多梳抑制酶 EZH2 控制着骨骼肌干细胞的自我更新和转录特性。
Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells.
机构信息
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland 20892, USA.
出版信息
Genes Dev. 2011 Apr 15;25(8):789-94. doi: 10.1101/gad.2027911.
Abstract
Satellite cells (SCs) sustain muscle growth and empower adult skeletal muscle with vigorous regenerative abilities. Here, we report that EZH2, the enzymatic subunit of the Polycomb-repressive complex 2 (PRC2), is expressed in both Pax7+/Myf5⁻ stem cells and Pax7+/Myf5+ committed myogenic precursors and is required for homeostasis of the adult SC pool. Mice with conditional ablation of Ezh2 in SCs have fewer muscle postnatal Pax7+ cells and reduced muscle mass and fail to appropriately regenerate. These defects are associated with impaired SC proliferation and derepression of genes expressed in nonmuscle cell lineages. Thus, EZH2 controls self-renewal and proliferation, and maintains an appropriate transcriptional program in SCs.
摘要
卫星细胞（SCs）维持肌肉生长，并赋予成年骨骼肌强大的再生能力。在这里，我们报告说，EZH2 是 Polycomb-repressive complex 2（PRC2）的酶亚基，在 Pax7+/Myf5⁻干细胞和 Pax7+/Myf5+ 定向成肌前体细胞中均有表达，对于成体 SC 池的稳态是必需的。在 SC 中条件性缺失 Ezh2 的小鼠，其肌肉 Pax7+细胞较少，肌肉质量降低，且无法适当再生。这些缺陷与 SC 增殖受损和非肌肉细胞谱系中表达的基因去抑制有关。因此，EZH2 控制自我更新和增殖，并维持 SC 中适当的转录程序。
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