Researchers from the I-Stem and Genethon laboratories have explored the relevance of human induced pluripotent stem cells (hiPSC) for the cellular modeling of limb-girdle muscular dystrophy (LGMD).
- The model proves to be applicable to a large number of LGMDs: the analysis of skeletal muscle cells, differentiated from hiPSCs derived from fibroblasts of non-diseased patients, shows an expression of the majority of genes and proteins at the origin of LGMDs.
- The interest of the model is confirmed for LGMD R9: hiPSC-derived muscle cells from fibroblasts of patients with FKRP-related LGMD R9 reproduce the characteristics of the disease.
- The model recapitulates the phenotypic variability of the disease: as observed in patients, skeletal myotubes generated from hiPSCs carrying different mutations show an absence of the FKRP protein which does not systematically lead to a decrease in alpha-dystroglycan glycosylation.