GSE121380
Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways
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. Overall design: Single cell suspensions of colonic biopsies from eight patients were stained with antibodies and sorted by FACS. Single cell 5' gene expression libraries were prepared for CD45+CD3+CD19- (HB1), CD45+CD3-CD19+ (HB2), CD45+CD3-CD19- (HB3-1) and CD45- (HB4) cells obtained from pooled cells of 4 patients. Single cell 5' gene expression library was prepared for CD45+CD3-CD19- (HB3-2) cells from pooled cells of 2 patients. Single cell 3' gene expression libraries were prepared for CD45+ (S279 and S280) cells obtained from 2 patients respectively. All libraries were constructed according to the 10X Chromium instructions and sequenced on Illumina Hiseq X Ten instrument.