Notch2 deficiency prevents muscle atrophy induced by mechanical unloading and diabetes.

Notch signaling plays essential roles in maintenance of muscle stem cell pool. We found that Notch2, but not Notch1 and Notch3, is expressed in fully differentiated myofibers. To study the specific role of Notch2 in adult myofibers, we generated muscle-specific Notch2-knockout mice. Here, we showed that muscle-specific Notch2 deficiency prevented muscle atrophy induced by hindlimb unloading and diabetes millitus. RNA sequencing analysis revealed that the loss of Notch2 gene in myofibers inhibited gene responses to unloading and diabetes. Especially, several FoxO-target genes and atrogenes were upregulated in wildtype muscles but not in Notch2-deficient muscles by unloading and diabetes. Thus, our characterization of muscle-specific Notch2-knockout mice indicates that Notch2 acts as a regulatory factor of skeletal muscle plasticity and could be a therapeutic target of muscle atrophy. mRNA profiles of gastrocnemius muscle tissues obtained from WT and Notch2-mKO mice under unloading, diabetic, or control condition.Notch信号通路（Notch signaling）在肌肉干细胞池的维持过程中发挥关键作用。本研究发现，Notch2（而非Notch1与Notch3）在完全分化的肌纤维中表达。为探究成年肌纤维中Notch2的特异性生物学功能，我们构建了肌肉特异性Notch2敲除小鼠。本研究结果显示，肌肉特异性Notch2缺失可有效阻断由后肢去负荷与糖尿病诱导的肌肉萎缩。转录组测序（RNA sequencing）分析表明，肌纤维中Notch2基因的缺失可抑制肌纤维对后肢去负荷及糖尿病的基因应答反应。尤其值得注意的是，野生型（wildtype）肌肉中多种FoxO靶基因与肌萎缩基因（atrogenes）可被后肢去负荷与糖尿病诱导上调，而该现象在Notch2缺失型肌肉中并未出现。综上，我们对肌肉特异性Notch2敲除小鼠的表型表征显示，Notch2可作为骨骼肌可塑性的调控因子，同时有望成为肌肉萎缩的治疗靶点。本数据集包含取自野生型（WT）与肌肉特异性Notch2敲除（Notch2-mKO）小鼠腓肠肌（gastrocnemius muscle）组织的mRNA表达谱数据，涵盖后肢去负荷、糖尿病模型及正常对照三种处理条件。