ArticleStem cell research & therapy2023
Metformin promotes female germline stem cell proliferation by upregulating Gata-binding protein 2 with histone β-hydroxybutyrylation.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- CHIR99021 Enhances the Proliferation of Mouse Female Germline Stem Cells Via Modulating ERCC2.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- H3K18 lactylation-mediated Ythdf2 activation restrains mouse female germline stem cell proliferation via promoting Ets1 mRNA degradation.Clinical epigenetics · 2025Article
- Ketogenic diet and β-hydroxybutyrate in osteoporosis: current progress and controversy.Frontiers in nutrition · 2025Review
- From ketogenic metabolism to targeted therapeutics: current advances in β-hydroxybutyrylation.Frontiers in immunology · 2025Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin as a first-line clinical anti-diabetic agent prolongs the lifespan of model animals and promotes cell proliferation. However, the molecular mechanisms underlying the proliferative phenotype, especially in epigenetics, have rarely been reported. The aim of this study was to investigate the physiological effects of metformin on female germline stem cells (FGSCs) in vivo and in vitro, uncover β-hydroxybutyrylation epigenetic modification roles of metformin and identify the mechanism of histone H2B Lys5 β-hydroxybutyrylation (H2BK5bhb) in Gata-binding protein 2 (Gata2)-mediated proliferation promotion of FGSCs.
methodsThe physiological effects of metformin were evaluated by intraperitoneal injection and histomorphology. The phenotype and mechanism studies were explored by cell counting, cell viability, cell proliferation assay and protein modification omics, transcriptomics, chromatin immunoprecipitation sequencing in FGSCs in vitro.
resultsWe found that metformin treatment increased the number of FGSCs, promoted follicular development in mouse ovaries and enhanced the proliferative activity of FGSCs in vitro. Quantitative omics analysis of protein modifications revealed that H2BK5bhb was increased after metformin treatment of FGSCs. In combination with H2BK5bhb chromatin immunoprecipitation and transcriptome sequencing, we found that Gata2 might be a target gene for metformin to regulate FGSC development. Subsequent experiments showed that Gata2 promoted FGSC proliferation.
conclusionOur results provide novel mechanistic understanding of metformin in FGSCs by combining histone epigenetics and phenotypic analyses, which highlight the role of the metformin-H2BK5bhb-Gata2 pathway in cell fate determination and regulation.
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