Oct 29, 2018

Rewiring of the cellular and inter-cellular landscape of the human colon during ulcerative colitis

BioRxiv : the Preprint Server for Biology
Christopher S. SmillieAviv Regev

Abstract

Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC), but their cell type and pathway specificities are often unknown. Here, we generate an atlas of 115,517 cells from the colon mucosa of seven UC patients and ten healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets. These included a subset of BEST4+ enterocytes, which may sense and respond to pH, and IL13RA2+IL-11+ inflammatory fibroblasts, which we associate with resistance to anti-TNF therapy. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and CD8+IL-17+ T cells expand during disease, and form intercellular interaction hubs that mediate cross-talk between diverse cellular lineages. We identify hundreds of putative autocrine and paracrine cell-cell interactions that may explain the migration, expansion, or inhibition of cell types with disease. Surprisingly, UC risk genes are often cell type specific and co-regulated in relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer putative functions for UC risk genes across all GWAS loci. Our atlas thus provides a framework for interrogating complex human...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Transcription Cofactor Activity
Biochemical Pathway
T-Lymphocyte
Specimen Type - Fibroblasts
Cross-talk
Anti-tumor Necrosis Factor Therapy
Genes
Microfold Cell
Recombinant Interleukin-17

About this Paper

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