High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations

Mol Cell. 2019 May 2;74(3):609-621.e6. doi: 10.1016/j.molcel.2019.02.026. Epub 2019 Mar 25.


Adult tissue repair and regeneration require stem-progenitor cells that can self-renew and generate differentiated progeny. Skeletal muscle regenerative capacity relies on muscle satellite cells (MuSCs) and their interplay with different cell types within the niche. However, our understanding of skeletal muscle tissue cellular composition is limited. Here, using a combined approach of single-cell RNA sequencing and mass cytometry, we precisely mapped 10 different mononuclear cell types in adult mouse muscle. We also characterized gene signatures and determined key discriminating markers of each cell type. We identified two previously understudied cell populations in the interstitial compartment. One expresses the transcription factor scleraxis and generated tenocytes in vitro. The second expresses markers of smooth muscle and mesenchymal cells (SMMCs) and, while distinct from MuSCs, exhibited myogenic potential and promoted MuSC engraftment following transplantation. The blueprint presented here yields crucial insights into muscle-resident cell-type identities and can be exploited to study muscle diseases.

Keywords: CyTOF; satellite cells; single-cell RNA-seq; skeletal muscle stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics*
  • Mice
  • Muscle Development / genetics
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Satellite Cells, Skeletal Muscle / cytology*
  • Satellite Cells, Skeletal Muscle / metabolism
  • Single-Cell Analysis
  • Stem Cells / cytology
  • Stem Cells / metabolism