Résumé :
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Efficient muscle regeneration requires cross talk between multiple cell types via secreted signalling molecules. However, as yet there has been no comprehensive analysis of this secreted signalling network in order to understand how it regulates myogenesis in humans. Using an integrated proteomic strategy, we identified 965 proteins secreted by differentiated muscle cells, comprising the human muscle cell secretome. While some were conventionally secreted soluble signalling proteins that act via cell surface receptors, the majority were intracellular proteins packaged in microvesicles, which also contained muscle cell RNA. These microvesicles could be subdivided into exosomal-like nanovesicles and morphologically distinct microvesicles, which differed in content, as well as docking and fusion kinetics with adjacent cells, suggesting distinct functions in myogenesis. Muscle-derived microvesicles can deliver functional protein directly into target cells, demonstrating they can effectively mediate intercellular communication. Thus, the intercellular signalling networks invoked during muscle differentiation and regeneration employ conventional soluble signalling molecules acting in concert with muscle-derived microvesicles delivering protein and potentially RNA cargos directly into target cells.
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