Satellite cell heterogeneity for proinflammatory chemokine expression

The expression of proinflammatory signals at the site of muscle injury are essential for efficient tissue repair and their dysregulation can lead to inflammatory myopathies. In these studies, we examined the contribution of satellite cells, the stem cell population of skeletal muscle, to proinflammatory signaling. Mouse satellite cells in culture express Tnfa, Ccl2, and Il6 within 2 hours of lipopolysaccharide treatment. Single-cell RNA sequencing revealed the satellite cell cultures were heterogeneous, consisting of seven clusters representing the continuum between activation and differentiation. Lipopolysaccharide treatment led to transcription of a broad profile of the C-C and C-X-C chemokines (eg. Ccl2, Ccl5, and Cxcl0) and cytokines (eg. Tgfb1, Bmp2, Il18 and Il33) associated innate immune cell recruitment and satellite cell proliferation. One cell cluster was enriched for genes in the antiviral interferon pathway that could be induced with lipopolysaccharide treatment. Activation of antiviral interferon pathway in satellite cells was also detectable at the site of cardiotoxin induced muscle injury. These data demonstrate that capability of satellite cells are responsive to inflammatory signals to secrete chemokines and cytokines. Further, we identified a novel subset of satellite cells with activated antiviral interferon pathway in the absence of injury or infection. Single-cell RNA-seq of muscle from B6129SF1/J that has either been treated with sham or lipopolysaccharide.