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Publication : Three-dimensional imaging studies in mice identify cellular dynamics of skeletal muscle regeneration.

First Author  Collins BC Year  2024
Journal  Dev Cell Volume  59
Issue  11 Pages  1457-1474.e5
PubMed ID  38569550 Mgi Jnum  J:377990
Mgi Id  MGI:8279165 Doi  10.1016/j.devcel.2024.03.017
Citation  Collins BC, et al. (2024) Three-dimensional imaging studies in mice identify cellular dynamics of skeletal muscle regeneration. Dev Cell 59(11):1457-1474.e5
abstractText  The function of many organs, including skeletal muscle, depends on their three-dimensional structure. Muscle regeneration therefore requires not only reestablishment of myofibers but also restoration of tissue architecture. Resident muscle stem cells (SCs) are essential for regeneration, but how SCs regenerate muscle architecture is largely unknown. We address this problem using genetic labeling of mouse SCs and whole-mount imaging to reconstruct, in three dimensions, muscle regeneration. Unexpectedly, we found that myofibers form via two distinct phases of fusion and the residual basement membrane of necrotic myofibers is critical for promoting fusion and orienting regenerated myofibers. Furthermore, the centralized myonuclei characteristic of regenerated myofibers are associated with myofibrillogenesis and endure months post injury. Finally, we elucidate two cellular mechanisms for the formation of branched myofibers, a pathology characteristic of diseased muscle. We provide a synthesis of the cellular events of regeneration and show that these differ from those used during development.
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