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

Xing Ming; Wang Na; Zeng Hanyi; Zhang Jun

doi:10.7555/JBR.34.20190160

Volume 35 Issue 1

Jan. 2021

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Xing Ming, Wang Na, Zeng Hanyi, Zhang Jun. α-ketoglutarate promotes the specialization of primordial germ cell-like cells through regulating epigenetic reprogramming[J]. The Journal of Biomedical Research, 2021, 35(1): 36-46. doi: 10.7555/JBR.34.20190160

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Xing Ming, Wang Na, Zeng Hanyi, Zhang Jun. α-ketoglutarate promotes the specialization of primordial germ cell-like cells through regulating epigenetic reprogramming[J]. The Journal of Biomedical Research, 2021, 35(1): 36-46. doi: 10.7555/JBR.34.20190160

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

doi: 10.7555/JBR.34.20190160

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 211166, China

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Corresponding author: Jun Zhang, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, China. Tel: +86-25-86869381, E-mail: zhang_jun@njmu.edu.cn
Received: 2019-12-26
Revised: 2020-05-20
Accepted: 2020-06-05

Published: 2020-08-06

Issue Date: 2021-01-28

Abstract

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.
- cellular metabolism,
- α-ketoglutarate,
- primordial germ cells,
- epigenome

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References(35)

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