SATELLITE STEM CELL BIOLOGY

描述(改编自申请人的摘要)：卫星小区 肌肉特异性干细胞，功能是修复受损的肌纤维和 为肌肉扩张提供新的肌核。罗森布拉特已经证明了 敲除卫星细胞的增殖能力可防止肥大 骨骼肌。布劳和赖特发现，卫星细胞过早地 年轻Duchenne肌营养不良症患者的衰老 再生的循环。舒尔茨观察到了一种逐渐丧失的 随着大鼠年龄的增长，卫星细胞的增殖能力，以及类似的数据 刚刚在人类身上被报道过。海弗里克表明，正常的二倍体细胞有一种 有限的增殖寿命，并达到细胞衰老。然而，比肖夫 指出需要对自我维护标准进行严格评价 将卫星细胞归类为干细胞还有待进行。这些 挑衅性的报告强调了一些概念框架，以提出 遵循特定的目标。使用成熟且经过验证的方法 克隆性分析是用来确定细胞的增殖潜力的，这 提案审核1。)一种重复循环的生理模型 陈旧骨骼肌萎缩-再生加速卫星细胞衰老 它们的增殖能力在大鼠寿命之前就已经耗尽； 2.)确定IGF-1是否应用于骨骼肌或3。) 收缩活动增加，或目标1和目标2都会导致a。) 用完或b。)补充旧卫星中的有限种群倍增 细胞。这些结果将为我们提供急需的洞察，了解是否具有复制能力 衰老可以受到环境因素的调节。因此，该信息 这些研究收集到的数据将为后续实验提供依据 这将测量细胞周期标记，以开始解释观察到的 分子细节。随着脆弱个体的数量迅速增加 与日俱增，成为一个更紧迫的临床、社会和经济问题 了解是否以及如何保持/提高卫星电池的寿命。这 因此，该提案将为如何自我维护提供新的见解 卫星细胞的特性受补偿因子(IGF-1和 运动)，从而形成更有效的干预措施的基础 衰老--萎缩和虚弱。

DESCRIPTION (Adapted from the applicant's abstract): Satellite cells are muscle-specific stem cells that function to repair damaged myofibers and provide new myonuclei for muscle enlargement. Rosenblatt has shown that knocking out the proliferative capacity of satellite cells prevents hypertrophy of skeletal muscle. Blau and Wright have found that satellite cells prematurely senesce in young patients with Duchenne's muscular dystrophy who have many cycles of regeneration. Schultz has observed a progressive loss of the proliferative capacity of satellite cells as rats age, and similar data has just been reported in humans. Hayflick showed that normal, diploid cells have a finite proliferative lifespan and reach cellular senescence. However, Bischoff indicated that a critical evaluation of the self-maintenance criteria required to categorize the satellite cell as stem cell is yet to be undertaken. These provocative reports highlight some of the conceptual framework to pose the following specific aims. Using the well-established and validated approach of clonogenecity assays to determine a cell's proliferation potential, this proposal examines 1.) whether a physiological model of repeated cycles of atrophy-regrowth in old skeletal muscle speeds satellite cells to senescence so that their proliferative capacity is depleted prior to the lifespan of rats; 2.) determine whether the application of IGF-1 to skeletal muscle or 3.) increased contractile activity, or both aims 1 and 2 results in either a.) using up or b.) replenishing the finite population doublings in old satellite cells. These results would shed much needed insight into whether replicative senescence can be modulated by environmental factors. The information thus gleaned from these studies will provide the basis for follow-up experiments that will measure cell cycle markers to begin to explain the observations in molecular detail. As the number of individuals with frailty is rapidly increasing, it becomes a more urgent clinical, social, and economic issue to find out if and how satellite cell lifespan can be maintained/enhanced. This proposal will therefore provide novel insights into how the self-maintenance properties of satellite cells is modulated by compensatory factors (IGF-1 and exercise), thereby forming the basis for more effective interventions against senile-atrophy and frailty.