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

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...

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Bibliographic Details
Published in:Stem cell reviews and reports 2023-10, Vol.19 (7), p.2329-2340
Main Authors: Chen, Jiaqi, Wang, Lu, Tian, Geng G., Wang, Xiang, Li, Xiaoyong, Wu, Ji
Format: Article
Language:English
Subjects:
Acetylation
Antidiabetics
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Cell Biology
Cell differentiation
Cell proliferation
Chromatin
Diabetes mellitus
Histones
Immunoprecipitation
Infertility
Kinases
Life Sciences
MAP kinase
Metformin
Oocytes
Polycystic ovary syndrome
Regenerative Medicine/Tissue Engineering
Reproductive status
Signal transduction
Stem Cells
TRAF2 protein
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Summary: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. Graphical Abstract
ISSN:2629-3269
2629-3277
DOI:10.1007/s12015-023-10575-5