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 

机构地区：[1]State Key Laboratory of Reproductive Medicine,Department of Histology and Embryology,Nanjing Medical University,Nanjing,Jiangsu 211166,China

出　　处：《The Journal of Biomedical Research》2021年第1期36-46,I0014-I0016,共14页生物医学研究杂志（英文版）

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)。

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-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 glutaminolysis.Moreover,adding aKG alone to the PGCLC medium accelerated the PGCLC specialization through promoting H3 K27 me3 demethylation.Thus,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.

关 键 词：cellular metabolism Α-KETOGLUTARATE primordial germ cells EPIGENOME 

分 类 号：Q34[生物学—遗传学]