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Single-cell RNA-seq reveals the role of YAP1 in prefrontal cortex microglia in depression
Fenghui Ma1, Hongjun Bian2, Wenyan Jiao3
1Department of Health Management, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
This study reveals YAP1 as a key molecule in microglia dysfunction contributing to depression. Elevated YAP1 in the prefrontal cortex correlates with depression severity, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Depression involves complex molecular pathways and brain regions like the prefrontal cortex.
- Microglia, the brain's immune cells, are implicated in depression pathogenesis due to their altered states.
- Understanding microglia's role is crucial for novel depression treatments.
Purpose of the Study:
- To investigate the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression using single-cell RNA sequencing.
- To identify key molecular players and pathways involved in microglia dysfunction in depression.
- To explore YAP1 as a potential biomarker and therapeutic target for depression.
Main Methods:
- Single-cell RNA sequencing of human and rhesus monkey prefrontal cortex tissues.
- Microglia sub-clustering, differential gene expression, KEGG pathway, and intercellular interaction analyses.
- Bulk RNA-Seq, WGCNA, and clinical sample validation to confirm YAP1's role in depression.
Main Results:
- Significant alterations in microglia proportion and transcriptional profiles were observed in depressed prefrontal cortex.
- YAP1 was identified as a key molecule elevated in depression, correlating positively with HAMD scores.
- Multiple microglia subpopulations and associated depression-related pathways were elucidated.
Conclusions:
- Single-cell RNA-seq revealed YAP1's pathogenic role in prefrontal cortex microglia in depression.
- Findings provide new insights into depression pathophysiology and identify potential therapeutic targets.
- YAP1 emerges as a potential biomarker for depression onset prediction.
