Objective UC is a chronic inflammatory disease of the colonic mucosa. Growing evidence supports a role for epithelial cell defects in driving pathology. Moreover, long-lasting changes in the epithelial barrier have been reported in quiescent UC. Our aim was to investigate whether epithelial cell defects could originate from changes in the epithelial compartment imprinted by the disease. Design Epithelial organoid cultures (EpOCs) were expanded ex vivo from the intestinal crypts of non-IBD controls and patients with UC. EpOCs were induced to differentiate (d-EpOCs), and the total RNA was extracted for microarray and quantitative real-time PCR (qPCR) analyses. Whole intestinal samples were used to determine mRNA expression by qPCR, or protein localisation by immunostaining. Results EpOCs from patients with UC maintained self-renewal potential and the capability to give rise to differentiated epithelial cell lineages comparable with control EpOCs. Nonetheless, a group of genes was differentially regulated in the EpOCs and d-EpOCs of patients with UC, including genes associated with antimicrobial defence (ie, LYZ, PLA2G2A), with secretory (ie, ZG16, CLCA1) and absorptive (ie, AQP8, MUC12) functions, and with a gastric phenotype (ie, ANXA10, CLDN18 and LYZ). A high rate of concordance was found in the expression profiles of the organoid cultures and whole colonic tissues from patients with UC. Conclusions Permanent changes in the colonic epithelium of patients with UC could be promoted by alterations imprinted in the stem cell compartment. These changes may contribute to perpetuation of the disease.

中文翻译：

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上皮干细胞室的改变可能导致溃疡性结肠炎患者粘膜的永久性变化

目的UC是一种结肠黏膜的慢性炎症性疾病。越来越多的证据支持上皮细胞缺陷在驱动病理学中的作用。此外，已经报道了静止 UC 中上皮屏障的长期变化。我们的目的是调查上皮细胞缺陷是否可能源于疾病印记的上皮区室的变化。设计 上皮类器官培养物 (EpOCs) 从非 IBD 对照组和 UC 患者的肠道隐窝中体外扩增。EpOCs 被诱导分化 (d-EpOCs)，提取总 RNA 用于微阵列和定量实时 PCR (qPCR) 分析。全肠样本用于通过 qPCR 确定 mRNA 表达，或通过免疫染色确定蛋白质定位。结果 UC 患者的 EpOCs 保持了自我更新的潜力和产生与对照 EpOCs 相当的分化上皮细胞谱系的能力。尽管如此，一组基因在 UC 患者的 EpOCs 和 d-EpOCs 中受到差异调节，包括与抗菌防御相关的基因（即 LYZ、PLA2G2A）、分泌性（即 ZG16、CLCA1）和吸收性（即 AQP8 , MUC12) 起作用，并具有胃表型（即 ANXA10、CLDN18 和 LYZ）。在来自 UC 患者的类器官培养物和整个结肠组织的表达谱中发现了很高的一致性。结论 UC 患者结肠上皮的永久性变化可以通过印在干细胞室中的改变来促进。这些变化可能会导致疾病的持续存在。