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通过表观遗传机制调节骨骼肌干细胞。

Regulation of skeletal muscle stem cells through epigenetic mechanisms.

机构信息

Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), Barcelona, Spain.

出版信息

Toxicol Mech Methods. 2011 May;21(4):334-42. doi: 10.3109/15376516.2011.557873.

Abstract

Quiescent adult skeletal muscle stem cells (satellite cells) are the main players of myogenesis assuring the possibility of growth and regeneration of the muscle tissue throughout adult life. The environmental stimuli that activate satellite cells induce their proliferation, leading on one hand to self-renewal and maintenance of the muscle stem cell reservoir, and on the other hand to the production of progenitor cells that further proliferate, differentiate, and fuse to form new muscle fibers. Hence, satellite cells constitute a perfect system to study the transitions involved in stem cell differentiation. The multistep process of myogenesis is orchestrated by specific regulatory proteins, such as Pax3/Pax7 or members of the MyoD family of transcription factors. However, findings published over the past few years indicate that epigenetic mechanisms, such as covalent modification of histones, DNA methylation, or regulation of gene expression by microRNAs, also critically repress, maintain, or induce the muscle-specific transcriptional program during myogenesis. These studies have increased our understanding of how the information encoding the muscle lineage is molecularly controlled.

摘要

静息状态的成年骨骼肌干细胞(卫星细胞)是肌发生的主要参与者,保证了肌肉组织在整个成年期生长和再生的可能性。激活卫星细胞的环境刺激诱导其增殖,一方面导致肌肉干细胞库的自我更新和维持,另一方面导致祖细胞的产生,这些祖细胞进一步增殖、分化并融合形成新的肌肉纤维。因此,卫星细胞构成了研究干细胞分化所涉及的转变的完美系统。肌发生的多步过程由特定的调节蛋白协调,例如 Pax3/Pax7 或 MyoD 家族转录因子的成员。然而,过去几年发表的研究结果表明,表观遗传机制,如组蛋白的共价修饰、DNA 甲基化或 microRNAs 对基因表达的调节,也在肌发生过程中严格抑制、维持或诱导肌肉特异性转录程序。这些研究增加了我们对肌肉谱系信息如何在分子水平上受到控制的理解。

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