Functionally heterogeneous human satellite cells identified by single cell RNA sequencing.

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Publication Year:
2020
Authors:
Emilie Barruet, Steven M Garcia, Katharine Striedinger, Jake Wu, Solomon Lee, Lauren Byrnes, Alvin Wong, Sun Xuefeng, Stanley Tamaki, Andrew S Brack, Jason H Pomerantz
PubMed ID:
32234209
Funding Grants:
Public Summary:
A comprehensive understanding of distinct subpopulations of human muscle stem cells and their functional relevance is lacking. We used biopsies of normal human muscle samples to analyze the individual muscle stem cells that are present in healthy human muscle. Our findings provide a comprehensive view of genes expressed by normal human muscle stem cells and describe their heterogeneity, enabling separation of functionally distinct human muscle stem cell subpopulations.
Scientific Abstract:
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.