Department of Health Management, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710000, China.
BMC Neurol. 2024 Jun 7;24(1):191. doi: 10.1186/s12883-024-03685-1.
Depression is a complex mood disorder whose pathogenesis involves multiple cell types and molecular pathways. The prefrontal cortex, as a key brain region for emotional regulation, plays a crucial role in depression. Microglia, as immune cells of the central nervous system, have been closely linked to the development and progression of depression through their dysfunctional states. This study aims to utilize single-cell RNA-seq technology to reveal the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression.
Firstly, we performed cell type identification and differential analysis on normal and depressed prefrontal cortex tissues by mining single-cell RNA-seq datasets from public databases. Focusing on microglia, we conducted sub-clustering, differential gene KEGG enrichment analysis, intercellular interaction analysis, and pseudotime analysis. Additionally, a cross-species analysis was performed to explore the similarities and differences between human and rhesus monkey prefrontal cortex microglia. To validate our findings, we combined bulk RNA-Seq and WGCNA analysis to reveal key genes associated with depression and verified the relationship between YAP1 and depression using clinical samples.
Our study found significant changes in the proportion and transcriptional profiles of microglia in depressed prefrontal cortex tissues. Further analysis revealed multiple subpopulations of microglia and their associated differential genes and signaling pathways related to depression. YAP1 was identified as a key molecule contributing to the development of depression and was significantly elevated in depression patients. Moreover, the expression level of YAP1 was positively correlated with HAMD scores, suggesting its potential as a biomarker for predicting the onset of depression.
This study utilized single-cell RNA-seq technology to reveal the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression, providing a new perspective for a deeper understanding of the pathophysiology of depression and identifying potential targets for developing novel treatment strategies.
抑郁症是一种复杂的情绪障碍，其发病机制涉及多种细胞类型和分子途径。前额皮质作为情绪调节的关键大脑区域，在抑郁症的发生和发展中起着至关重要的作用。小胶质细胞作为中枢神经系统的免疫细胞，通过其功能障碍状态与抑郁症的发生和发展密切相关。本研究旨在利用单细胞 RNA-seq 技术揭示 YAP1 在抑郁症前额皮质小胶质细胞中的致病机制。
首先，我们通过挖掘公共数据库中的单细胞 RNA-seq 数据集，对正常和抑郁前额皮质组织进行细胞类型鉴定和差异分析。聚焦于小胶质细胞，我们进行了亚群聚类、差异基因 KEGG 富集分析、细胞间相互作用分析和伪时间分析。此外，我们进行了跨物种分析，以探索人类和恒河猴前额皮质小胶质细胞之间的相似性和差异性。为了验证我们的发现，我们结合了批量 RNA-Seq 和 WGCNA 分析，以揭示与抑郁症相关的关键基因，并使用临床样本验证了 YAP1 与抑郁症之间的关系。
我们的研究发现，抑郁前额皮质组织中小胶质细胞的比例和转录谱发生了显著变化。进一步的分析揭示了小胶质细胞的多个亚群及其相关的差异基因和与抑郁症相关的信号通路。YAP1 被鉴定为导致抑郁症发生的关键分子，并且在抑郁症患者中显著升高。此外，YAP1 的表达水平与 HAMD 评分呈正相关，提示其作为预测抑郁症发作的生物标志物的潜力。
本研究利用单细胞 RNA-seq 技术揭示了 YAP1 在抑郁症前额皮质小胶质细胞中的致病机制，为深入了解抑郁症的病理生理学提供了新的视角，并确定了潜在的新治疗策略的靶点。
Zotero 插件
