Uhrf1 governs the proliferation and differentiation of muscle satellite cells.
Uhrf1 governs the proliferation and differentiation of muscle satellite cells.
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Uhrf1调控肌卫星细胞的增殖和分化。
DOI：
10.1016/j.isci.2022.103928
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发表时间：
2022-03-18
期刊：
影响因子：
5.8
通讯作者：
Imai Y
中科院分区：
文献类型：
--
作者：
Sakai H;Sawada Y;Tokunaga N;Tanaka K;Nakagawa S;Sakakibara I;Ono Y;Fukada SI;Ohkawa Y;Kikugawa T;Saika T;Imai Y
DNA甲基化是表观遗传调控的重要形式，负责细胞的身份。在肌肉干细胞中，称为卫星细胞，DNA甲基化模式在分化过程中受到严格调控。然而，目前还不清楚这些DNA甲基化模式如何影响卫星细胞的功能。我们证明，一个关键的表观遗传调节，泛素样与PHD和环指结构域1（Uhrf 1），在增殖的肌源性细胞中被激活，但在静止的卫星细胞或分化的肌源性细胞在小鼠中不表达。小鼠卫星细胞中Uhrf 1的消融损害了它们的增殖和分化，导致肌肉再生失败。Uhrf 1缺陷的肌原细胞表现出异常上调的成绩单，包括Sox 9，其启动子和增强子区域的DNA甲基化水平的降低。这些发现表明，Uhrf 1是卫星细胞增殖和分化的关键表观遗传调节因子，通过维持DNA甲基化控制细胞类型特异性基因表达。Uhrf 1在增殖的肌原细胞中被激活Uhrf 1在卫星细胞中是肌肉再生所必需的Uhrf 1在卫星细胞中的消融损害它们的增殖和分化Uhrf 1通过维持DNA甲基化控制细胞类型特异性转录本表观遗传学;细胞生物学;干细胞研究
DNA methylation is an essential form of epigenetic regulation responsible for cellular identity. In muscle stem cells, termed satellite cells, DNA methylation patterns are tightly regulated during differentiation. However, it is unclear how these DNA methylation patterns affect the function of satellite cells. We demonstrate that a key epigenetic regulator, ubiquitin like with PHD and RING finger domains 1 (Uhrf1), is activated in proliferating myogenic cells but not expressed in quiescent satellite cells or differentiated myogenic cells in mice. Ablation of Uhrf1 in mouse satellite cells impairs their proliferation and differentiation, leading to failed muscle regeneration. Uhrf1-deficient myogenic cells exhibited aberrant upregulation of transcripts, including Sox9, with the reduction of DNA methylation level of their promoter and enhancer region. These findings show that Uhrf1 is a critical epigenetic regulator of proliferation and differentiation in satellite cells, by controlling cell-type-specific gene expression via maintenance of DNA methylation. Uhrf1 is activated in proliferating myogenic cells Uhrf1 in satellite cells is required for muscle regeneration Ablation of Uhrf1 in satellite cells impairs their proliferation and differentiation Uhrf1 controls cell-type-specific transcripts via maintenance of DNA methylation Epigenetics; Cell biology; Stem cells research
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