A5079515898- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Mesenchymal stem cell research
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Genetics, Aging, and Longevity in Model Organisms
- Ion channel regulation and function
- Exercise and Physiological Responses
- Muscle metabolism and nutrition
- Nutrition and Health in Aging
- CAR-T cell therapy research
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Xenotransplantation and immune response
- Inflammatory Myopathies and Dermatomyositis
Institut de Myologie
2016-2025
Centre National de la Recherche Scientifique
2013-2025
Centre de Recherche en Myologie
2016-2025
Sorbonne Université
2016-2025
Inserm
2016-2025
Pitié-Salpêtrière Hospital
2001-2024
Assistance Publique – Hôpitaux de Paris
2018-2024
Astrophysique, Instrumentation et Modélisation
2013-2022
Université Paris Cité
1998-2021
Université Sorbonne Paris Nord
2015
ABSTRACT Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion satellite cells, to form new fibres. This study was designed determine pattern expression in vivo two myogenic regulatory factors, Myf5 MyoD during this process. Cardiotoxin used induce regeneration gastrocnemius soleus muscles heterozygous Myf5-nlacZ mice, were assayed for presence β-galactosidase (Myf5) MyoD. Adult cells identified by M-cadherin labelling, when...
Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There currently no therapy for this disease. Here we report subpopulation of circulating cells expressing AC133, well-characterized marker hematopoietic stem cells, also expresses early myogenic markers. Freshly isolated, AC133+ were induced undergo myogenesis when cocultured with or exposed Wnt-producing in vitro delivered vivo through the...
Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by limited proliferative capacity of human myoblasts. Isolation reliable stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with aging, developing innovative gene-based, cell-based or pharmacological biotherapies.Using transduction telomerase-expressing cyclin-dependent kinase 4-expressing...
Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy vasculopathy. patients display upregulation of type I interferon-inducible genes in fibres, endothelial cells, peripheral blood. However, the effect interferon on tissue has not yet been determined. Our aim was to study pathogenicity vitro evaluate efficacy pathway blockade for therapeutic purposes. The activation...
In this study, we have investigated the consequences of aging on regenerative capacity human skeletal muscle by evaluating two parameters: (i) variation in telomere length which was used to evaluate vivo turn-over and (ii) proportion satellite cells calculated as compared total number nuclei a fibre. Two muscles different types innervation were analysed: biceps brachii, limb muscle, masseter, masticatory muscle. The biopsies obtained from groups: young adults (23 +/- 1.15 years old) aged (74...
In this study, we have evaluated the ability of human satellite cells isolated from subjects aged 5 days to 86 years proliferate in culture. Cells were cultivated until they became senescent. The number cell divisions was calculated by counting plated culture compared removed following proliferation. Telomere length, which is known decrease during each round division, has been used analyze vitro replicative capacity and vivo history at isolation. rate telomere shortening myonuclei these...
Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK was associated with unprecedented magnitude outbreak disease Indian Ocean. Clinically, this characterized invalidating poly-arthralgia, myalgia being reported 97.7% cases. cellular targets are unknown, we studied pathogenic events skeletal muscle.Immunohistology on muscle biopsies from two...
Summary Cultured human myoblasts fail to immortalize following the introduction of telomerase. The availability an immortalization protocol for normal would allow one isolate cellular models from various neuromuscular diseases, thus opening possibility develop and test novel therapeutic strategies. parameters limiting efficacy myoblast transfer therapy (MTT) could be assessed in such models. Finally, presence unlimited number cell divisions, ability clone cells after experimental...
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of functional dystrophin in muscles results fragility fiber membrane with progressive weakness and premature death. There no cure for DMD current treatment options focus primarily respiratory assistance, comfort care, delaying loss ambulation. Recent works support idea that stem cells can contribute repair as well replenishment satellite cell pool. Here we...
