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Article Dans Une Revue Stem Cell Reports Année : 2022

Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy

Robin Duelen
  • Fonction : Auteur
Domiziana Costamagna
  • Fonction : Auteur
Liesbeth de Waele
  • Fonction : Auteur
Nathalie Goemans
  • Fonction : Auteur
Kaat Desloovere
  • Fonction : Auteur
Catherine Verfaillie
  • Fonction : Auteur
Karin Sipido
  • Fonction : Auteur
Gunnar Buyse
  • Fonction : Auteur
Maurilio Sampaolesi

Résumé

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant cardiomyopathies result from mutations in genes encoding proteins of the dystrophin-associated protein complex (DAPC), which is a multi-protein membrane-spanning complex. We examined the expression of DAPC components in hiPSC-CM, which underwent maturation in 2D and 3D culture protocols. The results were compared with human adult cardiac tissue and isolated cardiomyocytes. We found that similarly to adult cardiomyocytes, hiPSC-CM express dystrophin, in line with previous studies on Duchenne’s disease. β-dystroglycan was also expressed, but, contrary to findings in adult cardiomyocytes, none of the sarcoglycans nor α-dystroglycan were, despite the presence of their mRNA. In conclusion, despite the robust expression of dystrophin, the absence of several other DAPC protein components cautions for reliance on commonly used protocols for hiPSC-CM maturation for functional assessment of the complete DAPC.

Dates et versions

hal-04491703 , version 1 (06-03-2024)

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Citer

Robin Duelen, Domiziana Costamagna, Guillaume Gilbert, Liesbeth de Waele, Nathalie Goemans, et al.. Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy. Stem Cell Reports, 2022, 17 (2), pp.352-368. ⟨10.1016/j.stemcr.2021.12.019⟩. ⟨hal-04491703⟩
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