ABSTRACT: Colonic mucosal microbiota and association of bacterial taxa with the expression of host antimicrobial peptides in pediatric ulcerative colitis
Project description:Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn’s disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.
Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Keywords: Disease state analysis
Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Experiment Overall Design: The series contain eight UC samples with macroscopic signs of inflammation, 13 UC smaples without macroscopic signs of inflammation, five control subjects.
Project description:10x Chromium 5' single cell RNA-Seq and VDJ sequencing of colonic CD8+ T cell cell populations in health and Ulcerative Colitis in human patients.
Project description:Aims: Single-cell transcriptomic analysis of CD8 T cells in colonic tissue in Health and Ulcerative Colitis Results: We demonstrated significant heterogeneity within the CD8 population, defined disease associated populations and traced lineage relationships between different T cell subtypes
Project description:Peripheral blood-derived macrophages were stimulated with viral-like particles isolated from colonic resections from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-IBD controls diagnoses. RNAseq was performed to unbiasedly assess the transcriptional responses to these stimuli and revealed highly divergent macrophage transcriptional programs in response to non-IBD compared to IBD VLP.
Project description:Inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory diseases with increasing worldwide prevalence that show a perplexing heterogeneity in manifestations and response to treatment. We applied single cell RNA sequencing (scRNAseq) a to colonic tissue from a combined healthy, UC and CD cohort.
Project description:The etiology of the inflammatory bowel diseases, including ulcerative colitis, remains incomplete, but recent findings points to the involvement of complex host-microbial interactions. We hypothesized that an analysis of the proteins on the host-microbial interacting surface, the intestinal mucosa, could reveal novel insights into the diseases. Mucosal colonic biopsies were extracted by standard colonscopy from sigmoideum from 10 ulcerative colitis patients from non-inflammed tissue and 10 controls. The biopsies were immediately following extraction snap-frozen for protein analysis and the protein content of the biopsies was characterized by high-throughput quantative gel-free proteomics.
Project description:Using recal mucosal biopsies, collected prior to treatment in new-onset pediatric ulcerative colitis patients, we performed RNAsequencing to generate transcriptomic profiles linked to pathogenesis, severity, and treatment response.
