Résumé :
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Background : Exosomes are vesicles derived from the late endosomal system secreted constitutively. As we have found that muscle cells secrete exosomes, we addressed the question whether skeletal muscle exosomes contained specific miRNAs and whether they could act as endocrine signals during myogenesis. Results: We compared the miRNA repertoires sorted in exosomes from C2C12 myoblasts and myotubes. The majority of muscle cell miRNAs were exported in exosomes (171 and 182 miRNAs, in exosomes from myoblasts and myotubes, respectively). However, some miRNAs were found expressed at higher levels in exosomes than in their donor cells and vice versa. Interestingly, miRNAs from C2C12 exosomes were regulated during myogenesis. Functional analysis of their predicted target genes indicated that these regulated miRNAs were involved in the control signaling pathways. We found that two miRNAs (i.e. ; miR-133a and miR-145) which are normally not expressed in proliferating myoblasts, were detected in myoblasts incubated with myotube exosomes but not with myoblast exosomes. Exosome from myotubes could also transfer other small RNAs (siRNA) in myoblasts. By using Sirtuin 1 as reported gene, we demonstrated that miRNAs secreted by myotubes are functional and can silence Sirtuin 1 at the protein level in myoblasts. As Sirtuin 1 regulates muscle gene expression and differentiation, our results show that miRNAs from exosome myotubes could contribut in the commitment of myoblasts in the process of differentiation. Conclusion: Exosomal transfer of siRNA would be a new powerful mean of orchestrating gene expression to coodinate myoblast cell differentiation during the induction of cell-cycle quiescence.
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