Satellite cell activation and its paracrine impact on fiber phenotype

卫星细胞激活及其旁分泌对纤维表型的影响

• 批准号: RGPIN-2015-03833
• 负责人: Anderson, Judy
• 金额: $ 3.28万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689094
• 关键词: Satellite; cell; activation; its; paracrine

I explore the fundamental regulation of satellite cells (SC) in muscle; I aim to improve animal-meat production by understanding muscle growth. The known biology of SC, stem cells in muscle, and 2-way SC interactions with muscle fibers and tissues is mostly based on mouse muscle. SC activation to cycle is the first step in growth and regeneration; my explicit focus on that step is nearly unique. Since 2009, I initiated a comparative approach to study SC regulation and activation: we focused on the regulation of zebrafish muscle SC and differences from that of mouse SC, since new findings could be potent if applied to boost aquaculture fish-meat production. The proposed work aims to understand the interplay of SC activity with muscle development, function and regeneration and will advance Canadian innovation capacity in promoting high-quality meat growth in animals. ***My discoveries on chemical, mechanical and protein signals regulating SCs led to studies of muscle growth and muscle-nerve interaction in development and repair; the area is critical to feeding the global population and yet lacks fundamental evidence on SC behaviour. Knowing how outcomes of SC activation are regulated in differential adaptation across species could foster future work by others to design new ways to promote muscle function. My discoveries that SC activation is mediated by nitric oxide and stretch via hepatocyte growth factor, and new collaborative research that implicates SC production of the neuro-repellant protein, Semaphorin3A, in an active, direct regulation of regeneration, underpin the rationale of the proposed research. ***Objectives 1 and 2 address the impact of ectothermy on SC regulation in developing fish species with particular growth modifications: lamprey species have distinct (parasitic or free-living) life-history; ancient sturgeon reach huge size; and zebrafish are available as transgenic strains to test future hypotheses. Local experts are a potent resource to me and HQP as we work to design experiments to discover evolutionarily conserved signals that could ultimately be translated to promote muscle growth and understand functional adaptation. ***Objective 3 extends our exciting discovery that activated SCs make the axon-guidance protein, Semaphorin3A, likely contributing to the functional outcome of new muscle fibers in repair. The novel idea that SCs actively direct other cells in regenerating muscle is unique as most studies see SCs as passive signal receivers; SC signals per se, may shape the capacity for muscle growth and repair. ***My lab is unique in using isolated fibers to study SC activation at the cell level and across species. Basic discoveries from the proposed work will potentially translate knowledge of muscle growth into applications to augment industrial meat production and promote functional regeneration of muscle. **

我探索了肌肉中卫星细胞（SC）的基本调节；我的目标是通过了解肌肉生长来提高动物肉类产量。已知的SC生物学，肌肉中的干细胞，以及SC与肌肉纤维和组织的双向相互作用主要基于小鼠肌肉。SC激活循环是生长和再生的第一步；我对这一步的明确关注几乎是独一无二的。自2009年以来，我发起了一种比较方法来研究SC的调节和激活：我们专注于斑马鱼肌肉SC的调节以及与小鼠SC的差异，因为新的发现可能是有效的，如果应用于提高水产养殖鱼肉产量。拟议的工作旨在了解SC活动与肌肉发育、功能和再生的相互作用，并将提高加拿大在促进动物高质量肉类生长方面的创新能力。***我对调节SCs的化学、机械和蛋白质信号的发现导致了肌肉生长和肌肉-神经在发育和修复中的相互作用的研究；该地区对养活全球人口至关重要，但缺乏关于SC行为的基本证据。了解SC激活的结果是如何在物种间的差异适应中被调节的，可以促进其他人未来设计促进肌肉功能的新方法。我发现SC激活是由一氧化氮介导的，并通过肝细胞生长因子拉伸，新的合作研究表明SC产生神经排斥蛋白Semaphorin3A，在再生的积极，直接调节中，巩固了拟议研究的基本原理。***目标1和2解决了异温性对具有特定生长修饰的发育鱼类的SC调节的影响：七鳃鳗物种具有不同的（寄生或自由生活）生活史；古代鲟鱼长得很大；而且斑马鱼可以作为转基因品种来测试未来的假设。本地专家是我和HQP的有力资源，因为我们致力于设计实验，以发现进化上保守的信号，这些信号最终可以转化为促进肌肉生长和理解功能适应。***目标3扩展了我们令人兴奋的发现，即活化的SCs产生轴突引导蛋白Semaphorin3A，可能有助于修复新肌肉纤维的功能结果。干细胞主动引导其他细胞再生肌肉的新观点是独特的，因为大多数研究认为干细胞是被动的信号接收器；SC信号本身可能塑造肌肉生长和修复的能力。***我的实验室在使用分离纤维在细胞水平和跨物种研究SC激活方面是独一无二的。这项工作的基本发现将有可能将肌肉生长的知识转化为增加工业肉类生产和促进肌肉功能再生的应用。**