α-ketoglutarate promotes the specialization of primordial germ cell-like cells through regulating ep

• 作 者: Ming Xing Na Wang Hanyi Zeng Jun Zhang
• 机 构: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Naning Medica
• 出 处: 生物医学研究杂志（英文版）
• 发表日期: 2021年1期
• 关键词: cellular metabolism α-ketoglutarate primordial germ cells epigenome

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-l,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 metaboliteαKG in the germ cell fate determination and highlights the essential role of cellular metabolism in shaping the cell identities through epigenetic events.