2. Academic Validation
  3. Metformin Promotes Proliferation of Mouse Female Germline Stem Cells by Histone Acetylation Modification of Traf2

Metformin Promotes Proliferation of Mouse Female Germline Stem Cells by Histone Acetylation Modification of Traf2

  • Stem Cell Rev Rep. 2023 Jun 24. doi: 10.1007/s12015-023-10575-5.
Jiaqi Chen 1,  Lu Wang 1,  Geng G Tian 2,  Xiang Wang 1,  Xiaoyong Li 3,  Ji Wu 4 5
Affiliations

Affiliations

  • 1 Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
  • 2 Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 3 Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China. xyli@sjtu.edu.cn.
  • 4 Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People's Republic of China. jiwu@sjtu.edu.cn.
  • 5 Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China. jiwu@sjtu.edu.cn.
PMID: 37354386 DOI: 10.1007/s12015-023-10575-5
Abstract

Female germline stem cells (FGSCs) are adult stem cells that can both self-renew and differentiate into mature oocytes. Although small-molecule compounds are capable of regulating the development of FGSCs, the effects and mechanisms of action of metformin, a commonly used drug for diabetes, on FGSCs are largely unknown. Here, we found that metformin promoted the viability and proliferation of FGSCs through H3K27ac modification. To elucidate the mechanism by which metformin promoted FGSCs proliferation, Chromatin Immunoprecipitation Sequencing of histone 3 lysine 27 acetylation (H3K27ac) in FGSCs was performed with or without metformin-treatment. The results indicate that metformin modulates FGSCs via the mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor receptor associated factor 2 (Traf2) was identified as an important target gene for H3K27ac modification during FGSCs proliferation. Subsequent experiments showed metformin promoted FGSCs proliferation by H3K27ac modification of Traf2 to regulate MAPK signaling. Our findings deepen understanding of how H3K27ac modifications regulate FGSCs development and provide a theoretical basis for the prevention and treatment of premature ovarian failure, polycystic ovary syndrome, infertility, and related diseases.

Keywords

Female germline stem cells (FGSCs); Histone acetylation modification; MAPK signal pathway; Metformin; Proliferation.

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