Single-Cell RNA Sequencing Investigation of the Duodenal Mucosa in Canine Chronic Inflammatory Enteropathy and Health
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ABSTRACT: We used single-cell RNA sequencing to characterize the heterogeneity duodenal tissue in healthy and chronic inflammatory enteropathy (CIE) affected dogs.
Project description:A subgroup of CVID patients presents with gastrointestinal complications (enteropathy), which manifests in the duodenum as celiac like-diese ase. CVID enteropathy patients can present with severe histopathology in form of villous atrophy (CVID VA) or without VA (CVID noVA). RNAseq data from CVID VA and CVID noVA derived duodenal tissues were compared to each other and to healthy controls.
Project description:Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in HLA-DQ2 and/or -DQ8 positive individuals. The hallmarks of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a small subset of individuals with elevated serum tissue transglutaminase antibody (TTG) concentrations but unremarkable duodenal mucosa at initial endoscopy may progress to CeD over time. We hypothesize that these rare CeD precursor cases can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD, and to study the final cascade into overt lesions in CeD.
Project description:Background: Duodenal adenoma/adenocarcinomas are rare, and the global gene expression changes associated with the initial stages of carcinogenesis of these neoplasms have not been elucidated. Results: To comprehensively analyze genetic markers and pathways specific to early-stage duodenal adenoma/adenocarcinomas, transcriptional profiles of 4 fresh-frozen non-ampullary duodenal adenoma/adenocarcinomas and surrounding duodenal normal mucosa were compared. Key features of gene expression analysis demonstrated a strong correlation between these tumors and colorectal adenomas, as well as the Wnt/β-catenin pathway. These results shed new light on the transcriptional changes that occur during the early stages of duodenal tumorigenesis. All samples were obtained prior to treatment in order to minimize effects of cauterization, and immediately fresh-frozen.
Project description:In small animals, diarrhoea is a regular presentation, the aetiology of which can be varied, from an isolated self-limiting event to more serious episodes requiring symptomatic and supportive treatment. Chronic diarrhoea, defined as diarrhoea lasting longer than 3 weeks, is a relatively common problem often prompting referral for more detailed investigation. Although the potential cause of chronic diarrhoea includes chronic intestinal parasitism and alimentary neoplasia (specifically lymphoma), the majority of these dogs will be diagnosed with idiopathic canine chronic enteropathy (CCE), previously referred to as idiopathic inflammatory bowel disease (IBD). Of those cases diagnosed with CCE, further subdivision based on response to treatment trials leads to a final diagnosis of antibiotic responsive diarrhoea (ARD), food responsive diarrhoea (FRD) or idiopathic inflammatory bowl disease (IBD). The aim of this study was to compare the proteomes of faeces of dogs with chronic enteropathies and a population of healthy dogs, and furthermore to identifying proteins that might be useful in distinguishing FRD from ARD from IBD.