Extrinsic Regulation of Muscle Stem Cell Quiescence

肌肉干细胞静止的外在调节

• 批准号: RGPIN-2017-05490
• 负责人: Bentzinger, Florian
• 金额: $ 2.84万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629230
• 关键词: Extrinsic; Regulation; Muscle; Stem; Cell

Stem cells maintaining and repairing adult tissues have a strong dependency on signals provided by the surrounding microenvironment, often referred to as the niche. In skeletal muscle this niche regulation of stem cells is particularly complex and depends on a multitude of different cell types secreting growth factors and instructive extracellular matrix (ECM) in a tightly regulated spatio-temporal manner. Fundamental properties of muscle stem cells (MuSCs), such as quiescence, self-renewal and the ability to differentiate, are determined by the composition of the niche. However, in spite of its important role for the function of MuSCs, the architecture and the instructive signals the niche generates remain incompletely understood. Notably, it remains particularly enigmatic which cellular and extracellular cues in the niche control MuSC quiescence, the important dormant maintenance state that is essential to the life-long ability of mammals to maintain their muscles and recover from injuries. A major focus of our proposed NSERC research program will be to fill this gap in our biological understanding of the niche by studying the microenvironmental regulation of quiescent MuSCs.

维持和修复成体组织的干细胞强烈依赖于周围微环境（通常称为生态位）提供的信号。在骨骼肌中，干细胞的这种生态位调节特别复杂，并且依赖于以严格调节的时空方式分泌生长因子和指导性细胞外基质（ECM）的多种不同细胞类型。肌肉干细胞 (MuSC) 的基本特性，如静止、自我更新和分化能力，是由生态位的组成决定的。然而，尽管它对 MuSC 的功能发挥着重要作用，但其结构和产生的指导信号仍不完全清楚。值得注意的是，生态位中哪些细胞和细胞外信号控制 MuSC 静止状态仍然是特别神秘的，MuSC 静止是一种重要的休眠维持状态，对于哺乳动物终生维持肌肉和从损伤中恢复的能力至关重要。我们提出的 NSERC 研究计划的一个主要重点将是通过研究静态 MuSC 的微环境调节来填补我们对生态位的生物学理解中的这一空白。