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World J Stem Cells. Jul 26, 2022; 14(7): 490-502
Published online Jul 26, 2022. doi: 10.4252/wjsc.v14.i7.490
Metabolic-epigenetic nexus in regulation of stem cell fate
Yi Liu, Di-Xin Cui, Yue Pan, Si-Han Yu, Li-Wei Zheng, Mian Wan
Yi Liu, Di-Xin Cui, Yue Pan, Si-Han Yu, Li-Wei Zheng, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Mian Wan, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Liu Y and Wan M conceived and designed the study; Cui DX, Pan Y and Yu SH collected materials; Liu Y wrote the paper; Zheng LW and Wan M revised the manuscript critically; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China (General Program), No. 82170921; the Sichuan Science and Technology Program, No. 2022YFS0284; and the Research and Develop Program, West China Hospital of Stomatology Sichuan University, No. LCYJ2019-24.
Conflict-of-interest statement: The authors declare that there is no conflict of interests regarding the publication of this paper.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mian Wan, DDS, PhD, Academic Research, Attending Doctor, Lecturer, Postdoctoral Fellow, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, No. 14 People's South Road, Chengdu 610041, Sichuan Province, China. mianwan@scu.edu.cn
Received: March 18, 2022
Peer-review started: March 18, 2022
First decision: April 25, 2022
Revised: May 31, 2022
Accepted: July 8, 2022
Article in press: July 8, 2022
Published online: July 26, 2022
Processing time: 129 Days and 17.1 Hours
Abstract

Stem cell fate determination is one of the central questions in stem cell biology, and although its regulation has been studied at genomic and proteomic levels, a variety of biological activities in cells occur at the metabolic level. Metabolomics studies have established the metabolome during stem cell differentiation and have revealed the role of metabolites in stem cell fate determination. While metabolism is considered to play a biological regulatory role as an energy source, recent studies have suggested the nexus between metabolism and epigenetics because several metabolites function as cofactors and substrates in epigenetic mechanisms, including histone modification, DNA methylation, and microRNAs. Additionally, the epigenetic modification is sensitive to the dynamic metabolites and consequently leads to changes in transcription. The nexus between metabolism and epigenetics proposes a novel stem cell-based therapeutic strategy through manipulating metabolites. In the present review, we summarize the possible nexus between metabolic and epigenetic regulation in stem cell fate determination, and discuss the potential preventive and therapeutic strategies via targeting metabolites.

Keywords: Metabolism; Epigenetic regulation; Stem cell fate; Nexus effect

Core Tip: Stem cell fate can be regulated by metabolites. Recent studies have suggested that there is a nexus between metabolism and epigenetics, as several metabolites could function as cofactors and substrates in epigenetic mechanisms. We review many basic and preclinical studies, and the results support this view. This finding may provide a clue to further studies on the co-effects of metabolism and epigenetics in cell fate determination.