DNA maintenance methylation enzyme Dnmt1 in satellite cells is essential for muscle regeneration
DNA maintenance methylation enzyme Dnmt1 in satellite cells is essential for muscle regeneration
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DOI：
10.1016/j.bbrc.2020.11.116
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Imai, Yuuki
中科院分区：
文献类型：
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作者：
Iio, Hiroyuki;Kikugawa, Tadahiko;Imai, Yuuki
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是必不可少的。DNA甲基转移酶1（Dnmt 1）负责通过细胞分裂维持DNA甲基化模式。在这里，我们研究了Dnmt 1和骨骼肌再生之间的关系。我们发现Dnmt 1在肌肉再生过程中上调。为了评估Dnmtl在再生过程中在卫星细胞中的作用，我们使用Pax7（CreERT2）小鼠和Dnmtl flox小鼠在骨骼肌卫星细胞中特异性地进行了Dnmtl的条件性敲除（cKO）。Dnmt 1 cKO小鼠的肌肉重量和损伤后的横截面积显著低于对照小鼠。RNA测序分析显示cKO小鼠卫星细胞中参与细胞粘附和凋亡的基因上调。此外，从cKO小鼠培养的卫星细胞表现出细胞数量减少。这些结果表明，Dnmt 1是肌肉再生的一个重要因素，并参与卫星细胞数量的正调控。（C）2020 Elsevier Inc. All rights reserved.
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.