Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease, and it is the most common form of muscular dystrophy caused by genetic mutations in the Dmd gene (1). The Dmd gene contains 79 exons, spans 2.4 Mb, and is the single largest gene in the human genome (2). This gene encodes for dystrophin, which is a component of the dystrophin–glycoprotein complex that provides structural stability to the cell membrane (by connecting the cytoskeleton and the extracellular matrix), and a dysfunctional or absent dystrophin protein leads to progressive muscle wasting with cycles of muscle degeneration and regeneration that ultimately fail (3, 4). Young boys with DMD lose their ability to ambulate, become wheelchair bound, and die prematurely (1, 5). This disease affects skeletal muscle, which is the single largest organ in the body, and it normally has a remarkable capacity for regeneration (6). In response to a severe injury caused by genetic disorders, trauma, or exposure to toxins that destroys over 90% of the muscle, the cytoarchitecture of the injured tissue is completely restored and is indistinguishable compared to uninjured muscle within a 2- to 4-wk period. This regenerative capacity is due to the myogenic stem cell population (i.e., satellite cells) that is resident in adult skeletal muscle, and with repeated DMD-mediated degeneration and regeneration this regenerative process ultimately is exhausted (6). While a number of studies have enhanced our understanding of the myogenic stem cell population, new insights are needed regarding the factors that govern muscle regeneration and potentially serve as therapies for diseases like DMD. In PNAS, Chemello et al. (7) use emerging technologies to provide a discovery science platform. First, they engineered a mouse model by deleting exon 51 of the Dmd gene. This gene-edited mouse (ΔEx51) was viable, lacked dystrophin in skeletal muscle and heart, …

中文翻译：

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使用单核 RNA 测序解码 DMD 转录网络 [细胞生物学]

杜氏肌营养不良症 (DMD) 是一种与 X 染色体相关的疾病，它是由Dmd基因的基因突变引起的最常见的肌营养不良症形式( 1 )。Dmd基因包含 79 个外显子，跨度为 2.4 Mb，是人类基因组中最大的单个基因 ( 2 )。该基因编码肌营养不良蛋白，肌营养不良蛋白是肌营养不良蛋白-糖蛋白复合物的一个组成部分，为细胞膜提供结构稳定性（通过连接细胞骨架和细胞外基质），功能失调或缺乏肌营养不良蛋白导致进行性肌肉萎缩，周期为最终失败的肌肉退化和再生 ( 3 , 4）。患有 DMD 的小男孩失去了行走、坐轮椅和过早死亡的能力 ( 1 , 5 )。这种疾病影响骨骼肌，它是人体最大的器官，通常具有显着的再生能力（6）。为了应对由遗传疾病、创伤或暴露于破坏 90% 以上肌肉的毒素引起的严重损伤，在 2 至 4 周内，与未受伤的肌肉相比，受伤组织的细胞结构完全恢复并且无法区分时期。这种再生能力是由于存在于成年骨骼肌中的成肌干细胞群（即卫星细胞），并且随着 DMD 介导的反复退化和再生，这种再生过程最终会耗尽（6）。虽然许多研究增强了我们对肌源性干细胞群的理解，但对于控制肌肉再生的因素并可能作为 DMD 等疾病的治疗方法，还需要新的见解。在 PNAS 中，Chemello 等人。( 7) 使用新兴技术提供发现科学平台。首先，他们通过删除Dmd基因的外显子 51 设计了一个小鼠模型。这种基因编辑的小鼠 (ΔEx51) 是可行的，骨骼肌和心脏中缺乏肌营养不良蛋白，……