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World J Stem Cells. May 26, 2020; 12(5): 351-358
Published online May 26, 2020. doi: 10.4252/wjsc.v12.i5.351
DNA methylation and demethylation link the properties of mesenchymal stem cells: Regeneration and immunomodulation
Tian-Yi Xin, Ting-Ting Yu, Rui-Li Yang
Tian-Yi Xin, Ting-Ting Yu, Rui-Li Yang, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
Author contributions: Xin TY and Yu TT collected the data and wrote the manuscript; Yang RL critically revised the manuscript; all authors read and approved the manuscript.
Supported by Beijing Natural Science Foundation, No. 7182182; the Young Elite Scientist Sponsorship Program by Cast, No. YESS20170089; the National Natural Science Foundation of China, No. 81600865 and No. 81970940; and the National Science and Technology Major Project of the Ministry of Science and Technology of China, No. 2018ZX10302207.
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Rui-Li Yang, DDS, PhD, Assistant Professor, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, No. 22, Zhongguancun South Avenue, Beijing 100081, China. ruiliyangabc@163.com
Received: January 12, 2020
Peer-review started: January 12, 2020
First decision: February 25, 2020
Revised: March 27, 2020
Accepted: April 24, 2020
Article in press: April 24, 2020
Published online: May 26, 2020
Processing time: 135 Days and 10.5 Hours
Abstract

Mesenchymal stem cells (MSCs) are a heterogeneous population that can be isolated from various tissues, including bone marrow, adipose tissue, umbilical cord blood, and craniofacial tissue. MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation. The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types. In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases. DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance, proliferation, differentiation and apoptosis by activating or suppressing a number of genes. In most studies, DNA hypermethylation is associated with gene suppression, while hypomethylation or demethylation is associated with gene activation. The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes. However, the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation. In this review, we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work. Furthermore, we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.

Keywords: Mesenchymal stem cells; DNA methylation and demethylation; Multi-lineage differentiation; Regeneration; Immunomodulation; Immune disease

Core tip: Mesenchymal stem cells (MSCs) harbor the capacity to regenerate diverse tissues and can also perform key immunomodulatory functions. DNA methylation and demethylation are known to modulate stem cell maintenance and differentiation in embryonic stem cells. However, the role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation. In this review, we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work. In addition, we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.