星形胶质细胞新亚群的发现及其在脑缺血再灌注损伤中的作用及机制

目前星形胶质细胞（As）在脑缺血再灌注（I/R）损伤中的作用备受关注，现有研究发现As形态及功能在不同生理及病理条件下存在明显差异，据此提出了As细胞异质性概念，但该异质性的呈现方式及其在疾病发生中的作用及机制至今不清，因此破译As异质性并阐明其在脑I/R损伤中的作用机制有重要意义。我们前期利用单细胞测序发现As存在五类新细胞亚群，进一步研究显示，脑I/R后皮层高表达LMO1分子的细胞亚群高度聚集，而且LMO1显著上调，强烈提示该新亚群在脑I/R损伤中发挥关键作用。为此本项目拟利用脑I/R模型和临床脑梗死样本，采用转录组、蛋白组学结合生物信息学分析方法，使用基因编辑技术及分子生物学等手段，在探讨高表达LMO1的As新亚群的分子调控网络的基础上，揭示其在脑I/R损伤中的作用及机制。该研究可阐明高表达LMO1的As亚群在脑I/R损伤的作用机制，从As异质性的角度为脑梗死治疗提供新靶点、新思路。

Currently, the role of astrocyte in cerebral ischemia/reperfusion injury has attracted much attention. Researches found that astrocytes have different phenotypes and function in the pathological and physiological conditions, which suggests that astrocytes have obvious heterogeneity. However, the presentation of heterogeneity and its roles under diseases are not clear, therefore, deciphering the astrocyte heterogeneity and its roles in cerebral I/R injury has great significances. Previously, using the single-cell squencing technology, we found that astrocyte has five subgroups. Further analysis found that the subgroup of astrocyte with high expression of LMO1 were highly concentrated in the cerebral cortex after cerebral I/R injury, and the expression of LMO1 was further upregulated, which strongly suggests that this new subgroup of astrocyte may play an important role in the cerebral I/R injury. Accordingly, this project aims at investigating the molecular regulatioin networks of new subgroup of astrocyte with high expression of LMO1 using the cerebral I/R models and clinical samples combing with the transcriptomics, proteomics and bioinformatics, and uncovering the role and mechanisms of this subgroup of astrocyte in cerebral I/R injury. The study could illuminatethe roles and mechanisms of astrocyte with high expression of LMO1 in cerebral I/R injury, and provide new targets and thoughts for the treatment of acute stroke from the view of astrocyte heterogeneity.