Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice

摘要: HDAC inhibitors (HDACi) exert beneficial effects in mdx mice, by promoting endogenous regeneration; however, the cellular determinants of HDACi activity on dystrophic muscles have not been determined. We show that fibroadipogenic progenitors (FAP) influence regeneration potential satellite cells during disease progression mice and mediate ability to selectively promote at early stages disease. FAPs from young promote, while old repress, cell-mediated formation myotubes. In inhibited FAP adipogenic potential, enhancing their differentiation adjacent cells, through upregulation soluble factor follistatin. By contrast, were resistant HDACi-mediated inhibition adipogenesis constitutively repressed transplantation regenerating restored increase myofibre size mice. These results reveal are key a previously unappreciated stage-specific effect muscles.