1. Stem Cells and Regenerative Medicine
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Functionally heterogeneous human satellite cells identified by single cell RNA sequencing

Research Article
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Cite this article as: eLife 2020;9:e51576 doi: 10.7554/eLife.51576

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.

Data availability

Single cell rna sequencing data were uploaded to Dryad and can be accessed under the doi: 10.7272/Q65X273X

The following data sets were generated

Article and author information

Author details

  1. Emilie Barruet

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Steven M Garcia

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. 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
    Competing interests
    The authors declare that no competing interests exist.
  4. Jake Wu

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Solomon Lee

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lauren Byrnes

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Alvin Wong

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Sun Xuefeng

    Orthopedic Surgery, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Stanley Tamaki

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Andrew S Brack

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Jason H Pomerantz

    Departments of Surgery and Orofacial Sciences, Division of Plastic Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    For correspondence
    jason.pomerantz@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5107-1883

Funding

California Institute for Regenerative Medicine (New Faculty Physician Scientist Award RN3-06504)

  • Jason H Pomerantz

National Institutes of Health (R01AR072638-03)

  • Jason H Pomerantz

University of California, San Francisco (UCSF PROF-PATH program via NIH R25MD006832)

  • Steven M Garcia

University of California, San Francisco (Research Allocation Program for trainees)

  • Solomon Lee

Eli and Edythe Broad Foundation (Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Fellowship)

  • Alvin Wong

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

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.

Reviewing Editor

  1. Shahragim Tajbakhsh, Institut Pasteur, France

Publication history

  1. Received: September 4, 2019
  2. Accepted: March 27, 2020
  3. Accepted Manuscript published: April 1, 2020 (version 1)
  4. Version of Record published: April 17, 2020 (version 2)

Copyright

© 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.

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