Dystrophin deficiency impairs cell junction formation during embryonic myogenesis.
Dystrophin deficiency impairs cell junction formation during embryonic myogenesis.
复制标题
肌营养不良蛋白缺乏会损害胚胎肌发生过程中的细胞连接形成。
DOI：
10.1101/2023.12.05.569919
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Dupont,Jean-Baptist
中科院分区：
文献类型：
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作者：
Mozin,Elise;Massouridès,Emmanuelle;Mournetas,Virginie;Lièvre,Clémence;Bourdon,Audrey;Jackson,DanaL;Packer,JonathanS;Seong,Juyoung;Trapnell,Cole;LeGuiner,Caroline;Adjali,Oumeya;Pinset,Christian;Mack,DavidL;Dupont,Jean-Baptist
Mutations in the DMD gene lead to Duchenne muscular dystrophy, a severe X-linked neuromuscular disorder that manifests itself as young boys acquire motor functions. DMD is typically diagnosed at 2 to 4 years of age, but the absence of dystrophin negatively impacts muscle structure and function before overt symptoms appear in patients, which poses a serious challenge in the optimization of standards of care. In this report, we investigated the early consequences of dystrophin deficiency during skeletal muscle development. We used single-cell transcriptome profiling to characterize the myogenic trajectory of human pluripotent stem cells and showed that DMD cells bifurcate to an alternative branch when they reach the somite stage. Here, dystrophin deficiency was linked to marked dysregulations of cell junction protein families involved in the cell state transitions characteristic of embryonic somitogenesis. Altogether, this work demonstrates that in vitro, dystrophin deficiency has deleterious effects on cell-cell communication during myogenic development, which should be considered in future therapeutic strategies for DMD.
