A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations

Skelet Muscle. 2020 Jul 6;10(1):19. doi: 10.1186/s13395-020-00236-3.

Abstract

Single-cell RNA-sequencing (scRNA-seq) facilitates the unbiased reconstruction of multicellular tissue systems in health and disease. Here, we present a curated scRNA-seq dataset of human muscle samples from 10 adult donors with diverse anatomical locations. We integrated ~ 22,000 single-cell transcriptomes using Scanorama to account for technical and biological variation and resolved 16 distinct populations of muscle-resident cells using unsupervised clustering of the data compendium. These cell populations included muscle stem/progenitor cells (MuSCs), which bifurcated into discrete "quiescent" and "early-activated" MuSC subpopulations. Differential expression analysis identified transcriptional profiles altered in the activated MuSCs including genes associated with aging, obesity, diabetes, and impaired muscle regeneration, as well as long non-coding RNAs previously undescribed in human myogenic cells. Further, we modeled ligand-receptor cell-communication interactions and observed enrichment of the TWEAK-FN14 pathway in activated MuSCs, a characteristic signature of muscle wasting diseases. In contrast, the quiescent MuSCs have enhanced expression of the EGFR receptor, a recognized human MuSC marker. This work provides a new benchmark reference resource to examine human muscle tissue heterogeneity and identify potential targets in MuSC diversity and dysregulation in disease contexts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cells, Cultured
  • Cytokine TWEAK / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Profiling / standards*
  • Humans
  • Myoblasts / classification
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Reference Standards
  • Single-Cell Analysis / methods
  • Single-Cell Analysis / standards*
  • TWEAK Receptor / metabolism
  • Transcriptome*

Substances

  • Cytokine TWEAK
  • TWEAK Receptor
  • ErbB Receptors