Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters

FASEB J. 2016 Apr;30(4):1404-15. doi: 10.1096/fj.15-275420. Epub 2015 Dec 15.


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 fatein vitro In this study, we demonstrate that treatment with the phosphotyrosine phosphatase inhibitor bisperoxovanadium (BpV) drives primary muscle cells to a poised stem cell stage, with enhanced function in muscle regenerationin vivofollowing transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self-renewal potentialin vivoand 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, includingSca-1andPw1 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.-Smeriglio, P., Alonso-Martin, S., Masciarelli, S., Madaro, L., Iosue, I., Marrocco, V., Relaix, F., Fazi, F., Marazzi, G., Sassoon, D. A., Bouché, M. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functionsviaepigenetic modulation of Sca-1 and Pw1 promoters.

Keywords: PW1 interstitial cells; cell reprogramming; cell stemness; muscle cell fate; muscle regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / genetics*
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Epigenesis, Genetic*
  • Gene Expression / drug effects
  • Kruppel-Like Transcription Factors / genetics*
  • Membrane Proteins / genetics*
  • Mice, Nude
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Muscle Cells / cytology
  • Muscle Cells / drug effects*
  • Muscle Cells / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / injuries
  • Muscle, Skeletal / physiopathology
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / drug effects*
  • Myoblasts, Skeletal / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / metabolism
  • Regeneration / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vanadium Compounds / pharmacology*


  • Antigens, Ly
  • Kruppel-Like Transcription Factors
  • Ly6a protein, mouse
  • Membrane Proteins
  • Peg3 protein, mouse
  • Vanadium Compounds
  • bisperoxovanadium
  • Protein Tyrosine Phosphatases