Phospho-tyrosine phosphastase inhibitor Bis-peroxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters

Understanding the regulation of the stem cell fate is fundamental for designing novel regenerative medicine strategies. Previous studies have suggested that pharmacological treatments with small molecules provide a robust and reversible regulation of the stem cell program. Previously, we showed that treatment with a vanadium compound influences muscle cell fate in vitro. In this study, we demonstrate that treatment with the phospho-tyrosine phosphatase inhibitor BpV (Bis-peroxovanadium) drives primary muscle cells to a poised stem cell stage, with enhanced function in muscle regeneration in vivo following transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self-renewal potential in vivo, and replenished the niche in both satellite and interstitial cell compartments. Moreover, we found that BpV treatment induces specific activating chromatin modifications at the promoter regions of genes associated with stem cell fate, including Sca-1 and Pw1. Thus, our findings indicate that BpV resets the cell fate program by specific epigenetic regulations, such that the committed myogenic cell fate is redirected to an earlier progenitor cell fate stage, which leads to an enhanced regenerative stem cell potential