Publications by authors named "Jacob Kocan"

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

Cell Rep 2021 May;35(6):109098

Department of Orthopaedic Surgery, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Regenerative Medicine, Musculoskeletal Regeneration Program, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.celrep.2021.109098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183356PMC
May 2021