Transcriptional and Chromatin Dynamics of Muscle Regneration after Severe Trauma

Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that control these reparative events is lacking. To address this, we monitored the in vivo dynamics of three histone modifications and coding and noncoding RNA expression throughout the regenerative process in a mouse model of traumatic muscle injury. We first illustrate how both coding and noncoding RNAs in tissues and sorted satellite cells are modified and regulated during various stages after trauma. Next, we use chromatin immunoprecipitation followed by sequencing to evaluate the chromatin state of cis-regulatory elements (promoters and enhancers) and view how these elements evolve and influence various muscle repair and regeneration transcriptional programs. These results provide a comprehensive view of the central factors that regulate muscle regeneration and underscore the multiple levels through which both transcriptional and epigenetic patterns are regulated to enact appropriate repair and regeneration. ChIP-Seq time course of muscle injury healing with controls RNA-Seq time course of muscle satellite cells following injury healing miRNA-seq time course of muscle satellite cells following injury healing

成年骨骼肌在遭受损伤后，会启动一系列高度协调的分子与生理学事件，以推进损伤修复与再生进程。然而，目前学界对调控这类修复事件的体内表观基因组学与转录调控机制仍缺乏全面深入的认知。为填补这一研究空白，本研究在创伤性肌肉损伤的小鼠模型中，追踪了整个再生过程中三种组蛋白修饰的体内动态变化，以及编码RNA与非编码RNA的表达水平。我们首先阐明了创伤后不同阶段，组织与分选得到的肌卫星细胞（satellite cells）中编码RNA与非编码RNA的修饰与调控模式。随后，我们采用染色质免疫共沉淀测序（ChIP-Seq）技术，评估顺式调控元件（启动子与增强子）的染色质状态，并解析这类元件如何动态变化并调控各类肌肉修复与再生相关的转录程序。本研究结果全面揭示了调控肌肉再生的核心因子，并阐明了转录与表观遗传模式通过多层级调控机制，以实现精准的损伤修复与再生。本研究涵盖三类时间序列数据集：带对照组的肌肉损伤愈合ChIP-Seq时间序列数据集、损伤愈合后肌卫星细胞的RNA-Seq时间序列数据集，以及损伤愈合后肌卫星细胞的miRNA-seq时间序列数据集。