Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1

Silvia Dibenedetto, Maria Niklison-Chirou, Claudia P. Cabrera, Matthew Ellis, Lesley G. Robson, Paul Knopp, Francesco Saverio Tedesco, Martina Ragazzi, Valentina Di Foggia, Michael R. Barnes, Aleksandar Radunovic, Silvia Marino

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model. These preclinical data in mouse models and human cells provide a strong rationale for the development of pharmacological approaches to target BMI1-mediated mitochondrial regulation and protection from DNA damage to sustain the regenerative potential of the skeletal muscle in conditions of chronic muscle wasting.

Original languageEnglish
Pages (from-to)528-542
Number of pages15
JournalStem Cell Reports
Volume9
Issue number2
DOIs
Publication statusPublished - 8 Aug 2017

Keywords

  • DMD
  • muscle regeneration
  • myoblasts
  • myopathy
  • oxidative phosphorylation
  • Polycomb gene
  • satellite cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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