The EoE esophageal epithelial transcriptomic landscape
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA904499 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22386700_1.fastq.gz | Fastqsanger.gz | |||
| SRR22386700_2.fastq.gz | Fastqsanger.gz | |||
| SRR22386701_1.fastq.gz | Fastqsanger.gz | |||
| SRR22386701_2.fastq.gz | Fastqsanger.gz | |||
| SRR22386702_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 116 |
Similar Datasets
Project description:We report alterations in the esophageal transcriptome of adult eosinophilic esophagitis (EoE) patients at a single-cell transcriptomic level.
2023-08-07 | GSE218607 | GEO
Project description:Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophageal mucosa. Although type 2 cytokines are predominant, targeting type 2 inflammation alone is not always effective for all patients. In EoE patients, the transcriptional profiling of esophageal biopsy reveals upregulation of type I and II interferon (IFN) response, dysregulated immune signaling, and downregulation of esophageal-specific genes. However, further investigation is needed to examine the gene expression changes in esophageal epithelium because it plays an important role in EoE. To investigate the upregulation of Interferon Stimulated Genes (ISGs) in EoE esophageal epithelium, we isolated epithelial cells from active EoE patients and non-EoE controls. We performed bulk RNA sequencing to analyze the epithelial-specific transcriptome in EoE. Unsupervised hierarchical clustering of the most variable genes differentiated the active EoE biopsies from non-EoE controls. Gene set enrichment analysis identified IFN-γ response as the most significant upregulated pathway.
2024-02-26 | GSE234973 | GEO
Project description:Background: Massive eosinophil infiltration into the esophagus causes subepithelial fibrosis and esophageal stricture in patients with eosinophilic esophagitis (EoE). However, the pathogenesis of esophageal fibrosis remains unclear. Objective: The present study aimed to elucidate the cellular and molecular mechanisms underlying the induction of esophageal fibrosis. Methods: We established a murine model of EoE accompanied by fibrotic responses following long-term intranasal administration of house dust mite (HDM) antigen. Using this murine model, we investigated the characteristics of immune cells infiltrating the fibrotic region of the inflamed esophagus using flow cytometry and histological analyses. We also analyzed the local inflammatory sites in the esophagus of patients with EoE using single-cell RNA sequencing, flow cytometry, and immunohistochemistry.
2024-08-05 | GSE249276 | GEO
Project description:Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophageal mucosa. While type 2 cytokines are predominant, targeting type 2 inflammation alone is not always effective for all patients. In EoE patients, the transcriptional profiling of esophageal biopsy reveal upregulation of type I and II interferon (IFN) response, dysregulated immune signaling and downregulation of esophageal-specific genes in EoE patients. However, the role of interferon signaling during EoE is not fully understood. This study aims to investigate the impact of IFN signaling on esophageal epithelium and elucidate its role in EoE. IFN-γ stimulation of esophageal epithelial cells triggered disruption of tissue differentiation, epithelial barrier integrity and cytotoxicity, which are relevant features of EoE immunopathology. Beyond EoE, our findings offer insights into esophageal disorders which may involve increased IFN-γ signaling, including infections, gastrophageal reflux disease, and Barrett's esophagus.
2024-02-26 | GSE234424 | GEO
Project description:Introduction Disruption of the epithelial barrier can induce eosinophilic esophagitis (EoE), a TH2-mediated food- and aeroallergen associated chronic inflammatory disease 1, 2. The expression of IL-20 subfamily cytokines, IL-19, IL-20 and IL-24, is increased in TH2-mediated diseases, yet their function in EoE is unknown. Methods Combining RNA-sequencing (RNA-seq) and proteome analysis, we have examined the effects of the IL-20 subfamily on esophageal epithelial cells using patient-derived organoids and an experimental EoE mouse model. Results When stimulated with IL-20 subfamily cytokines patient-derived esophageal organoids showed decreased expression of Filaggrin (FLG) and Filaggrin 2 (FLG2) responsible for epithelial cornification. In agreement, EoE patients with active inflammation showed elevated IL-20 subfamily cytokines and decreased FLG and FLG2 expression. Topical corticosteroid treatment in EoE patients restored filaggrin expression, while reducing IL-20 subfamily cytokines. Abolishment of IL-20 subfamily signalling in Il20R2-/- animals attenuated experimental EoE in an OVA-induced mouse model. In the esophageal keratinocyte cell line, KYSE-180, we identified IL-20 subfamily-induced STAT3 and MAPK (ERK1/2) pathway activation. However, Stat3fl/flKrt5cre mice with an epithelium specific deletion of Stat3 developed exacerbated experimental EoE with a pronounced decrease of Flg2. In line, combined stimulation of patient-derived esophageal organoids with IL-20 subfamily cytokines and pharmacological inhibition of STAT3 resulted in aggravated decrease of FLG and FLG2. In addition, pharmacological STAT3 inhibition resulted in reduced transepithelial electrical resistance (TEER) and increased macromolecular flux in patient-derived air liquid interface (ALI) cultures. Whereas, inhibition of the MAPK (ERK1/2) pathway hampered IL-20 subfamily induced TEER reduction and paracellular flux increment. Finally, MAPK (ERK1/2) inhibitor treatment reduced infiltrating CD45+ immune cells in the esophagus and alleviated experimental EoE in mice. Conclusion We discovered a novel regulatory function of the IL-20 subfamily for epithelial barrier integrity. Aberrant IL-20 subfamily signaling disturbs the epithelial barrier function, while abrogation of IL-20 subfamily and ERK1/2 signaling restores epithelial integrity and attenuates experimental EoE. Therefore, we propose that targeting the IL-20 subfamily pathway could present a novel therapeutic strategy for EoE treatment.
