Wu YongHong, Xie Lei, Sun Jing, Wang Qing, Xia WangXiao, Cai Qiang, Lu XiaoYun, Gou XingChun
School of Medical Technology & Institute of Basic Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi Province 710021, China; Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi Province 710049, China.
Department of Radiology, Cancer Hospital of Shantou University Medical College, Shantou City, Guangdong Province 515041, China.
Brain Res Bull. 2025 Jun 15;226:111355. doi: 10.1016/j.brainresbull.2025.111355. Epub 2025 Apr 24.
Astrocytes play a key role in the occurrence and development of ischemic stroke. However, reactive astrocytes have both detrimental and protective roles in ischemic stroke. Regrettably, the stimulation signals associated with the transformation of astrocytes into different subclusters lack systemic analysis, and the mechanism by which astrocytes produce multiple effects is not entirely clear. We investigated the heterogeneity of mouse astrocytes 12 h after cerebral ischemia-reperfusion via Single-cell RNA sequencing and verified gene expressions by reverse transcription-polymerase chain reaction. We acquired astrocyte subclusters' transcriptional characteristics involved in diversified functions. To explore what stimulus signals cause astrocyte heterogeneity, we present a blueprint for cellular communication between astrocyte subclusters and other surrounding brain cells 12 h after ischemia-reperfusion, and identified 9 genes which are potential and promising for being therapeutic targets and 6 genes were specific to astrocyte subcluster 2 that tend to resist ischemia-reperfusion injury. At 12 h after ischemia-reperfusion, each subcluster of astrocytes is characteristic in terms of function and communication with surrounding cells, which is based on the activation genes and transcription molecules that we have revealed with subcluster characteristics. Our results provide a basis for revealing the anti-injury response of astrocytes to cerebral ischemia-reperfusion, which involves coordination of different subclusters and the coordination of astrocytes with surrounding brain cells.
星形胶质细胞在缺血性脑卒中的发生和发展中起关键作用。然而，反应性星形胶质细胞在缺血性脑卒中中既有有害作用，也有保护作用。遗憾的是，与星形胶质细胞转变为不同亚群相关的刺激信号缺乏系统分析，星形胶质细胞产生多种作用的机制也不完全清楚。我们通过单细胞RNA测序研究了小鼠脑缺血再灌注12小时后星形胶质细胞的异质性，并通过逆转录-聚合酶链反应验证基因表达。我们获得了参与多种功能的星形胶质细胞亚群的转录特征。为了探究哪些刺激信号导致星形胶质细胞异质性，我们给出了缺血再灌注12小时后星形胶质细胞亚群与其他周围脑细胞之间细胞通讯的蓝图，并鉴定出9个有潜力成为治疗靶点的基因以及6个对倾向于抵抗缺血再灌注损伤的星形胶质细胞亚群2具有特异性的基因。在缺血再灌注12小时后，星形胶质细胞的每个亚群在功能以及与周围细胞的通讯方面都具有特征，这是基于我们通过亚群特征揭示的激活基因和转录分子。我们的结果为揭示星形胶质细胞对脑缺血再灌注的抗损伤反应提供了依据，这涉及不同亚群之间的协调以及星形胶质细胞与周围脑细胞的协调。
