Abstract：
Existing research indicates the potential for white matter injury repair during the subacute phase following subarachnoid hemorrhage (SAH). However, elucidating the role of brain cell subpopulations in the acute and subacute phases of SAH pathogenesis remains challenging due to the cellular heterogeneity of the central nervous system. In this study, single-cell RNA sequencing was conducted on SAH model mice to delineate distinct cell populations. Gene Set Enrichment Analysis was performed to identify involved pathways, and cellular interactions were explored using the CellChat package in R software. Validation of the findings involved a comprehensive approach, including magnetic resonance imaging, immunofluorescence double staining, and Western blot analyses. This study identified ten major brain clusters with cell type-specific gene expression patterns. Notably, we observed infiltration and clonal expansion of reparative microglia in white matter-enriched regions during the subacute stage after SAH. Additionally, microglia-associated pleiotrophin (PTN) was identified as having a role in mediating the regulation of oligodendrocyte precursor cells (OPCs) in SAH model mice, implicating the activation of the mTOR signaling pathway. These findings emphasize the vital role of microglia-OPC interactions might occur via the PTN pathway, potentially contributing to white matter repair during the subacute phase after SAH. Our analysis revealed precise transcriptional changes in the acute and subacute phases after SAH, offering insights into the mechanism of SAH and for the development of drugs that target-specific cell subtypes.
摘要：
现有研究表明蛛网膜下腔出血（SAH）后亚急性期白质损伤修复的潜力。然而,由于中枢神经系统的细胞异质性,阐明脑细胞亚群在SAH发病机制急性期和亚急性期中的作用仍然具有挑战性.在这项研究中,对SAH模型小鼠进行单细胞RNA测序以描绘不同的细胞群.进行基因集富集分析以鉴定涉及的途径，使用R软件中的CellChat包探索细胞相互作用。对调查结果的验证涉及一种全面的方法，包括磁共振成像，免疫荧光双重染色，和蛋白质印迹分析。这项研究确定了具有细胞类型特异性基因表达模式的十个主要脑簇。值得注意的是,我们观察到SAH后亚急性期白质富集区修复性小胶质细胞的浸润和克隆性扩增。此外,小胶质细胞相关的多营养蛋白（PTN）被认为在介导SAH模型小鼠少突胶质细胞前体细胞（OPCs）的调节中起作用，涉及mTOR信号通路的激活。这些发现强调了小胶质细胞-OPC相互作用的重要作用可能通过PTN途径发生，可能有助于SAH后亚急性期白质修复。我们的分析揭示了SAH后急性期和亚急性期的精确转录变化，提供对SAH机制的见解和开发靶向特异性细胞亚型的药物。
