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

Piera Smeriglio, Sonia Alonso-Martin, Silvia Masciarelli, Luca Madaro, Ilaria Iosue, Valeria Marrocco, Frédéric Relaix, Francesco Fazi, Giovanna Marazzi, David A. Sassoon, Marina Bouché

Research output: Contribution to journalArticlepeer-review

Abstract

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 andreversible regulation of the stemcellprogram. Previously, we showed that treatment with a vanadium compound influences muscle cell fate in vitro. Inthis 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 regeneration in vivo following transplantation into injured muscles. Importantly, BpVtreated 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 associatedwith 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.

Original languageEnglish
Pages (from-to)1404-1415
Number of pages12
JournalFASEB Journal
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • Cell reprogramming
  • Cell stemness
  • Muscle cell fate
  • Muscle regeneration
  • PW1 interstitial cells

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters'. Together they form a unique fingerprint.

Cite this