Single-Cell RNA-Sequencing Reveals Cachectic Satellite Cell Population in Muscle of Male Mice With Cancer Cachexia.

backgroundCancer cachexia leads to decreases in body mass, lean mass and fat mass, decreased therapeutic potential and ~20% of cancer-related deaths. While several studies have demonstrated changes to components of the muscle microenvironment with cancer cachexia, none have comprehensively assessed changes to cellular dynamics across the duration of cachexia development.

methodsSingle-cell RNA-sequencing was performed on hindlimb muscles of male mice with 2-, 2.5- and 3.5-week subcutaneous Lewis-lung carcinoma tumours. Cell population changes were confirmed with flow cytometry.

resultsBody mass (-0.51 g; p = 0.0014) and lean mass (-0.85 g; p = 0.0134) were decreased at 2.5 weeks and were significantly lower than sham. Increases in fat mass were attenuated starting at 2 weeks (0.70 g; p = 0.0408) compared to sham (1.55 g), and muscle cross-sectional area decreased at 3.5 weeks (-14.81%; p = 0.0022) compared to sham. We report a novel cachexia-associated satellite cell subcluster, comprising 71.1% of the population at 3.5 weeks, corresponding with a +20.33% increase in cell size (p = 0.0266) and +19.73% increase in the proportion of activated PAX7

conclusionsWe describe a novel satellite cell subcluster unique to cachexia. We also identified increased immune cell and fibroadipogenic progenitor content and decreased endothelial cell content that precede muscle wasting with cancer, suggesting a role for these cell populations in satellite cell dysfunction and muscle atrophy in this condition.