Early regulation and alternative splicing dynamics in glucocorticoid muscle atrophy revealed by temporal omics in C2C12 myotubes.

Skeletal muscle atrophy and weakness are major contributors to morbidity, prolonged recovery, and long-term disability across a wide range of diseases. Atrophy is caused by the breakdown of sarcomeric proteins, resulting in loss of muscle mass and strength. Molecular mechanisms underlying the onset of muscle atrophy and its progression have been analyzed in patients, mice, and cell culture, but the complementarity of these model systems remains to be explored. Here, we applied deep coverage transcriptomic and proteomic profiling for an updated view on dynamic changes during dexamethasone-induced atrophy in the widely used murine skeletal muscle cell line C2C12. Comparison with published mouse data confirmed that muscle differentiation is well recapitulated in C2C12 myotubes. Under dexamethasone treatment, this model was particularly suited to capture early atrophy events. We additionally identified alterations in mitochondrial gene expression and differential alternative splicing events during early-stage myotube atrophy. This dataset complements existing in vivo data and provides novel insights into the regulatory processes during skeletal muscle wasting.NEW & NOTEWORTHY Skeletal muscle atrophy studies rely on in vivo mouse data as well as in vitro data. Our deep coverage transcriptome and proteome data reveal that the commonly used C2C12 cells faithfully recapitulate differentiation and atrophy markers, with significant alternative splicing occurring under dexamethasone atrophy. Using published mouse tissue data of comparable methods, we provide an up-to-date resource for skeletal muscle atrophy to complement animal studies.