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01 14, 2020;10 (1): 229.

Single-cell transcriptional profiles in human skeletal muscle.

Aliza B Rubenstein, Gregory R Smith, Ulrika Raue, Gwénaëlle Begue, Kiril Minchev, Frederique Ruf-Zamojski, Venugopalan D Nair, Xingyu Wang, Lan Zhou, Elena Zaslavsky, Todd A Trappe, Scott Trappe, Stuart C Sealfon
Author Information
  1. Aliza B Rubenstein: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA.
  2. Gregory R Smith: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA.
  3. Ulrika Raue: Human Performance Laboratory, Ball State University, Muncie, Indiana, 47306, USA.
  4. Gwénaëlle Begue: Human Performance Laboratory, Ball State University, Muncie, Indiana, 47306, USA. ORCID
  5. Kiril Minchev: Human Performance Laboratory, Ball State University, Muncie, Indiana, 47306, USA.
  6. Frederique Ruf-Zamojski: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. ORCID
  7. Venugopalan D Nair: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA.
  8. Xingyu Wang: Department of Neurology, Boston University Medical Center, Boston, MA, 02118, USA.
  9. Lan Zhou: Department of Neurology, Boston University Medical Center, Boston, MA, 02118, USA.
  10. Elena Zaslavsky: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. ORCID
  11. Todd A Trappe: Human Performance Laboratory, Ball State University, Muncie, Indiana, 47306, USA.
  12. Scott Trappe: Human Performance Laboratory, Ball State University, Muncie, Indiana, 47306, USA.
  13. Stuart C Sealfon: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. stuart.sealfon@mssm.edu. ORCID
PMID: 31937892 DOI: 10.1038/s41598-019-57110-6

Abstract

Skeletal muscle is a heterogeneous tissue comprised of muscle fiber and mononuclear cell types that, in addition to movement, influences immunity, metabolism and cognition. We investigated the gene expression patterns of skeletal muscle cells using RNA-seq of subtype-pooled single human muscle fibers and single cell RNA-seq of mononuclear cells from human vastus lateralis, mouse quadriceps, and mouse diaphragm. We identified 11 human skeletal muscle mononuclear cell types, including two fibro-adipogenic progenitor (FAP) cell subtypes. The human FBN1+ FAP cell subtype is novel and a corresponding FBN1+ FAP cell type was also found in single cell RNA-seq analysis in mouse. Transcriptome exercise studies using bulk tissue analysis do not resolve changes in individual cell-type proportion or gene expression. The cell-type gene signatures provide the means to use computational methods to identify cell-type level changes in bulk studies. As an example, we analyzed public transcriptome data from an exercise training study and revealed significant changes in specific mononuclear cell-type proportions related to age, sex, acute exercise and training. Our single-cell expression map of skeletal muscle cell types will further the understanding of the diverse effects of exercise and the pathophysiology of muscle disease.

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Grants

  1. R01 AR074428/NIAMS NIH HHS
  2. U24 DK112331/NIDDK NIH HHS

MeSH Term

Adipogenesis
Animals
Biomarkers
Diaphragm
Female
Humans
Male
Mice
Muscle, Skeletal
Quadriceps Muscle
Single-Cell Analysis
Transcriptome

Chemicals

Biomarkers
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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