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Cellular and inter-cellular rewiring of the human colon during ulcerative colitis
Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stroma...
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Published in: | Cell 2019-07, Vol.178 (3), p.714-730.e22 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including
BEST4
+
enterocytes, microfold-like cells, and
IL13RA2
+
IL11
+
inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express
CD8
and
IL-17
expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and co-regulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways. |
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ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/j.cell.2019.06.029 |