A5030255436- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Virus-based gene therapy research
- Telomeres, Telomerase, and Senescence
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Nuclear Structure and Function
- Mesenchymal stem cell research
- Amyotrophic Lateral Sclerosis Research
- Genetics, Aging, and Longevity in Model Organisms
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neural Engineering
- RNA modifications and cancer
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Exercise and Physiological Responses
Institut de Myologie
2015-2025
Centre de Recherche en Myologie
2016-2025
Sorbonne Université
2016-2025
Inserm
2016-2025
Centre National de la Recherche Scientifique
2011-2024
Pitié-Salpêtrière Hospital
2012-2024
Assistance Publique – Hôpitaux de Paris
2024
Astrophysique, Instrumentation et Modélisation
2013-2023
Université Paris Cité
2015-2021
Centre de Recherche Saint-Antoine
2021
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...
Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing fibers. This limits their application study adult neuromuscular junction (NMJ) development, a process requiring maturation fibers in presence motor neuron endplates. Here we describe three-dimensional (3D) co-culture method whereby progenitors mixed with pluripotent stem cell-derived neurons self-organize form functional NMJ connections. Functional connectivity between...
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...
The mechanisms underlying cell response to mechanical forces are critical for muscle development and functionality. We aim determine whether mutations of the LMNA gene causing congenital muscular dystrophy impair ability precursors sense tissue stiffness respond challenge. found that LMNA-mutated myoblasts (LMNA) embedded in soft matrix did not align along gel axis whereas control did. were unable tune their cytoskeletal tension as attested by inappropriate cell-matrix adhesion sites versus...
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...
Research Article10 October 2016Open Access Source DataTransparent process A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss Emilia Servián-Morilla Neuromuscular Disorders Unit, Department of Neurology, Instituto de Biomedicina Sevilla, Hospital U. Virgen del Rocío/CSIC/Universidad Spain Centro Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Search for more papers by this author Hideyuki Takeuchi...
MyoD–Myomixer/Myomaker axis controls human myoblast fusion.
Abstract Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical understand the mechanisms through which venom toxins induce envenomation effects including local damage. Here, we demonstrate how venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using cultured myoblast cell line. The data suggest that both viability myoblasts. Russell’s reduced...
Aging of human skeletal muscle results in a decline mass and force, excessive turnover fibres, such as muscular dystrophies, further increases this decline. Although it has been shown rodents, by cross-age transplantation whole muscles, that the environment plays an important role process, implication proliferating aging progenitors poorly investigated, particularly humans, since regulation cell proliferation differs between rodents humans. The myogenic differentiation myoblasts is regulated...
Dysferlin deficiency compromises the repair of injured muscle, but underlying cellular mechanism remains elusive. To study this phenomenon, we have developed mouse and human myoblast models for dysferlinopathy. These dysferlinopathic myoblasts undergo normal differentiation a deficit in their ability to focal injury cell membrane. Imaging cells undergoing showed that dysferlin-deficit decreased number lysosomes present at membrane, resulting delay reduction injury-triggered lysosomal...
hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically pertinent models of various neuromuscular disorders and in numerous fundamental studies function. However, the cycle is linked to other cellular processes such integrin regulation, PI3K/Akt pathway, microtubule stability, raising question whether genetic modification related results secondary effects that could undermine validity these models. Here we...
Abstract Caveolin-3 is the major structural protein of caveolae in muscle. Mutations CAV3 gene cause different types myopathies with altered membrane integrity and repair, expression muscle proteins, regulation signaling pathways. We show here that myotubes from patients bearing P28L R26Q mutations present a dramatic decrease at plasma membrane, resulting abnormal response to mechanical stress. Mutant are unable buffer increase tension induced by This results impaired IL6/STAT3 pathway...
Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of plasma invagination, T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in mutations several their constituents induce muscle weakness myopathies. Here, we demonstrate that, at membrane, Bin1 caveolin-3 assemble into...
Amyotrophic lateral sclerosis (ALS) is characterized by progressive denervation leading to muscle atrophy prevented, during the early phase, compensatory reinnervation. Little known about fibre regeneration capacity in ALS. We have carried out vivo and vitro investigation of skeletal Seven ALS patients underwent a deltoid biopsy. Immunohistochemical analysis revealed various degrees denervation- reinnervation-related changes biopsies including satellite cells (SCs) activation regenerating...
A lysosome activator ameliorates muscular dystrophies.
Glucose transporter 4 (GLUT4) is sequestered inside muscle and fat then released by vesicle traffic to the cell surface in response postprandial insulin for blood glucose clearance. Here, we map biogenesis of this GLUT4 pathway humans, which involves clathrin isoform CHC22. We observe that transits through early secretory more slowly than constitutively secreted GLUT1 localize CHC22 ER-to-Golgi intermediate compartment (ERGIC). functions transport from ERGIC, as demonstrated an essential...
Abstract Cell‐based approaches to tissue repair suffer from rapid cell death upon implantation, limiting the window for therapeutic intervention. Despite robust lineage‐specific differentiation potential in vitro, function of transplanted mesenchymal stromal cells (MSCs) vivo is largely attributed their potent secretome comprising a variety growth factors (GFs). Furthermore, GF secretion markedly increased when MSCs are formed into spheroids. Native GFs sequestered within extracellular...