Transcriptomic data and analyses of shMeg3 muscle in vitro and in vivo

Formation of skeletal muscle is among the most striking examples of cellular plasticity in animal tissue development, and while muscle progenitor cells are reprogrammed by epithelial-mesenchymal transition (EMT) to migrate during embryonic development, regulation of EMT in postnatal myogenesis remains poorly understood. Here, we demonstrate that the long noncoding RNA (lncRNA) Meg3 regulates EMT in myoblast differentiation and skeletal muscle regeneration. Chronic inhibition of Meg3 in C2C12 myoblasts induced EMT, and supressed cell state transitions required for differentiation. Furtheremore, adenoviral Meg3 knockdown compromised muscle regeneration, which was accompanied by abnormal mesenchymal gene expression and interstitial cell proliferation. Transcriptomic and pathway analyses of Meg3-depleted C2C12 myoblasts and injured skeletal muscle revealed a significant dysregulation of EMT-related genes, and identified TGFβ as a key upstream regulator. Importantly, inhibition of TGFβR1 and...

骨骼肌形成是动物组织发育过程中最具代表性的细胞可塑性（cellular plasticity）案例之一。尽管胚胎发育阶段的肌肉祖细胞可通过上皮间质转化（Epithelial-Mesenchymal Transition, EMT）发生重编程以实现迁移，但产后肌发生过程中EMT的调控机制仍有待阐明。本研究证实，长链非编码RNA（long noncoding RNA, lncRNA）Meg3可调控成肌细胞分化与骨骼肌再生过程中的EMT进程。在C2C12成肌细胞中长期抑制Meg3表达可诱导EMT发生，并阻断分化所需的细胞状态转换。此外，腺病毒介导的Meg3敲低会损害肌肉再生能力，同时伴随异常的间质基因表达与间质细胞增殖。对Meg3缺失的C2C12成肌细胞及受损骨骼肌开展的转录组学与通路分析显示，EMT相关基因存在显著表达失调，并鉴定出转化生长因子β（TGFβ）为关键上游调控因子。重要的是，抑制转化生长因子β受体1（TGFβR1）并……