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Mass-spectrometry results from fibroadipogenic progenitor cells isolated from healthy controls (n=3) and DMD patients (n=3)

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posted on 2025-03-25, 10:54 authored by Esther Fernandez SimonEsther Fernandez Simon

Duchenne muscular dystrophy is a genetic disease produced by mutations in the dystrophin gene characterized by early onset muscle weakness leading to severe and irreversible disability. Muscle degeneration involves a complex interplay between multiple cell lineages spatially located within areas of damage, termed the 33 degenerative niche, including inflammatory cells, satellite cells (SCs) and fibro-adipogenic precursor cells (FAPs). FAPs are mesenchymal stem cell which have a pivotal role in muscle homeostasis as they can either promote muscle regeneration or contribute to muscle degeneration by expanding fibrotic and fatty tissue. Although it has been described that FAPs could have a different behaviour in DMD patients than in healthy controls, the molecular pathways regulating their function as well as their gene expression profile are unknown. We used quantitative proteomics using a Lumos Orbitrap mass spectrometer to elucidate the differences in the proteomic profile of isolated FAPs from healthy and DMD patients. Samples were analysed with the MaxQuant software (version1.6.1.0) through the human Swissprot database. To reveal the precise biological properties of each condition, we used Metascape. Proteins with a log2FC > 0.5 were analysed for each condition. Top proteins upregulated in the healthy condition were involved in cell homeostasis such as protein localization between organelles in the cell, membrane organization or regulation of muscle adaptation. However, upregulated proteins in the DMD condition were involved with mRNA metabolic process, regulation of angiogenesis or adherent’s junctions.

Funding

Academy of Medical Sciences Professorship Scheme (APR4/1007)

Medical Research Council (MR/W019086/1)

AFM (AFM-24341 research grant)

Fundación Isabel Gemio 413

La Marató de TV3 (#202034-10)

NIHR Newcastle Biomedical Research Centre

National Institute for Health Research

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