Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Katharine Striedinger
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Jake Wu
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Solomon Lee
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Lauren Byrnes
University of California San Francisco, San Francisco, United States
Alvin Wong
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Sun Xuefeng
Department of Orthopedic Surgery, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Stanley Tamaki
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Andrew S Brack
Department of Orthopedic Surgery, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
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.
