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Communication Dans Un Congrès Année : 2023

A robust and practical myogenic system to explore cellular and genomic features of muscle differentiation

Résumé

Lamins are the main constituents of the nuclear lamina, a protein meshwork underlining the inner face of the nuclear envelope (NE) and facing chromatin and nucleoplasm. A-type lamins (lamin A and C), encoded by the LMNA gene, have roles in the chromatin organization, through domains called Lamin-Associated Domains (LAD). Proper maintenance of chromatin organization is essential for normal cell function, and depends on nuclear envelope stability and tissue-specific nuclear envelope proteins. LMNA gene mutations are responsible for a wide spectrum of disorders called laminopathies, most of them affecting striated muscles. LMNA mutations have been associated with defects in LAD organization and gene expression at the nuclear periphery, contributing in the pathophysiological mechanisms of laminopathies. Laminopathies are characterized by a strong clinical variability and genetic or epigenetic factors, such as modifier genes or specific chromatin organization defects could explain such variability. We collected biological materials, through national and international collaborations and we received a majority of fibroblasts from LMNA-mutated patients. Genome organization being highly different between cell types, we myo-converted immortalized skin fibroblasts into myogenic cells, via overexpression of murine MyoD. We performed a study to validate this model as relevant to investigate LAD organization, by combining RNA-seq and ChIP-seq targeting Lamin A/C and histone marks. We showed that myotubes derived from these myo-converted fibroblasts underwent a clear phenotypic switch to myogenic cell type, at a transcriptomic and at a chromatin level, hence validating this cell system to study LAD organization in muscle cells.
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Dates et versions

hal-04280205 , version 1 (10-11-2023)

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L. Benarroch, J. Madsen-Østerbye, M. Abdelhalim, K. Mamchaoui, J. Ohana, et al.. A robust and practical myogenic system to explore cellular and genomic features of muscle differentiation. 28th International Annual Congress of the World Muscle Society, Oct 2023, Charleston, United States. pp.S158, ⟨10.1016/j.nmd.2023.07.363⟩. ⟨hal-04280205⟩
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