Single-cell transcriptional profiles in human skeletal muscle

Skeletal muscle is a complex heterogeneous tissue comprised of diverse muscle fiber and non-fiber cell types that, in addition to movement, influences other systems such as immunity, metabolism and cognition. We investigated gene expression patterns of resident human skeletal muscle cells using single-cell RNA-seq of dissections from vastus lateralis. We generate transcriptome profiles of 11 mononuclear human skeletal muscle mononuclear cell types, including immune, endothelial, pericyte and satellite cells.  We delineate two fibro-adipogenic progenitor cell subtypes that may contribute to heterotopic ossification and muscular dystrophy fibrosis under pathological conditions. An important application of cell type signatures is for computational deconvolution of cell type specific changes using data from bulk transcriptome experiments. Analysis of transcriptome data from a 12 week resistance training study using the human skeletal muscle cell-type signatures revealed significant changes in specific mononuclear cell-type proportions related to age, sex, acute exercise and training. This characterization of human skeletal muscle cell subtypes will resolve cell type specific changes in large-scale physical activity muscle transcriptome studies and can further the understanding of the diverse effects of exercise and the pathophysiology of muscle disease. Single cell RNA sequencing was conducted on four samples of mononuclear muscle cells isolated from a single vastus lateralis biopsy.