A myogenin+/CD74+ adult muscle stem cell population during regeneration of skeletal muscle lacking miR-501

Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells to address this question. Single-cell sequencing revealed a novel subpopulation of committed myogenic progenitor cells in miR-501 knockout mice that express high levels of terminal differentiation markers and inflammatory genes such as CD74. Our data show that stem cell heterogeneity in skeletal muscle during ageing is under miRNA control. Overall design: We performed genome-wide identification of differentially expressed genes upon genetic deletion of miR-501. For each run, 3 Pax7Cre and 3 Pax7CremiR-501fl/Y (miR-501KO) mice were subjected to cardiotoxin-induced muscle regeneration. On day 6, the skeletal muscle resident stem cells called myogenic progenitors were FACS-sorted and immediately processed for single-cell sequencing. For data analysis, two independent experiments were merged, creating a dataset of 6 miR-501KO mice vs. 6 control littermates.