Single Cell and Bulk RNA 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.

纤维化是克罗恩病（Crohn’s disease, CD）的常见并发症，常引发对生物制剂耐药的肠狭窄，往往需要手术干预。本研究旨在探究纤维狭窄性回肠克罗恩病的转录组特征，以深入解析驱动肠道纤维化的生物学与细胞机制。本研究对9名接受手术治疗的克罗恩病患者的回肠切除标本，分别采用批量转录组学与单细胞RNA测序（scRNA-seq）进行分析。差异基因表达与通路富集分析共鉴定出81个差异表达基因（DEGs），相较于非狭窄边缘组织，狭窄组织中64个基因上调、17个基因下调。上调基因与炎症、基质重塑、脂肪生成及细胞应激相关，而下调基因则与上皮屏障完整性有关。机器学习与随机森林模型筛选出包括LY96、GREM1与FGF2等关键预测基因，并通过qPCR验证了上述基因。单细胞RNA测序结果显示，GREM1特异性定位于成纤维细胞，而EHD2与FGF2则在成纤维细胞与内皮细胞中表达。狭窄组织中的内皮细胞意外表达平滑肌相关基因，提示内皮细胞与平滑肌增生之间存在潜在机制关联。本研究全面表征了克罗恩病相关回肠狭窄，明确了失调通路、潜在生物标志物及肠道纤维化的治疗靶点。

搜集汇总

背景与挑战

背景概述

该数据集包含克罗恩病患者的单细胞和批量RNA测序数据，重点研究肠道纤维化的分子机制。通过对9名手术患者的回肠样本分析，发现了81个差异表达基因，并确定了与疾病相关的关键生物标志物和治疗靶点。