Single-Cell Transcriptomic Landscape of Chronic Enteropathy Associated with SLCO2A1

Chronic enteropathy associated with SLCO2A1 (CEAS) is a rare monogenic disorder characterized by intestinal ulceration and fibrostenosis, yet its underlying mechanisms remain unclear. Here, we constructed the first single-cell transcriptomic map of CEAS using intestinal samples from six genetically confirmed patients. The analysis revealed marked expansion of stromal populations, including a CEAS-specific endothelial subcluster with dysregulated angiogenesis activity. Pseudotime analyses identified a differentiation blockade between capillary and venous endothelial states. Functional experiments confirmed that SLCO2A1 knockdown under prostaglandin imbalance promoted abnormal, immature angiogenesis in vitro. Crosstalk analysis highlighted the involvement of epithelial-stromal signaling via the HIF1-VEGFA-PTGS2 axis, and drug prediction identified candidate therapies including VEGFA and JAK inhibitors. Together, these findings define endothelial dysfunction as a central driver of CEAS and suggest novel therapeutic avenues.