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.

维持和修复成年组织的干细胞对周围微环境提供的信号具有很大的依赖，通常称为利基市场。在骨骼肌中，这种对干细胞的细分调节特别复杂，取决于多种不同的细胞类型，分泌生长因子和具有指导性的细胞外基质（ECM），以严格调节的时空方式。肌肉干细胞（MUSC）的基本特性，例如静止，自我更新和区分能力，取决于利基的组成。然而，尽管它在MUSC的功能中起着重要作用，但构建和启发性信号的利基市场仍未完全理解。值得注意的是，尤其仍然是神秘的，哪些细胞和细胞外提示在小裂控制MUSC静止中，这是重要的休眠维持状态，这对于哺乳动物保持肌肉的终身能力至关重要，并从伤害中恢复。我们拟议的NSERC研究计划的主要重点是通过研究静态MUSC的微环境调节来填补我们对利基市场的生物学理解。