DNA maintenance methylation enzyme Dnmt1 in satellite cells is essential for muscle regeneration

被引:8
|
作者
Iio, Hiroyuki [1 ,2 ]
Kikugawa, Tadahiko [1 ]
Sawada, Yuichiro [1 ,2 ]
Sakai, Hiroshi [2 ,3 ]
Yoshida, Shuhei [3 ]
Yanagihara, Yuta [2 ,4 ]
Ikedo, Aoi [2 ]
Saeki, Noritaka [2 ,4 ]
Fukada, So-ichiro [5 ]
Saika, Takashi [1 ]
Imai, Yuuki [2 ,3 ,4 ]
机构
[1] Ehime Univ, Grad Sch Med, Dept Urol, Shitsukawa, Toon Ehime 7910295, Japan
[2] Ehime Univ, Div Integrat Pathophysiol, Proteosci Ctr, Shitsukawa, Toon Ehime 7910295, Japan
[3] Ehime Univ, Dept Pathophysiol, Grad Sch Med, Shitsukawa, Toon Ehime 7910295, Japan
[4] Ehime Univ, Div Lab Anim Res, Adv Res Support Ctr, Shitsukawa, Toon Ehime 7910295, Japan
[5] Osaka Univ, Grad Sch Pharmaceut Sci, Project Muscle Stem Cell Biol, Suita, Osaka 5650871, Japan
基金
日本学术振兴会;
关键词
Dnmt1; DNA methylation; Epigenetics; Skeletal muscle; Muscle satellite cells; Muscle regeneration; STEM-CELLS; HYPERTROPHY; PAX7;
D O I
10.1016/j.bbrc.2020.11.116
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epigenetic transcriptional regulation is essential for the differentiation of various types of cells, including skeletal muscle cells. DNA methyltransferase 1 (Dnmt1) is responsible for maintenance of DNA methylation patterns via cell division. Here, we investigated the relationship between Dnmt1 and skeletal muscle regeneration. We found that Dnmt1 is upregulated in muscles during regeneration. To assess the role of Dnmtl in satellite cells during regeneration, we performed conditional knockout (cKO) of Dnmt1 specifically in skeletal muscle satellite cells using Pax7(CreERT2) mice and Dnmt1 flox mice. Muscle weight and the cross-sectional area after injury were significantly lower in Dnmt1 cKO mice than in control mice. RNA sequencing analysis revealed upregulation of genes involved in cell adhesion and apoptosis in satellite cells from cKO mice. Moreover, satellite cells cultured from cKO mice exhibited a reduced number of cells. These results suggest that Dnmt1 is an essential factor for muscle regeneration and is involved in positive regulation of satellite cell number. (C)2020 Elsevier Inc. All rights reserved.
引用
收藏
页码:79 / 85
页数:7
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