Functionally heterogeneous human satellite cells identified by single cell RNA sequencing

Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cell population is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (HuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the HuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals. New surface marker combinations were enriched in transcriptional subclusters, including a subpopulation of HuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ HuSCs are morphologically distinct, and are characterized by resistance to activation compared to CAV1- HuSCs. In vivo, CAV1+ HuSCs demonstrated increased engraftment potential after transplantati...