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斑马鱼胚胎肌肉祖细胞的单细胞动态。

Single cell dynamics of embryonic muscle progenitor cells in zebrafish.

机构信息

Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive, Calgary, AB T2N 4N1, Canada.

Inflammation Research Network, The Snyder Institute for Chronic Diseases, Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, Calgary, AB T2N 4N1, Canada.

出版信息

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 behavior of muscle stem cells during muscle growth and regeneration is still poorly understood. Using zebrafish as a model, we describe the 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 (). Utilizing a new transgenic line, we show that MPCs display a ramified morphology with dynamic cellular processes. Cell lineage tracing demonstrates that 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 MPCs change from the quiescent ramified morphology to a polarized and elongated morphology, generating daughter cells that fuse with existing myofibers. Partial depletion of MPCs severely compromises muscle regeneration. Our work provides a dynamic view of embryonic muscle progenitor cells during zebrafish muscle growth and regeneration.

摘要

肌肉干细胞在修复受损肌肉方面具有巨大的治疗潜力。然而,肌肉干细胞在肌肉生长和再生过程中的行为仍知之甚少。我们以斑马鱼为模型,描述了真皮肌节中胚胎肌肉祖细胞(MPC)的动态和功能。这些细胞位于肌肉纤维外部的浅层,表达许多细胞外基质(ECM)基因,包括 ()。利用一种新的转基因系,我们发现 MPC 呈现出分支形态,具有动态的细胞过程。细胞谱系追踪表明,MPC 有助于正常肌肉生长和肌肉再生过程中的新肌纤维形成。活细胞成像和单细胞克隆分析的组合揭示了肌肉再生的高度协调过程。激活的 MPC 从静止的分支形态转变为极化和伸长的形态,产生与现有肌纤维融合的子细胞。MPC 的部分耗竭严重影响肌肉再生。我们的工作提供了斑马鱼肌肉生长和再生过程中胚胎肌肉祖细胞的动态视图。

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