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Muscle injury induces a transient senescence-like state that is required for myofiber growth during muscle regeneration
Laura V Young 1, Griffen Wakelin 1, Alasdair W R Cameron 1, Stevan A Springer 1, Joel P Ross 1, Grant Wolters 1, J Patrick Murphy 1, Michel G Arsenault 1, Sean Ng 2, Nicolás Collao 3, Michael De Lisio 3, Vladimir Ljubicic 2, Adam P W Johnston 1 4 5
...Here, we use spatial transcriptomics and single-cell RNA sequencing (scRNAseq) to demonstrate that cells displaying senescent characteristics are "transiently" present within regenerating skeletal muscle and within the muscles of D2-mdx mice, a model of Muscular Dystrophy. Following injury, multiple cell types including macrophages and fibrog-adipogenic progenitors (FAPs) upregulate senescent features such as senescence pathway genes, SASP factors, and senescence-associated beta-gal (SA-β-gal) activity. Importantly, when these cells were removed with ABT-263, a senolytic compound, satellite cells are reduced, and muscle fibers were impaired in growth and myonuclear accretion. These results highlight that an "acute" senescent phenotype facilitates regeneration similar to skin and neonatal myocardium.