Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.
Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.
Curr Top Dev Biol. 2018;126:235-284. doi: 10.1016/bs.ctdb.2017.08.002. Epub 2017 Sep 28.
Skeletal muscle regeneration is an efficient stem cell-based repair system that ensures healthy musculature. For this repair system to function continuously throughout life, muscle stem cells must contribute to the process of myofiber repair as well as repopulation of the stem cell niche. The decision made by the muscle stem cells to commit to the muscle repair or to remain a stem cell depends upon patterns of gene expression, a process regulated at the epigenetic level. Indeed, it is well accepted that dynamic changes in epigenetic landscapes to control DNA accessibility and expression is a critical component during myogenesis for the effective repair of damaged muscle. Changes in the epigenetic landscape are governed by various posttranslational histone tail modifications, nucleosome repositioning, and DNA methylation events which collectively allow the control of changes in transcription networks during transitions of satellite cells from a dormant quiescent state toward terminal differentiation. This chapter focuses upon the specific epigenetic changes that occur during muscle stem cell-mediated regeneration to ensure myofiber repair and continuity of the stem cell compartment. Furthermore, we explore open questions in the field that are expected to be important areas of exploration as we move toward a more thorough understanding of the epigenetic mechanism regulating muscle regeneration.
骨骼肌再生是一种高效的基于干细胞的修复系统,可确保肌肉组织的健康。为了使该修复系统能够在整个生命周期内持续发挥作用,肌肉干细胞必须参与肌纤维修复以及干细胞龛的再填充过程。肌肉干细胞决定是致力于肌肉修复还是保持干细胞状态,取决于基因表达模式,这一过程受表观遗传水平的调控。实际上,人们普遍认为,在肌发生过程中,通过表观遗传景观的动态变化来控制 DNA 的可及性和表达,是有效修复受损肌肉的关键组成部分。表观遗传景观的变化受各种翻译后组蛋白尾部修饰、核小体重定位和 DNA 甲基化事件的控制,这些事件共同允许在卫星细胞从休眠静止状态向终末分化的过渡过程中,控制转录网络的变化。本章重点介绍了在肌肉干细胞介导的再生过程中发生的特定表观遗传变化,以确保肌纤维修复和干细胞隔室的连续性。此外,我们还探讨了该领域的开放性问题,这些问题有望成为我们深入了解调节肌肉再生的表观遗传机制的重要探索领域。