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

背景：支配肌肉适应和修复的过程非常复杂，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。其中许多相互作用/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毛细血管等其他结构之间的特定关系在调节卫星细胞功能方面是否重要。此外，尽管卫星细胞被认为是骨骼肌中的主要干细胞群体，但在啮齿类动物中，有证据表明存在其他干祖细胞群体，这些群体甚至从未在人类骨骼肌中被描述过，但仍可能在支持骨骼肌生长和适应方面发挥重要作用。目的：1.研究肌肉卫星细胞、肌纤维毛细血管与骨骼肌适应/修复的关系。2.鉴定和鉴定静息和急、慢性运动后骨骼肌中的一种新的干细胞群。PW1间质细胞(PICS)在啮齿类动物中已被描述，在解剖学和功能上不同于卫星细胞，但已被证明参与肌肉再生的效率与卫星细胞相同。最近，我们首次在人类骨骼肌中发现了PICS。科学方法：利用健康人体的刺激反应研究以及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。我们相信，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。我们还将描述人类骨骼肌中PICS人群的特征，我们将检查对单次破坏性运动的急性反应以及对运动训练范式的慢性反应，以充分描述休息、急性运动和训练后的PICS人群的特征。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修复/适应/生长以响应特定刺激的新知识。

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.