Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Anatomy, Cell Biology, and Physiology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
Int J Mol Sci. 2023 Aug 5;24(15):12463. doi: 10.3390/ijms241512463.
The gene is responsible for Duchenne muscular dystrophy (DMD), a grave X-linked recessive ailment that results in respiratory and cardiac failure. As the expression of in muscle stem cells (MuSCs) is a topic of debate, there exists a limited understanding of its influence on the gene network of MuSCs. This study was conducted with the objective of investigating the effects of on the regulatory network of genes in MuSCs. To comprehend the function of in MuSCs from DMD, this investigation employed single-nuclei RNA sequencing (snRNA-seq) to appraise the transcriptomic profile of MuSCs obtained from the skeletal muscles of mutant mice () and wild-type control mice. The study revealed that the mutation caused the disruption of several long non-coding RNAs (lncRNAs), leading to the inhibition of MEG3 and NEAT1 and the upregulation of GM48099, GM19951, and GM15564. The Gene Ontology (GO) enrichment analysis of biological processes (BP) indicated that the mutation activated the cell adhesion pathway in MuSCs, inhibited the circulatory system process, and affected the regulation of binding. The study also revealed that the metabolic pathway activity of MuSCs was altered. The metabolic activities of oxidative phosphorylation (OXPHOS) and glycolysis were elevated in MuSCs from . In summary, this research offers novel insights into the disrupted gene regulatory program in MuSCs due to mutation at the single-cell level.
该基因负责杜氏肌营养不良症（DMD），一种严重的 X 连锁隐性疾病，导致呼吸和心脏衰竭。由于 在肌肉干细胞（MuSCs）中的表达存在争议，因此对其对 MuSCs 基因网络的影响的了解有限。本研究旨在研究 对 MuSCs 基因调控网络的影响。为了从 DMD 中理解 在 MuSCs 中的功能，该研究使用单核 RNA 测序（snRNA-seq）评估了从 突变型（）和野生型对照小鼠的骨骼肌中获得的 MuSCs 的转录组谱。研究表明， 突变导致几个长非编码 RNA（lncRNA）的破坏，导致 MEG3 和 NEAT1 的抑制以及 GM48099、GM19951 和 GM15564 的上调。生物过程（BP）的基因本体论（GO）富集分析表明， 在 MuSCs 中激活了细胞黏附途径，抑制了循环系统过程，并影响了结合的调节。该研究还表明 MuSCs 的代谢途径活性发生了改变。 的 MuSCs 中的氧化磷酸化（OXPHOS）和糖酵解代谢活性升高。总之，这项研究在单细胞水平上提供了关于 突变导致 MuSCs 中基因调控程序中断的新见解。
