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Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells
by
Kefi, Kaouthar
, Bruno, Claudio
, Authier, François-Jerome
, Pharm, Juliette Nectoux
, Cardone, Nastasia
, Desguerre, Isabelle
, Panicucci, Chiara
, Taglietti, Valentina
, Fiorillo, Chiara
, Baratto, Serena
, Malfatti, Edoardo
, Lafuste, Peggy
, Pharm, France Leturcq
, Periou, Baptiste
, Barnerias, Christine
, Relaix, Frederic
, Gitiaux, Ciryl
in
Age
/ Analysis
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ Cellular senescence
/ Duchenne muscular dystrophy
/ Dystrophin
/ FAPs
/ Fibrosis
/ Genetic aspects
/ Health aspects
/ Life Sciences
/ Muscle regeneration
/ Muscular dystrophy
/ Mutation
/ Neurology
/ Neurosciences
/ Pathology
/ Proteins
/ Software
/ Statistical analysis
/ Stem cells
2023
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Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells
by
Kefi, Kaouthar
, Bruno, Claudio
, Authier, François-Jerome
, Pharm, Juliette Nectoux
, Cardone, Nastasia
, Desguerre, Isabelle
, Panicucci, Chiara
, Taglietti, Valentina
, Fiorillo, Chiara
, Baratto, Serena
, Malfatti, Edoardo
, Lafuste, Peggy
, Pharm, France Leturcq
, Periou, Baptiste
, Barnerias, Christine
, Relaix, Frederic
, Gitiaux, Ciryl
in
Age
/ Analysis
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ Cellular senescence
/ Duchenne muscular dystrophy
/ Dystrophin
/ FAPs
/ Fibrosis
/ Genetic aspects
/ Health aspects
/ Life Sciences
/ Muscle regeneration
/ Muscular dystrophy
/ Mutation
/ Neurology
/ Neurosciences
/ Pathology
/ Proteins
/ Software
/ Statistical analysis
/ Stem cells
2023
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Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells
by
Kefi, Kaouthar
, Bruno, Claudio
, Authier, François-Jerome
, Pharm, Juliette Nectoux
, Cardone, Nastasia
, Desguerre, Isabelle
, Panicucci, Chiara
, Taglietti, Valentina
, Fiorillo, Chiara
, Baratto, Serena
, Malfatti, Edoardo
, Lafuste, Peggy
, Pharm, France Leturcq
, Periou, Baptiste
, Barnerias, Christine
, Relaix, Frederic
, Gitiaux, Ciryl
in
Age
/ Analysis
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ Cellular senescence
/ Duchenne muscular dystrophy
/ Dystrophin
/ FAPs
/ Fibrosis
/ Genetic aspects
/ Health aspects
/ Life Sciences
/ Muscle regeneration
/ Muscular dystrophy
/ Mutation
/ Neurology
/ Neurosciences
/ Pathology
/ Proteins
/ Software
/ Statistical analysis
/ Stem cells
2023
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Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells
Journal Article
Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells
2023
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Overview
Duchenne muscular dystrophy (DMD) is a devastating X-linked muscular disease, caused by mutations in the
DMD
gene encoding Dystrophin and affecting 1:5000 boys worldwide. Lack of Dystrophin leads to progressive muscle wasting and degeneration resulting in cardiorespiratory failure. Despite the absence of a definitive cure, innovative therapeutic avenues are emerging. Myopathologic studies are important to further understand the biological mechanisms of the disease and to identify histopathologic benchmarks for clinical evaluations. We conducted a myopathologic analysis on twenty-four muscle biopsies from DMD patients, with particular emphasis on regeneration, fibro-adipogenic progenitors and muscle stem cells behavior. We describe an increase in content of fibro-adipogenic progenitors, central orchestrators of fibrotic progression and lipid deposition, concurrently with a decline in muscle regenerative capacity. This regenerative impairment strongly correlates with compromised activation and expansion of muscle stem cells. Furthermore, our study uncovers an early acquisition of a senescence phenotype by DMD-afflicted muscle stem cells. Here we describe the myopathologic trajectory intrinsic to DMD and establish muscle stem cell senescence as a pivotal readout for future therapeutic interventions.
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