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Gene expression profiles of endothelium, microglia and oligodendrocytes in hippocampus of post-stroke depression rat at single cell resolution
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2024-11-09 , DOI: 10.1038/s41380-024-02810-3
Cai Li, Wentao Li, Wenbin Wei, Qili Chen, Han Gao, Yanqing Zhao, Lingling Zhang, Li Ling, Hao Shen, Yifen Shen, Yihang Shen

Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The presence of expression profiles, intercellular communications and signaling pathways of these three cell populations of PSD displayed a similar but more aggressive appearance with DEPR compared to MCAO and NC. Taken together, this study characterized the specific gene profile of endothelium, microglia and oligodendrocytes of hippocampal PSD by single cell sequencing, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.



中文翻译:


单细胞分辨率中风后抑郁大鼠海马中内皮细胞、小胶质细胞和少突胶质细胞的基因表达谱



中风后抑郁症 (PSD) 是中风后一种常见但严重的精神并发症。然而,对 PSD 的细胞和分子理解仍有待说明。在目前的研究中,我们通过单侧大脑中动脉闭塞 (MCAO) 和慢性应力刺激 (DEPR) 制备了 PSD 大鼠模型 (MD),并分离了海马组织,用于 10x Genomics 铬的单细胞测序。首先,我们确定了与 NC 、 MCAO 和 DEPR 相比,MD 中存在的内皮和小胶质细胞细胞群增加以及少突胶质细胞受损。内皮细胞和小胶质细胞高度可变基因 (HVG) 的丰富功能表明 MD 血脑屏障增强。接下来,分别分析内皮细胞、小胶质细胞和少突胶质细胞的细胞簇,并鉴定具有不同功能的亚型。与 MCAO 和 NC 相比,这三种 PSD 细胞群的表达谱、细胞间通讯和信号通路的存在在 DEPR 中表现出相似但更具侵袭性的外观。综上所述,本研究通过单细胞测序表征了海马 PSD 的内皮、小胶质细胞和少突胶质细胞的特异性基因谱,强调它们之间的串扰,为 PSD 的深入研究机制研究和药物治疗提供理论依据。

更新日期:2024-11-09
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