CHIR99021 Enhances the Proliferation of Mouse Female Germline Stem Cells Via Modulating ERCC2.

Abstract

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.