ArticleJournal of biomedical research2020
α-ketoglutarate promotes the specialization of primordial germ cell-like cells through regulating epigenetic reprogramming.
Article in Journal of biomedical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Characterization of the metabolome and proteome of stem cell-derived human primordial germ cell-like cells: a multi-omics approach.Biology open · 2026Article
- Integrated metabolomic and transcriptomic analyses reveal that glutamine promotes chicken primordial germ cell‑like cell specification potentially through α-ketoglutarate.Animal bioscience · 2026Article
- A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation.Reproduction (Cambridge, England) · 2024Article
- Metabolic-epigenetic nexus in regulation of stem cell fate.World journal of stem cells · 2022Review
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- Metabolic pathways regulating the development and non-genomic heritable traits of germ cells.The Journal of reproduction and development · 2022Review
- Metabolic Control of Germline Formation and Differentiation in Mammals.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2022Review
Corrections and comments
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Authors and funding
4 authors.
Funding
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Abstract
There is growing evidence that cellular metabolism can directly participate in epigenetic dynamics and consequently modulate gene expression. However, the role of metabolites in activating the key gene regulatory network for specialization of germ cell lineage remains largely unknown. Here, we identified some cellular metabolites with significant changes by untargeted metabolomics between mouse epiblast-like cells (EpiLCs) and primordial germ cell-like cells (PGCLCs). More importantly, we found that inhibition of glutaminolysis by bis-2- (5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) impeded PGCLC specialization, but the impediment could be rescued by addition of α-ketoglutarate (αKG), the intermediate metabolite of oxidative phosphorylation and glutaminolysis. Moreover, adding αKG alone to the PGCLC medium accelerated the PGCLC specialization through promoting H3K27me3 demethylation. Thus, our study reveals the importance of metabolite αKG in the germ cell fate determination and highlights the essential role of cellular metabolism in shaping the cell identities through epigenetic events.
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