCs proliferation, we conducted RNA sequencing and tandem mass tag (TMT)-based quantitative proteomic profiling on FGSCs both with and without CHIR exposure. By integrating the data from these two sequencing approaches, we employed gene set enrichment analysis (GSEA) and identified Ercc2 as a crucial gene modulated by CHIR-induced FGSC proliferation. Further experiments confirmed that CHIR enhanced FGSCs proliferation via ERCC2. This research deepens our comprehension of the proliferative mechanisms of FGSCs and lays a theoretical foundation for future investigations into the developmental mechanisms of female germ cells, as well as the development of infertility treatments.
雌性生殖系干细胞（FGSCs）是一种存在于哺乳动物卵巢中的成体干细胞，能够自我更新并分化为成熟的卵母细胞。小分子化合物是分子量小于900道尔顿的物质，可通过多种机制影响细胞功能和行为。在此，我们鉴定出三种化合物，聚集蛋白、CHIR99021（CHIR）和睾酮，它们能够增强FGSCs的增殖，其中CHIR表现出卓越的功效。为阐明CHIR促进FGSCs增殖作用的潜在机制，我们对暴露于CHIR和未暴露于CHIR的FGSCs进行了RNA测序和基于串联质谱标签（TMT）的定量蛋白质组分析。通过整合这两种测序方法的数据，我们采用基因集富集分析（GSEA）并确定Ercc2是受CHIR诱导的FGSC增殖调控的关键基因。进一步的实验证实，CHIR通过ERCC2增强FGSCs的增殖。这项研究加深了我们对FGSCs增殖机制的理解，为未来对雌性生殖细胞发育机制以及不孕症治疗方法的研究奠定了理论基础。
