Ischemic stroke (IS) is a detrimental neurological disease with limited treatments options. It has been challenging to define the roles of brain cell subsets in IS onset and progression due to cellular heterogeneity in the CNS. Here, we employed single-cell RNA sequencing (scRNA-seq) to comprehensively map the cell populations in the mouse model of MCAO (middle cerebral artery occlusion). We identified 17 principal brain clusters with cell-type specific gene expression patterns as well as specific cell subpopulations and their functions in various pathways. The CNS inflammation triggered upregulation of key cell type-specific genes unpublished before. Notably, microglia displayed a cell differentiation diversity after stroke among its five distinct subtypes. Importantly, we found the potential trajectory branches of the monocytes/macrophage’s subsets. Finally, we also identified distinct subclusters among brain vasculature cells, ependymal cells and other glia cells. Overall, scRNA-seq revealed the precise transcriptional changes during neuroinflammation at the single-cell level, opening up a new field for exploration of the disease mechanisms and drug discovery in stroke based on the cell-subtype specific molecules.

缺血性中风 (IS) 是一种有害的神经系统疾病，治疗选择有限。由于 CNS 中的细胞异质性，定义脑细胞亚群在 IS 发病和进展中的作用一直具有挑战性。在这里，我们采用单细胞 RNA 测序 (scRNA-seq) 来全面绘制 MCAO（大脑中动脉闭塞）小鼠模型中的细胞群。我们确定了 17 个具有细胞类型特异性基因表达模式以及特定细胞亚群及其在各种途径中的功能的主要脑簇。中枢神经系统炎症引发了以前未发表的关键细胞类型特异性基因的上调。值得注意的是，小胶质细胞在其五种不同的亚型中表现出中风后的细胞分化多样性。重要的，我们发现了单核细胞/巨噬细胞亚群的潜在轨迹分支。最后，我们还在脑血管细胞、室管膜细胞和其他神经胶质细胞中发现了不同的亚群。总体而言，scRNA-seq 在单细胞水平揭示了神经炎症过程中的精确转录变化，为探索基于细胞亚型特异性分子的中风疾病机制和药物发现开辟了新领域。