Single Cell Data of IBD patient

Fibrosis, a common complication in Crohn’s disease (CD), frequently leads to intestinal strictures resistant to biologic therapies, necessitating surgical intervention. This study explores the transcriptomic signature of fibrostenotic ileal CD to better understand the biological and cellular mechanisms driving intestinal fibrosis.Resected ileal specimens from nine CD patients undergoing surgery were analyzed using bulk transcriptomics and single-cell RNA sequencing (scRNA-seq). Differential gene expression and pathway enrichment analyses identified 81 differentially expressed genes (DEGs), with 64 up-regulated and 17 down-regulated in strictures compared to non-strictured margins. Up-regulated genes were linked to inflammation, matrix remodeling, adipogenesis, and cellular stress, while down-regulated genes were associated with epithelial barrier integrity. Machine learning and random forest models highlighted key predictive genes, including LY96, GREM1, and FGF2, which were validated via qPCR.scRNA-seq localized GREM1 to fibroblasts, while EHD2 and FGF2 were expressed in fibroblasts and endothelial cells. Endothelial cells in strictures showed unexpected expression of smooth muscle-related genes, suggesting a mechanistic link between endothelial cells and smooth muscle hyperplasia.This study provides a comprehensive characterization of CD-associated ileal strictures, identifying dysregulated pathways, potential biomarkers, and therapeutic targets for intestinal fibrosis.