Functionally heterogeneous human satellite cells identified by single cell RNA sequencing

被引:89
作者
Barruet, Emilie [1 ,2 ]
Garcia, Steven M. [1 ,2 ]
Striedinger, Katharine [1 ,2 ]
Wu, Jake [1 ,2 ]
Lee, Solomon [1 ,2 ]
Byrnes, Lauren [3 ]
Wong, Alvin [1 ,2 ]
Sun Xuefeng [4 ]
Tamaki, Stanley [1 ,2 ]
Brack, Andrew S. [4 ]
Pomerantz, Jason H. [1 ,2 ]
机构
[1] Univ Calif San Francisco, Program Craniofacial Biol, Div Plast & Reconstruct Surg, Dept Surg,Eli & Edythe Broad Ctr Regenerat Med, San Francisco, CA 94110 USA
[2] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med, Div Plast & Reconstruct Surg, Dept Orofacial Sci,Program Craniofacial Biol, San Francisco, CA 94110 USA
[3] Univ Calif San Francisco, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med, Dept Orthoped Surg, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
STEM-CELLS; SELF-RENEWAL; REVERSIBLE QUIESCENCE; DNA-DAMAGE; MUSCLE; CAVEOLIN-1; EXPRESSION; TRANSPLANTATION; INFLAMMATION; ACTIVATION;
D O I
10.7554/eLife.51576
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:27
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