title: Correction of the FSHD myoblast differentiation defect by fusion with healthy myoblasts.
abstract: Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease with a prevalence that could reach 1 in 8,000 characterized by progressive asymmetric muscle weakness. Myoblasts isolated from FSHD muscles exhibit morphological differentiation defects and show a distinct transcription profile. These abnormalities may be linked to the muscle weakness in FSHD patients. We have tested whether fusion of FSHD myoblasts with primary myoblasts isolated from healthy individuals could correct the differentiation defects. Our results show that the number of hybrid myotubes with normal phenotype increased with the percentage of normal myoblasts initially cultured. We demonstrated that a minimum of 50% of normal nuclei is required for a phenotypic correction of the FSHD phenotype. Moreover, transcriptomic profiles of phenotypically corrected hybrid myotubes showed that the expression of deregulated genes in FSHD myotubes became almost normal. The number of deregulated pathways also decreased from 39 in FSHD myotubes to one in hybrid myotubes formed with 40% FSHD and 60% normal myoblasts. We thus propose that while phenotypical and functional correction of FSHD is feasible, it requires more than 50% of normal myoblasts, it creates limitations for cell therapy in the FSHD context.
authors.affiliation: UMR 8126, University of Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Dib
authors.affiliation: UMR 8126, University of Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Yara
authors.initials: Y
authors.lastname: Bou Saada
authors.affiliation: UMR 8126, University of Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Petr
authors.initials: P
authors.lastname: Dmitriev
authors.affiliation: Functional Genomics Unit, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Richon
authors.affiliation: Functional Genomics Unit, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.affiliation: INSERM U-1046, 371 Avenue du Doyen Gaston Giraud, F-34295 Montpellier, France.
authors.forename: Dalila
authors.initials: D
authors.lastname: Laoudj-Chenivesse
authors.affiliation: INSERM U-1046, 371 Avenue du Doyen Gaston Giraud, F-34295 Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Carnac
authors.affiliation: UMR 8126, University of Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipinski
authors.affiliation: UMR 8126, University of Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Yegor S
authors.initials: YS
authors.lastname: Vassetzky
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology*; D010641:Phenotype; D055815:Young Adult