2023-05-10 | PXD031509 | Pride
Project description:Esophageal biopsy RNA was isolated from proximal esophageal biopsied RNA from patients with EoE-like inflammatory diseases (EoE-like esophagitis, lymphocytic esophagitis, non-specific esophagitis), patients with active EoE, patients with GERD, and unaffected healthy controls. EoE-like inflammatory disease patients were clinically active at the time when biopsies were taken. None of the patients (EoE-like inflammatory diseases, EoE, GERD and controls) were under anti-eosinophil treatment (including dietary restrictions). The quality of the RNA-seq data was assessed using fastqc v. 0.11.5 1) and RSeQC v. 2.6.4 2). The reads were mapped to the reference genome using HiSat2 v. 2.1.0 3). FeatureCounts v. 1.6.0 4) was used to count the number of reads overlapping with each gene as specified in the genome annotation (Homo_sapiens.GRCh38.94). The Bioconducture package DESeq2 5) was used to test for differential gene expression between the experimental groups. TopGo 6) was used to identify gene ontology terms containing unusually many differentially expressed genes. An interactive Shiny application was set up to facilitate the exploration and visualisation of the RNA-seq results. All analyses were run in R version 3.4.4 (2018-03-15)
2022-02-28 | GSE148381 | GEO
Project description:Distinct subsets of eosinophils are reported in inflammatory and healthy tissues, yet the functions of uniquely specialized eosinophils and the signals that elicit them, particularly in eosinophilic esophagitis (EoE), are not well understood. Herein, we report an ex-vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant pro-inflammatory (IL-13) or pro-fibrotic (TGF-β) cytokines. Our results demonstrate that disease-relevant pro-inflammatory and pro-fibrotic signals present in the esophagus of EoE patients cause distinct profiles of eosinophil activation and gene expression.
2024-11-06 | GSE264591 | GEO
Project description:Eosinophilic esophagitis (EoE) is a T helper type 2 (TH2) cytokine-associated disease charaterized by eosinophil infiltration, epithelial cell hyperplasia and tissue remodeling. Recent studies have highlighted a major contribution for IL-13 in EoE pathogenesis. Paired immunoglobulin-like receptor (PIR)-B is a cell surface immune-inhibitory receptor that is expressed by eosinophils and postulated to regulate eosinophil development and migration. We report that Pirb is upregulated in the esophagus after inducible overexpression of IL-13 (CC10-IL13 Tg mice) and is overexpressed by esophageal eosinophils. CC10-IL13Tg/PirB-/- mice displayed increased esophageal eosinophilia and EoE pahtology, including epithelial cell thickening, fibrosis and angiogenesis, compared with CC10-IL13 Tg/PirB+/+ mice. Transcriptome analysis of primary Pirb+/+ and Prib-/- esophageal eosinophils revealed increased expression of transcripts associated with promoting tissue remodeling in Pirb-/- eosinophils including pro-fibrotic genes, genes promoting epithelial-to-mesenchymal transition (EMT) and genes associated with epithelial growth. These data identify PIR-B as a molecular checkpoint in IL-13-induced eosinophil accumulation and activation, which may serve as a novel target for future therapy in EoE.
2016-05-05 | GSE81135 | GEO
Project description:RNA sequencing analysis of proximal and distal esophageal biopsies from a small cohort of EoE, GERD, and control patients was performed to identify differentially expressed genes.
2018-12-31 | GSE41687 | GEO
Project description:Transcriptomic profiling of esophageal epithelium reveals enrichment of IFN-γ response gene signature during active EoE.
| PRJNA983824 | ENA