α-ketoglutarate promotes the specialization of primordial germ cell-like cells through regulating epigenetic reprogramming
Ming Xing
Na Wang
Hanyi Zeng
Jun Zhang
1.State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Naning Medical University, Nanjing, Jiangsu 211166, China2.State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Naning Medical University, Nanjing, Jiangsu 211166, China3.State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Naning Medical University, Nanjing, Jiangsu 211166, China4.State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Naning Medical University, Nanjing, Jiangsu 211166, China
摘要：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.
机标关键词：
分类号：Q34(遗传学分支学科)
资助基金：This work was supported by grants from the National Natural Science Foundation of China (No.31871445 and No.31501211)and the National Key R&D program of China (No.2017YFC1001302 and No.2016YFA0503300)
论文发表日期：2021-01-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 36-46 )
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