转录组学和eqtl揭示了乳糜泻十二指肠内膜的炎症异质性。

IF 4.5 3区 医学 Q1 GENETICS & HEREDITY
Aarón D Ramírez-Sánchez, Stephanie Zühlke, Raúl Aguirre-Gamboa, Martijn Vochteloo, Lude Franke, Knut E A Lundin, Sebo Withoff, Iris H Jonkers
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引用次数: 0

摘要

在乳糜泻(CeD)中,小肠上皮内层(EL)被复杂的自身炎症反应严重破坏,导致上皮内淋巴细胞攻击上皮细胞。为了了解CeD的肠道变化和遗传调控,我们使用RNA-seq和eQTL分析预测细胞类型,研究了十二指肠EL转录组谱的异质性。该研究包括82名患者的十二指肠活检,分为对照组、无麸质饮食治疗组和未治疗组。共鉴定出1 862个差异表达基因,聚类为4组。两组,一组上调细胞周期功能(n = 366),另一组下调消化、跨膜运输和层粘连蛋白途径(n = 543),根据炎症状态定义了三个样本组:非炎症、轻度炎症或严重炎症。其余两组基因富集于免疫(n = 458)和细胞外基质和屏障功能(n = 495),足以将样品分类为其疾病状况。最后,从上皮细胞和免疫细胞中分离eQTL效应,分别鉴定出6个和15个细胞类型介导的eQTL基因。总之,我们确定了在十二指肠EL中表达的基因,这些基因的表达反映了CeD的异质性,可以作为评估CeD状况及其粘膜和免疫状态的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease.

In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD. We identified 1 862 differential expressed genes, which clustered into four sets. Two sets, one upregulated for cell cycle function (n = 366) and one downregulated for digestion, transmembrane transport, and laminin pathways (n = 543), defined three sample groups based on inflammation status: non-inflamed, mild inflammation or severe inflammation. The remaining two sets of genes were enriched for immune (n = 458) and extracellular matrix and barrier functions (n = 495) and were sufficient to classify samples into their disease conditions. Finally, deconvoluting eQTL effects from epithelial and immune cells identified 6 and 15 cell-type-mediated eQTL genes, respectively. In sum, we identified genes expressed in the duodenal EL whose expression reflect heterogeneity in CeD and that may be used as biomarkers to assess CeD condition and its mucosal and immune status.

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来源期刊
Genes and immunity
Genes and immunity 医学-免疫学
CiteScore
8.90
自引率
4.00%
发文量
28
审稿时长
6-12 weeks
期刊介绍: Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.
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