随着中国人口老龄化趋势逐渐明显，衰老及相关疾病相关机制研究日趋迫切。目前关于表观遗传学因子，特别是长度约50-250nt的核仁小RNA（snoRNA）分子，对HSC衰老的精密调控作用与机制仍缺乏深入的研究。本研究组前期工作发现衰老小鼠中HSC数目增加、端粒变短，衰老HSC中端粒维持信号通路基因显著下调。之前文献报道，H/ACA类型snoRNA分子通过靶向端粒酶复合物中RNA成员TERC来影响端粒长度与功能，进而通过小片段非编码RNA测序鉴定出衰老HSC中snoRNA分子的特异表达谱。本课题拟通过假尿苷酸测序等技术和snoRNA基因敲除小鼠，探索snoRNA分子通过影响端粒酶RNA假尿苷酸化修饰调控HSC衰老的分子机制。本研究对于揭示snoRNA分子调控HSC衰老的作用及详细机制具有重要意义，为理解HSC衰老及相关疾病机制提供新的视角和理论基础。

With China moving towards an aging society, researches on aging and related diseases are becoming an urgent issue. Currently, understanding the roles of epigenetic regulators in HSC aging, especially the small nucleolar RNAs (snoRNA) of 50~250 nt in length, are still needed. Our preliminary work demonstrated that number of HSCs decreases and telomere length shortens in aged mice, and gene expression levels of telomere maintenance signaling pathways are significantly reduced. Previous studies have shown that box H/ACA snoRNAs could regulate the length and functionality of telomeres by targeting telomerase RNA component (TERC). Exploiting high through-put small non-coding RNA sequencing technology, we identified snoRNAs which are specifically expressed in aged HSCs. In this study, by use of advanced technologies including pseudouridylation profiling and genetically knockout mice, we will explore the roles and underlying mechanisms how box H/ACA snoRNAs regulate HSC aging by modifying pseudouridylation in TERC. Our work will demonstrate the roles and underlying epigenetic mechanisms of snoRNAs in HSC aging, and provide new insights into the regulation of HSC aging and aging-related diseases.