本项目聚焦的科学问题骨骼肌成体干细胞激活过程中，细胞代谢和蛋白质合成如何形成网络调控骨骼肌成体干细胞激活的分子机制。拟解决的具体科学问题是：骨骼肌成体干细胞激活过程中，多胺代谢产生的亚精胺（Spermidine）通过Hypusine修饰eIF5a在翻译水平调控骨骼肌成体干细胞的激活。本项目的核心研究内容包括：首先，利用特异性敲除eIF5a小鼠、eIF5a转基因小鼠和eIF5aK50A转基因小鼠进一步确定代谢小分子Spermidine通过Hypusine修饰eIF5a调控骨骼肌成体干细胞蛋白质翻译从而影响骨骼肌成体干细胞激活。进一步利用蛋白质组学和多聚核糖体组分分离并测序揭示eIF5a在骨骼肌成体干细胞激活过程中选择性翻译了哪些蛋白，及其分子机制，最后，验证Spermidine是否能够通过促进骨骼肌成体干细胞的激活从而缓解骨骼肌疾病小鼠模型MDX的表型。

Adult stem cells (ASCs) possess the remarkable capacity to self-renew while remaining poised to activation. This ability is controlled by complex programs which are dynamically orchestrated at different steps including metabolism and translation. However, how the metabolism and translational control coordinately regulated stem cell activation is unknown. Using skeletal muscle stem cell activation system, we have recently found spermidine, metabolites of polyamine metabolism, translational control muscle stem cell activation by hypusine of eIF5a. In this project, we will further confirm that spermidine mediated hypusine of eIF5a is required for the activation of muscle stem cell by using muscle specific eIF5a knockout mice, eIF5a TG and eIF5aK50A TG mice. By Proteomics and Polysome fraction RNA seq, we will explore the mechanism of hypusine eIF5a mediated translational control. Finally, we will verify whether spermidine ameliorate mdx mice by promoting muscle stem cell activation.