Article Dans Une Revue iScience Année : 2024

Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells

Virginie Mournetas
David L Mack

Résumé

Mutations in the DMD gene lead to Duchenne muscular dystrophy (DMD), a severe neuromuscular disor-der affecting young boys as they acquire motor functions. DMD is typically diagnosed at 2–4 years of age, but the absence of dystrophin has negative impacts on skeletal muscles before overt symptoms appear in patients, which poses a serious challenge in current standards of care. Here, we investigated the conse-quences 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. Dystrophin deficiency was linked to marked dysregulations of cell junction proteins 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.
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hal-04901309 , version 1 (20-01-2025)

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Elise Mozin, Emmanuelle Massouridès, Virginie Mournetas, Clémence Lièvre, Audrey Bourdon, et al.. Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells. iScience, 2024, 27 (7), pp.110242. ⟨10.1016/j.isci.2024.110242⟩. ⟨hal-04901309⟩
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