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Suppressing PDGFRβ Signaling Enhances Myocyte Fusion to Promote Skeletal Muscle Regeneration

Xue, S.; Benvie, A. M.; Blum, J. E.; Kolba, N. J.; Cosgrove, B. D.; Thalacker-Mercer, A.; Berry, D. C.

2024-10-18 developmental biology
10.1101/2024.10.15.618247 bioRxiv
Show abstract

Muscle cell fusion is critical for forming and maintaining multinucleated myotubes during skeletal muscle development and regeneration. However, the molecular mechanisms directing cell-cell fusion are not fully understood. Here, we identify platelet-derived growth factor receptor beta (PDGFR{beta}) signaling as a key modulator of myocyte fusion in adult muscle cells. Our findings demonstrate that genetic deletion of Pdgfr{beta} enhances muscle regeneration and increases myofiber size, whereas PDGFR{beta} activation impairs muscle repair. Inhibition of PDGFR{beta} activity promotes myonuclear accretion in both mouse and human myotubes, whereas PDGFR{beta} activation stalls myotube development by preventing cell spreading to limit fusion potential. Transcriptomics analysis show that PDGFR{beta} signaling cooperates with TGF{beta} signaling to direct myocyte size and fusion. Mechanistically, PDGFR{beta} signaling requires STAT1 activation, and blocking STAT1 phosphorylation enhances myofiber repair and size during regeneration. Collectively, PDGFR{beta} signaling acts as a regenerative checkpoint and represents a potential clinical target to rapidly boost skeletal muscle repair.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.