成体神经干细胞具有自我更新能力和多分化潜能，受到环境、遗传学和表观遗传学等多种机制在转录、翻译和翻译后水平的精细调控。成体神经干细胞驱动的神经发生在学习记忆和多种神经系统疾病中发挥重要作用。N-乙酰氨基葡萄糖转移酶(Ogt)催化的O-GlcNAc糖基化修饰(O-GlcNAcylation)是一种重要的翻译后修饰形式。O-GlcNAc糖基化修饰不仅对于蛋白质正常发挥功能具有重要作用，而且调控基因表达、信号转导、细胞凋亡和胚胎干细胞的干性维持等多种生物学过程，与癌症、糖尿病和神经退行性病变等疾病密切相关。但是O-GlcNAc糖基化修饰在成体神经干细胞和神经发生中的作用尚不清楚。本项目旨在利用多种实验手段在体内和体外研究O-GlcNAc糖基化修饰对成体神经干细胞生物学特性和神经发生以及学习记忆的调控作用，揭示其作用机制和靶向位点，为相关神经系统疾病的治疗提供新的思路和靶点。

The self-renewal and multipotency of adult neural stem cells (aNSCs) are intensively modulated by environmental, genetic and epigenetic mechanisms at transcriptional, translational and post-translational levels. ANSCs-derived neurogenesis involves in learning and memory, also relates to multiple neurological disorders. O-GlcNAcylation, an important post-translational modification, is catalyzed by O-linked β-N-acetylglucosamine O-GlcNAc transferase (Ogt). O-GlcNAcylation not only plays critical roles in modulating protein function, also involves in regulating gene expression, cell signaling, apoptosis, the maintenance of embryonic stem cells, and other biological processes. The alteration of O-GlcNAcylation has been demonstrated in cancer, diabetes, and neurodegenerative diseases. However, it is largely unknown about the function of O-GlcNAcylation in aNSCs and adult neurogenesis. Utilizing multiple methods, this project aims to study the roles of Ogt-mediated O-GlcNAcylation in regulating aNSCs and adult neurogenesis，and learning and memory, reveal the mechanism, and thus provide novel idea and targets for treating some neurological disorders.