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 transplantation in mice. Our findings provide a
comprehensive transcriptional view of normal HuSCs and describe new
heterogeneity, enabling separation of functionally distinct human
satellite cell subpopulations.