Extrinsic Regulation of Muscle Stem Cell Quiescence

维持和修复成体组织的干细胞对周围微环境提供的信号有很强的依赖性，通常被称为生态位。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有益的细胞外基质（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，由小生境的组成决定。然而，尽管其对MuSC的功能具有重要作用，但小生境产生的结构和指导性信号仍然不完全清楚。值得注意的是，它仍然是特别神秘的细胞和细胞外的线索在生态位控制MuSC静止，重要的休眠维持状态，是必不可少的哺乳动物的终身能力，以维持他们的肌肉和从损伤中恢复。我们提出的NSERC研究计划的一个主要重点将是通过研究静止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。

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.