Muscle fiber Myc is dispensable for muscle growth and its forced expression severely perturbs homeostasis

Daniel J. Ham (), Michelangelo Semeraro, Bianca M. Berger, Timothy J. McGowan, Shuo Lin, Eleonora Maino, Filippo Oliveri and Markus A. Rüegg ()
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Daniel J. Ham: University of Basel
Michelangelo Semeraro: University of Basel
Bianca M. Berger: University of Basel
Timothy J. McGowan: University of Basel
Shuo Lin: University of Basel
Eleonora Maino: University of Basel
Filippo Oliveri: University of Basel
Markus A. Rüegg: University of Basel

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract The oncogenic transcription factor Myc stimulates many growth processes including cell cycle progression and ribosome biogenesis. Myc expression is low in adult skeletal muscle, but is upregulated upon growth stimuli. Furthermore, muscle fiber Myc overexpression recapitulates many aspects of growth-related gene expression, leading to the hypothesis that Myc mediates pro-growth responses to anabolic stimuli, such as exercise. Here, we test this hypothesis by examining mouse models in which Myc is specifically eliminated or overexpressed in skeletal muscle fibers or muscle stem cells (MuSC). While muscle fiber Myc expression increased during muscle growth and Myc expression in MuSCs was required for successful muscle regeneration, muscle fiber Myc expression was dispensable for post-natal, mechanical overload or PKBα/Akt1-induced muscle growth in mice. Similarly, constitutive Myc expression did not promote skeletal muscle hypertrophy, but instead impaired muscle fiber structure and function within days. These data question the role of Myc in skeletal muscle growth.

Date: 2025
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DOI: 10.1038/s41467-025-58542-7

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