Persistent NF-κB activation in muscle stem cells induces proliferation-independent telomere shortening

Elisia D. Tichy, Nuoying Ma, David Sidibe, Emanuele Loro, Jacob Kocan, Delia Z. Chen, Tejvir S. Khurana, Paul Hasty, Foteini Mourkioti

Research output: Contribution to journalArticlepeer-review

Abstract

During the repeated cycles of damage and repair in many muscle disorders, including Duchenne muscular dystrophy (DMD), the muscle stem cell (MuSC) pool becomes less efficient at responding to and repairing damage. The underlying mechanism of such stem cell dysfunction is not fully known. Here, we demonstrate that the distinct early telomere shortening of diseased MuSCs in both mice and young DMD patients is associated with aberrant NF-κB activation. We find that prolonged NF-κB activation in MuSCs in chronic injuries leads to shortened telomeres and Ku80 dysregulation and results in severe skeletal muscle defects. Our studies provide evidence of a role for NF-κB in regulating stem-cell-specific telomere length, independently of cell replication, and could be a congruent mechanism that is applicable to additional tissues and/or diseases characterized by systemic chronic inflammation.

Original languageEnglish (US)
Article number109098
JournalCell Reports
Volume35
Issue number6
DOIs
StatePublished - May 11 2021

Keywords

  • MuSCs
  • NF-κΒ
  • chronic injury
  • muscle disease
  • muscle stem cells
  • muscular dystrophy
  • telomere biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Persistent NF-κB activation in muscle stem cells induces proliferation-independent telomere shortening'. Together they form a unique fingerprint.

Cite this