A5052890795- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Neurogenetic and Muscular Disorders Research
- Mesenchymal stem cell research
- RNA Research and Splicing
- RNA modifications and cancer
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Cardiomyopathy and Myosin Studies
- Adipose Tissue and Metabolism
- Inflammatory Myopathies and Dermatomyositis
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Sarcoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
Université Paris-Est Créteil
2015-2024
École Nationale Vétérinaire d'Alfort
2015-2024
Institut Mondor de Recherche Biomédicale
2015-2024
Assistance Publique – Hôpitaux de Paris
2007-2024
Inserm
2015-2024
Hôpitaux Universitaires Henri-Mondor
2017-2023
Établissement Français du Sang
2015-2021
Institut National de Recherche en Santé Publique
2021
Biomedical Research Institute
2020
Institut de Myologie
2009-2018
Muscle satellite cells contribute to muscle regeneration. We have used a Pax3 GFP/+ mouse line directly isolate (Pax3)(green fluorescent protein)–expressing cells, by flow cytometry from adult skeletal muscles, as homogeneous population of small, nongranular, Pax7+, CD34+, CD45–, Sca1– cells. The parameters thus established enabled us wild-type muscles. Such grafted into muscles mdx nu/nu mice, contributed both fiber repair and the cell compartment. Expansion these in culture before...
The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression Pax7. We show Pax3, paralogue Pax7, is also present in both quiescent activated many muscles. Dominant-negative forms Pax3 -7 repress MyoD, but do not interfere with other myogenic determination factor, Myf5, which, together Pax3/7, regulates differentiation these cells. In Pax7 mutants, progressively lost Pax3-expressing -nonexpressing this caused cell death, effects...
Skeletal muscle growth and regeneration are attributed to satellite cells - stem resident beneath the basal lamina that surrounds each myofibre. Quiescent express transcription factor Pax7 when activated, coexpress with MyoD. Most then proliferate, downregulate differentiate. By contrast, others maintain but lose MyoD return a state resembling quiescence. Here we show is able drive in quiescent activated cells, continues do so those subsequently cease proliferation withdraw from immediate...
State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming capture their in vivo state. However, majority cell isolation protocols involve lengthy mechanical enzymatic dissociation steps followed by flow cytometry, exposing stress disrupting physiological niche. Focusing on adult skeletal muscle stem cells, we a protocol that circumvents impact procedures captures native quiescent We show current induce major transcriptional changes accompanied...
Abstract Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression coordinately regulated in their numerous nuclei. Here we show by snRNA-seq and snATAC-seq that slow, fast, myotendinous neuromuscular junction myonuclei each have different transcriptional programs, associated with distinct chromatin states combinations of transcription factors. In adult mice, identified myofiber types predominantly express either a slow or one the three fast isoforms...
Pax genes encode evolutionarily conserved transcription factors that play critical roles in development. Pax3 and Pax7 constitute one of the four subfamilies. Despite partially overlapping expression domains, mouse mutations for have very different consequences. To investigate mechanism these contrasting phenotypes, we replaced by using gene targeting mouse. can substitute function dorsal neural tube, crest cell, somite development, but not formation muscles involving long-range migration...
We address the molecular control of myogenesis in progenitor cells derived from hypaxial somite. Null mutations Pax3 , a key regulator skeletal muscle formation, lead to cell death this domain. have developed novel allele encoding Pax3–engrailed fusion protein that acts as transcriptional repressor. Heterozygote mouse embryos an attenuated mutant phenotype, with partial conservation somite and its myogenic derivatives, including some hindlimb muscles. At these sites, expression Myf5 is...
Myostatin, a member of the TGF-beta family, has been identified as powerful inhibitor muscle growth. Absence or blockade myostatin induces massive skeletal hypertrophy that is widely attributed to proliferation population fiber-associated satellite cells have principle source new tissue during growth and regeneration. Postnatal proposed basis for therapeutic strategies combat loss in genetic acquired myopathies. But this approach, according accepted mechanism, would raise threat premature...
Maternal diabetes increases risk for congenital malformations, particularly cardiac outflow tract defects. inhibits expression of Pax3 in neuroepithelium through hyperglycemia-induced oxidative stress. The gives rise to the neural crest, and crest (CNC) is required CNC migration heart septation. Here we tested whether maternal diabetes, stress, before onset delamination, impairs septation.CNC was mapped mouse embryos whose mothers were diabetic, or transiently hyperglycemic, which stress...
Fibro-adipogenic progenitors (FAPs) are an interstitial cell population in adult skeletal muscle that support regeneration. During development, connective tissue (MCT) cells proper patterning, however the underlying molecular mechanisms not well understood and it remains unclear whether FAPs embryonic MCT share a common lineage. We show here mouse limb expressing transcription factor Osr1, differentiate into fibrogenic adipogenic vivo vitro defining FAP-like population. Genetic lineage...
The satellite cells, which serve as adult muscle stem are both located beneath myofiber basement membranes and closely associated with capillary endothelial cells. We observed that 90% of capillaries were pericytes in mouse human muscle. During post-natal growth, newly formed vessels their neuroglial 2 proteoglycan (NG2)-positive became progressively the myofibers increased size cells entered into quiescence. In vitro, muscle-derived promoted myogenic cell differentiation through...
Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypomethylation of D4Z4 repeats on chromosome 4q causing expression the DUX4 transcription factor. However, difficult detect in FSHD muscle biopsies and it debatable how robust changes target gene are as an biomarker. PAX7 master regulator myogenesis that rescues DUX4-mediated apoptosis. Here, we show suppression genes hallmark FSHD, major signature expression. This shown using meta-analysis over six...
Abstract Duchenne muscular dystrophy (DMD) is a severe degenerative disorder caused by mutations in the dystrophin gene. Dystrophin-deficient muscles are characterised progressive myofibre necrosis which inflammation plays deleterious role. However, molecular mechanisms underlying inflammation-induced muscle cells unknown. Here we show that necroptosis mechanism death dystrophin-deficient muscle. RIPK1, RIPK3 and MLKL upregulated dystrophic mouse myofibres. In human DMD samples, there strong...