Single cell dynamics of embryonic muscle progenitor cells in zebrafish

Development. 2019 Jul 19;146(14):dev178400. doi: 10.1242/dev.178400.

Abstract

Muscle stem cells hold a great therapeutic potential in regenerating damaged muscles. However, the in vivo behavior of muscle stem cells during muscle growth and regeneration is still poorly understood. Using zebrafish as a model, we describe the in vivo dynamics and function of embryonic muscle progenitor cells (MPCs) in the dermomyotome. These cells are located in a superficial layer external to muscle fibers and express many extracellular matrix (ECM) genes, including collagen type 1 α2 (col1a2). Utilizing a new col1a2 transgenic line, we show that col1a2+ MPCs display a ramified morphology with dynamic cellular processes. Cell lineage tracing demonstrates that col1a2+ MPCs contribute to new myofibers in normal muscle growth and also during muscle regeneration. A combination of live imaging and single cell clonal analysis reveals a highly choreographed process of muscle regeneration. Activated col1a2+ MPCs change from the quiescent ramified morphology to a polarized and elongated morphology, generating daughter cells that fuse with existing myofibers. Partial depletion of col1a2+ MPCs severely compromises muscle regeneration. Our work provides a dynamic view of embryonic muscle progenitor cells during zebrafish muscle growth and regeneration.

Keywords: Dermomyotome; Extracellular matrix; In vivo imaging; Muscle progenitor cells; Somite; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Collagen / genetics
  • Collagen / metabolism
  • Embryo, Nonmammalian
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / physiology
  • Kinetics
  • Muscle Development / physiology
  • Muscle Fibers, Skeletal / physiology
  • Myoblasts / cytology*
  • Myoblasts / physiology*
  • PAX2 Transcription Factor / genetics
  • PAX2 Transcription Factor / metabolism
  • Regeneration / genetics
  • Single-Cell Analysis*
  • Time-Lapse Imaging
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish* / embryology
  • Zebrafish* / physiology

Substances

  • COL1A2 protein, zebrafish
  • PAX2 Transcription Factor
  • Zebrafish Proteins
  • pax7a protein, zebrafish
  • Collagen