Iio Hiroyuki, Kikugawa Tadahiko, Sawada Yuichiro, Sakai Hiroshi, Yoshida Shuhei, Yanagihara Yuta, Ikedo Aoi, Saeki Noritaka, Fukada So-Ichiro, Saika Takashi, Imai Yuuki
Department of Urology, Ehime University Graduate School of Medicine, Shitsukawa, Toon Ehime, 791-0295, Japan; Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Shitsukawa, Toon Ehime, 791-0295, Japan.
Department of Urology, Ehime University Graduate School of Medicine, Shitsukawa, Toon Ehime, 791-0295, Japan.
Biochem Biophys Res Commun. 2021 Jan 1;534:79-85. doi: 10.1016/j.bbrc.2020.11.116. Epub 2020 Dec 10.
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 Dnmt1 in satellite cells during regeneration, we performed conditional knockout (cKO) of Dnmt1 specifically in skeletal muscle satellite cells using Pax7 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.
表观遗传转录调控对于包括骨骼肌细胞在内的各种类型细胞的分化至关重要。DNA甲基转移酶1(Dnmt1)负责通过细胞分裂维持DNA甲基化模式。在此,我们研究了Dnmt1与骨骼肌再生之间的关系。我们发现Dnmt1在再生过程中的肌肉中上调。为了评估Dnmt1在再生过程中卫星细胞中的作用,我们使用Pax7小鼠和Dnmt1基因敲除小鼠在骨骼肌卫星细胞中特异性地进行了Dnmt1的条件性敲除(cKO)。Dnmt1基因敲除小鼠损伤后的肌肉重量和横截面积显著低于对照小鼠。RNA测序分析显示,基因敲除小鼠卫星细胞中参与细胞黏附和凋亡的基因上调。此外,从基因敲除小鼠培养的卫星细胞数量减少。这些结果表明,Dnmt1是肌肉再生的关键因素,并参与卫星细胞数量的正向调控。