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

作     者：Ming Xing Na Wang Hanyi Zeng Jun Zhang Ming Xing;Na Wang;Hanyi Zeng;Jun Zhang

作者机构：State Key Laboratory of Reproductive MedicineDepartment of Histology and EmbryologyNanjing Medical UniversityNanjingJiangsu 211166China 

出 版 物：《The Journal of Biomedical Research》 (生物医学研究杂志（英文版）)

年 卷 期：2021年第35卷第1期

页      面：36-46,I0014-I0016页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：supported by grants from the National Natural Science Foundation of China(No.31871445 and No.31501211) the National Key R&D program of China(No.2017YFC1001302 and No.2016YFA0503300) 

主　　题：cellular metabolism α-ketoglutarate primordial germ cells epigenome 

摘      要：There is growing evidence that cellular metabolism can directly participate in epigenetic dynamics and consequently modulate gene ***,the role of metabolites in activating the key gene regulatory network for specialization of germ cell lineage remains largely ***,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 ofα-ketoglutarate(αKG),the intermediate metabolite of oxidative phosphorylation and ***,adding aKG alone to the PGCLC medium accelerated the PGCLC specialization through promoting H3 K27 me3 ***,our study reveals the importance of metabolite aKG in the germ cell fate determination and highlights the essential role of cellular metabolism in shaping the cell identities through epigenetic events.