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.
statement: 25 Live imaging and single cell clonal analysis reveal dynamic behaviors of zebrafish embryonic 26 muscle progenitor cells in quiescence and activation. 27 2 ABSTRACT 28 29Muscle stem cells hold a great therapeutic potential in regenerating damaged muscles. 30However, the in vivo behavior of muscle stem cells during muscle growth and regeneration is 31 still poorly understood. Using zebrafish as a model, we describe the in vivo dynamics and 32 function of dermomyotome cells, a population of embryonic muscle progenitor cells. 33Dermomyotome cells are located in a superficial layer external to muscle fibers and express 34 many extracellular matrix (ECM) genes including col1a2. Utilizing a new col1a2 transgenic 35 line, we show that dermomyotome cells display a ramified morphology with dynamic cellular 36 processes. Cell lineage tracing demonstrates that col1a2 + dermomyotome cells contribute to 37 normal muscle growth as well as muscle injury repair. Combination of live imaging and single 38 cell clonal analysis reveals a highly-choreographed process of muscle regeneration. 39Activated dermomyotome cells change from the quiescent ramified morphology to a polarized 40 and elongated morphology and generate daughter cells that fuse with existing muscle fibers. 41
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