Human muscle stem cell physiology: Characterization, regulation and function.

背景：控制肌肉适应和修复的过程是高度复杂的，涉及多个器官、组织、细胞、亚细胞细胞器和一系列协调的分子信号事件之间的相互作用。许多这些相互作用/事件仍有待阐明。目前尚不清楚卫星细胞如何与环境相互作用以促进适应/修复，也不清楚卫星细胞与其他结构（如毛细血管）之间的特定关系是否在调节卫星细胞功能中起重要作用。此外，尽管卫星细胞被认为是骨骼肌中的主要干细胞群，但在啮齿类动物中有证据表明，存在其他在人类骨骼肌中从未被描述过的干细胞/祖细胞群，但在支持骨骼肌生长和适应方面可能仍然很重要。目的:1。表征肌肉卫星细胞、肌纤维毛细血管与骨骼肌适应/修复之间的关系。2. 在休息和急性和慢性运动后的骨骼肌中识别和表征一种新的干细胞群。PW1间质细胞（PICS）在啮齿类动物中已被描述，在解剖学和功能上与卫星细胞不同，但已被证明与卫星细胞一样有效地参与肌肉再生。我们最近首次在人类骨骼肌中发现了PICS。科学方法：利用健康人的刺激反应研究和专门的技术和研究设计，我们将检查卫星细胞和肌肉毛细血管之间的关系。我们认为，那些毛细化水平最高的人将经历最强劲的急性卫星细胞反应，因此将处于最佳适应的最佳位置。我们还将对人类骨骼肌中的PICS人群进行表征，并将研究对单次破坏性运动的急性反应以及对运动-训练模式的慢性反应，以充分表征急性运动和训练后休息时的PICS人群。意义：这些目标将继续建立在我们已经取得的进展的基础上，并产生关于人类骨骼肌如何在特定刺激下修复/适应/生长的新知识。

BACKGROUND: The processes that govern muscle adaptation and repair are highly complex and involve interactions between multiple organs, tissues, cells, sub cellular organelles and a host of coordinated molecular signaling events. Many of these interactions/events remain to be elucidated. It is not yet clear how satellite cells interact with their environment to promote adaptation/repair or whether specific relationships between satellite cells and other structures, such as capillaries, are important in regulating satellite cell function. Furthermore, although satellite cells are considered to be the primary stem cell population in skeletal muscle there is evidence in rodents suggesting the presence of other stem/progenitor populations that have never even been described in human skeletal muscle, but may nonetheless be important in supporting skeletal muscle growth and adaptation. OBJECTIVES: 1. To characterize the relationships between muscle satellite cells, muscle fiber capillaries and skeletal muscle adaptation/repair. 2. To identify and characterize a novel stem cell population in skeletal muscle at rest and following acute and chronic exercise. PW1 interstitial cells (PICS) has been described in rodents and are anatomically and functionally distinct from satellite cells but have been shown to participate in muscle regeneration as efficiently as satellite cells. For the first time, we recently identified PICS in human skeletal muscle. SCIENTIFIC APPROACH: Using stimulus response studies in healthy humans and specialized techniques and study designs we will examine the relationship between satellite cells and muscle capillaries. We believe those with the highest levels of capillarization will experience the most robust acute satellite cell response and will therefore, be best positioned for optimal adaptation. We will also characterize the PICS population in human skeletal muscle and we will examine the acute responses to single bouts of damaging exercise as well as the chronic responses to exercise-training paradigms to fully characterize the PICS population at rest, following acute exercise and following training. SIGNIFICANCE: These objectives will continue to build upon the progress we have made and generate new knowledge of how human skeletal muscle can repair/adapt/grow in response to a specific stimulus.