Functionally heterogeneous human satellite cells identified by single cell RNA sequencing

被引:90
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
相关论文
共 107 条
[71]   Self-renewal and expansion of single transplanted muscle stem cells [J].
Sacco, Alessandra ;
Doyonnas, Regis ;
Kraft, Peggy ;
Vitorovic, Stefan ;
Blau, Helen M. .
NATURE, 2008, 456 (7221) :502-506
[72]   Spatial reconstruction of single-cell gene expression data [J].
Satija, Rahul ;
Farrell, Jeffrey A. ;
Gennert, David ;
Schier, Alexander F. ;
Regev, Aviv .
NATURE BIOTECHNOLOGY, 2015, 33 (05) :495-U206
[73]   Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress [J].
Scaramozza, Annarita ;
Park, Dongsu ;
Kollu, Swapna ;
Beerman, Isabel ;
Sun, Xuefeng ;
Rossi, Derrick J. ;
Lin, Charles P. ;
Scadden, David T. ;
Crist, Colin ;
Brack, Andrew S. .
CELL STEM CELL, 2019, 24 (06) :944-+
[74]   Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models [J].
Schiaffino, Stefano ;
Mammucari, Cristina .
SKELETAL MUSCLE, 2011, 1
[75]   Sox8 is a specific marker for muscle satellite cells and inhibits myogenesis [J].
Schmidt, K ;
Glaser, G ;
Wernig, A ;
Wegner, M ;
Rosorius, O .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (32) :29769-29775
[76]   Interferon-γ:: an overview of signals, mechanisms and functions [J].
Schroder, K ;
Hertzog, PJ ;
Ravasi, T ;
Hume, DA .
JOURNAL OF LEUKOCYTE BIOLOGY, 2004, 75 (02) :163-189
[77]   Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration [J].
Shea, Kelly L. ;
Xiang, Wanyi ;
LaPorta, Vincent S. ;
Licht, Jonathan D. ;
Keller, Charles ;
Basson, M. Albert ;
Brack, Andrew S. .
CELL STEM CELL, 2010, 6 (02) :117-129
[78]   Annexin A1: Uncovering the Many Talents of an Old Protein [J].
Sheikh, Madeeha H. ;
Solito, Egle .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (04)
[79]   Tyrosine phosphorylation of VE-cadherin and claudin-5 is associated with TGF-β1-induced permeability of centrally derived vascular endothelium [J].
Shen, Weiyong ;
Li, Shiying ;
Chung, Sook Hyun ;
Zhu, Ling ;
Stayt, Jason ;
Su, Tao ;
Couraud, Pierre-Olivier ;
Romero, Ignacio A. ;
Weksler, Babette ;
Gillies, Mark C. .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2011, 90 (04) :323-332
[80]   Isolation of adult mouse myogenic progenitors: Functional heterogeneity of cells within and engrafting skeletal muscle [J].
Sherwood, RI ;
Christensen, JL ;
Conboy, IM ;
Conboy, MJ ;
Rando, TA ;
Weissman, IL ;
Wagers, AJ .
CELL, 2004, 119 (04) :543-554