| First Author | Tichy ED | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 6 | Pages | 109098 |
| PubMed ID | 33979621 | Mgi Jnum | J:317321 |
| Mgi Id | MGI:6717016 | Doi | 10.1016/j.celrep.2021.109098 |
| Citation | Tichy ED, et al. (2021) Persistent NF-kappaB activation in muscle stem cells induces proliferation-independent telomere shortening. Cell Rep 35(6):109098 |
| abstractText | 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-kappaB activation. We find that prolonged NF-kappaB 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-kappaB 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. |