PDZ motifs are modular protein–protein interaction domains, consisting of 80–120 amino acid residues, whose function appears to be the direction intracellular proteins multiprotein complexes. In skeletal muscle, there a few known PDZ-domain proteins, which include neuronal nitric oxide synthase and syntrophin, both components dystrophin complex, actinin-associated LIM protein, binds spectrin-like repeats α-actinin-2. Here, we report identification characterization new muscle protein...
Genome editing with engineered nucleases has recently emerged as an approach to correct genetic mutations by enhancing homologous recombination a DNA repair template. However, many diseases, such Duchenne muscular dystrophy (DMD), can be treated simply correcting disrupted reading frame. We show that genome transcription activator-like effector (TALENs), without template, efficiently the frame and restore expression of functional dystrophin protein is mutated in DMD. TALENs were mediate...
Abstract Background Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence nonsense is often absence mutant gene expression due to activation an mRNA surveillance mechanism called nonsense-mediated decay (NMD). Strategies rescue nonsense-containing mRNAs have been developed such as NMD inhibition or mutation readthrough. Methods Using a dedicated screening system, we sought molecules capable block NMD. Additionally, 3 cell lines derived from...
Immune-mediated necrotizing myopathies (IMNM) may be associated with either anti-signal recognition protein (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies (Abs), and the titer of these Abs is correlated disease activity. We investigated whether anti-SRP anti-HMGCR could involved in muscle damage.Muscle biopsies patients were analyzed for atrophy regeneration by measuring fiber size performing immunostaining neonatal myosin heavy chain. To further understand role...
In recent years, numerous reports have identified in mouse different sources of myogenic cells distinct from satellite that exhibited a variable potential vivo. Myogenic stem also been described humans, although their regenerative has rarely quantified. this study, we investigated the human muscle-derived based on expression cell marker CD133 as compared to bona fide already used clinical trials. The efficiency these participate muscle regeneration and contribute renewal pool, when injected...
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant genetic disease mainly characterized by ptosis and dysphagia. We conducted phase I/IIa clinical study (ClinicalTrials.gov NCT00773227) using autologous myoblast transplantation following myotomy in adult OPMD patients. This included 12 patients with diagnosis of OPMD, indication for cricopharyngeal myotomy, confirmed diagnosis. The feasibility safety end points both the surgical procedure were assessed...
Macrophages have been shown to be essential for muscle repair by delivering trophic cues growing skeletal precursors and young fibers. Here, we investigated whether human macrophages, either proinflammatory or anti-inflammatory, coinjected with myoblasts into regenerating of Rag2(-/-) γC(-/-) immunodeficient mice, could modify in vivo the kinetics proliferation differentiation transplanted myogenic precursors. Our results clearly show that macrophages improve participation injected host...
Mutations in lamin A/C and emerin change myogenic cell fate by disrupting heterochromatin tethering to the nuclear envelope.
Myotonic dystrophy type 1 (DM1) is caused by (CTG⋅CAG)n-repeat expansion within the DMPK gene and thought to be mediated a toxic RNA gain of function. Current attempts develop therapy for this disease mainly aim at destroying or blocking abnormal properties mutant (CUG)n RNA. Here, we explored DNA-directed strategy demonstrate that single clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-cleavage in either its 5′ 3′ unique flank promotes uncontrollable deletion large...
Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response injury and modify its contractile metabolic properties changing demands. The major role growth, remodeling regeneration played by satellite cells, a quiescent population myogenic precursor cells that reside between basal lamina plasmalemma are rapidly activated appropriate stimuli. However, pathologic conditions or during aging, complete regenerative program can be...
Highlights•The capacity of human muscle stem cells to enter quiescence diminishes with age•This reduced re-quiesce is associated increased DNA methylation•DNA methylation suppresses SPRY1, a known regulator quiescence•Senescence, feature late cell division counts, not ageSummaryThe molecular mechanisms by which aging affects number and function are poorly understood. Murine data have implicated cellular senescence in the loss aging. Here, using carrying out experiments within strictly...
MyoD–Myomixer/Myomaker axis controls human myoblast fusion.