Loss of full-length dystrophin expression causes major cell-autonomous abnormalities in proliferating myoblasts

Duchenne muscular dystrophy (DMD) is a severely debilitating and incurable neuromuscular disease. Its conspicuous feature is the absence of dystrophin in myofibers and therefore most therapeutic approaches focus on some form of its re-expression there. However, increasing body of evidence points at an early developmental onset of DMD and severe abnormalities were uncovered in dystrophic muscle stem cells. In this study, we explore gene expression changes in primary myoblasts from mice lacking expression of the full length dystrophin transcript. Total RNA extracted from primary myoblasts isolated from gastrocnemii of 8 week old male Dmd-mdx (MDX - lacking the full length dystrophin transcript), Dmd-mdx-betageo (BGEO - lacking all dystrophin expression) and control mice (WT) were subjected to RNA sequencing following ribodepletion, and analysed for the differential expression of genes between groups and the enrichment of gene ontology categories or pathways.杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）是一种严重致残且无法治愈的神经肌肉疾病。其核心显著特征为肌纤维内肌营养不良蛋白（dystrophin）的缺失，因此绝大多数治疗策略均围绕在肌纤维中重新表达该蛋白展开。然而，日益增多的证据表明DMD的发病始于发育早期，且肌营养不良性肌肉干细胞存在严重异常。本研究针对全长肌营养不良蛋白转录本缺失的小鼠原代成肌细胞（primary myoblasts），探究其基因表达变化。研究人员从8周龄雄性Dmd-mdx（MDX——缺失全长肌营养不良蛋白转录本）、Dmd-mdx-betageo（BGEO——缺失所有肌营养不良蛋白表达）及野生型（wild type, WT）小鼠的腓肠肌（gastrocnemii）中分离原代成肌细胞，提取总RNA后经核糖体去除（ribodepletion）处理，随后开展RNA测序（RNA sequencing），并分析各组间基因的差异表达情况，以及基因本体论（Gene Ontology, GO）类别或通路的富集程度。