Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells 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 (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC 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 Hu-MuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ Hu-MuSCs are morphologically distinct, and characterized by resistance to activation compared to CAV1- Hu-MuSCs. In vivo, CAV1+ Hu-MuSCs demonstrated increased engraftment after transplantation. Our findings provide a comprehensive transcriptional view of normal Hu-MuSCs and describe new heterogeneity, enabling separation of functionally distinct human satellite cell subpopulations.
Single cell rna sequencing data were uploaded to Dryad and can be accessed under the doi: 10.7272/Q65X273X
Functionally heterogeneous human satellite cells identified by single cell RNA sequencingDryad Digital Repository, 10.7272/Q65X273X.
- Jason H Pomerantz
- Jason H Pomerantz
- Steven M Garcia
- Solomon Lee
- Alvin Wong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All procedures were approved and performed in accordance with the UCSF Institutional Animal Care and Use Committee (Protocols #181101).
Human subjects: This study was conducted under the approval of the Institutional Review Board at The University of California San Francisco (UCSF). Written informed consent was obtained from all subjects.
- Shahragim Tajbakhsh, Institut Pasteur, France
© 2020, Barruet et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.