Single-cell RNA-seq analysis of Mesp1-induced skeletal myogenic development

Biochem Biophys Res Commun. 2019 Dec 3;520(2):284-290. doi: 10.1016/j.bbrc.2019.09.140. Epub 2019 Oct 5.

Abstract

The Mesp1 lineage contributes to cardiac, hematopoietic and skeletal myogenic development. Interestingly, muscle stem cells residing in craniofacial skeletal muscles primarily arise from Mesp1+ progenitors, but those in trunk and limb skeletal muscles do not. To gain insights into the difference between the head and trunk/limb muscle developmental processes, we studied Mesp1+ skeletal myogenic derivatives via single-cell RNA-seq and other strategies. Using a doxycycline-inducible Mesp1-expressing mouse embryonic stem cell line, we found that the development of Mesp1-induced skeletal myogenic progenitors can be characterized by dynamic expression of PDGFRα and VCAM1. Single-cell RNA-seq analysis further revealed the heterogeneous nature of these Mesp1+ derivatives, spanning pluripotent and mesodermal to mesenchymal and skeletal myogenic. We subsequently reconstructed the single-cell trajectories of these subpopulations. Our data thereby provide a cell fate projection of Mesp1-induced skeletal myogenesis.

Keywords: Mesoderm patterning; Mesp1; Myogenic differentiation; Single-cell RNA-Sequencing; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Doxycycline / pharmacology
  • Mice
  • Muscle Development / drug effects
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • RNA-Seq*
  • Single-Cell Analysis*

Substances

  • Anti-Bacterial Agents
  • Basic Helix-Loop-Helix Transcription Factors
  • Mesp1 protein, mouse
  • Doxycycline