P1295 Transcriptional analysis of chronic enteropathy associated with SLCO2A1 gene at single-cell resolution
Authors: Dong Y , Huang J , Zhang Y , Wang Q , Liu Y , Liu C , Li Y 
Published: January 2025

Abstract

Background
Eight inflamed gastrointestinal tissue samples and one non-inflamed sample from six CEAS patients, along with three healthy controls, were analyzed using single-cell RNA sequencing (scRNA-seq). Cellular composition, transcriptional profiles, and intercellular communication networks were compared to reference datasets, including Crohn’s disease (CD) and ulcerative colitis (UC). SLCO2A1 expression differences across cell types were examined, and pseudotime analysis identified disease-specific transitions. Functional enrichment, cell-cell communication, and in silico drug response analyses uncovered potential therapeutic targets.

Methods
Eight inflamed gastrointestinal tissue samples and one non-inflamed sample from six CEAS patients, along with three healthy samples, were analyzed using single-cell RNA sequencing (scRNA-seq). Cellular composition and transcriptional profiles were compared to reference datasets, including Crohn’s disease (CD) and ulcerative colitis (UC). SLCO2A1 expression differences across cell types were examined, and pseudotime analysis identified disease-specific transitions. Functional enrichment, cell-cell communication, and in silico drug response analyses uncovered potential therapeutic targets.

Results
Our scRNA-seq analysis revealed unique cellular compositions and SLCO2A1 expression patterns in immune, epithelial, and mesenchymal cells in CEAS. Immune cells displayed distinct biases, including reduced pro-inflammatory subsets, while epithelial and mesenchymal cells showed transcriptional changes linked to wound healing and inflammatory signaling, suggesting roles in tissue remodeling. Cell-cell communication analysis revealed that epithelial and mesenchymal cells primarily signaled to endothelial cells via pro-angiogenic factors like VEGFA, positioning endothelial cells as central to CEAS-specific signaling. Endothelial cells, with the highest SLCO2A1 expression, exhibited transcriptional dysregulation, including impaired vascular stability and immune modulation. Pseudotime analysis identified endothelial cell state transitions, implicating SLCO2A1-driven vascular dysfunction as a key driver of CEAS pathogenesis. Potential therapeutic targets were identified in pathways related to prostaglandin metabolism and vascular function.

Conclusion
This study provides a comprehensive single-cell transcriptomic atlas of CEAS, revealing cellular and molecular mechanisms driven by SLCO2A1 variants. Vascular dysfunction emerges as a central driver of CEAS pathogenesis, with implications for inflammation, tissue remodeling, and barrier integrity. These findings offer critical insights into CEAS pathophysiology and inform potential diagnostic and therapeutic strategies targeting SLCO2A1-related pathways.

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