The role of nonneuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of the male mouse brain during the first week of injury. Cortical gene expression was severely disrupted, defined by inflammation and cell death in the lesion core, and glial scar formation orchestrated by multiple cell types on the periphery. The glial scar was identified as a zone with intense cell–cell communication, with prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was observed. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. The findings are further supported by analysis of other spatial transcriptomic datasets from different mouse models of ischemic brain injury. Collectively, we present a landmark transcriptomic dataset accompanied by interactive visualization that provides a comprehensive view of spatiotemporal organization of processes in the postischemic mouse brain.

中文翻译：

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急性脑缺血小鼠模型中神经胶质细胞反应的时空转录组图


非神经元细胞在脑缺血消退中的作用仍有待完全了解。为了解码缺血后发生的关键分子和细胞过程，我们在受伤的第一周对雄性小鼠大脑进行了空间和单细胞转录组分析。皮质基因表达严重中断，定义为病变核心的炎症和细胞死亡，以及外围多种细胞类型精心策划的神经胶质瘢痕形成。神经胶质瘢痕被确定为具有强烈细胞间通讯的区域，具有显着的 ApoE-Trem2 信号通路调节小胶质细胞活化。对于三个主要神经胶质细胞群中的每一个，都观察到一种炎症反应状态，类似于在神经退行性环境中观察到的反应状态。缺血诱导的少突胶质细胞状态的恢复谱支持新出现的假设，即少突胶质细胞积极响应和调节神经炎症刺激。来自不同缺血性脑损伤小鼠模型的其他空间转录组数据集的分析进一步支持了这些发现。总的来说，我们提出了一个具有里程碑意义的转录组数据集，并附有交互式可视化，提供了缺血后小鼠大脑过程的时空组织的全面视图。