Single cell dynamics of embryonic muscle progenitor cells in zebrafish

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 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 during both normal muscle growth as well as muscle regeneration. 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 and generate 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.