Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Christopher S. Smillie, Moshe Biton, Jose Ordovas-Montanes, Keri M. Sullivan, Grace Burgin, Daniel B. Graham, Rebecca H. Herbst, Noga Rogel, Michal Slyper, Julia Waldman, Malika Sud, Elizabeth Andrews, Gabriella Velonias, Adam L. Haber, Karthik Jagadeesh, Sanja Vickovic, Junmei Yao, Christine Stevens, Danielle Dionne, Lan T. Nguyen, Alexandra-Chloé Villani, Matan Hofree, Elizabeth A. Creasey, Hailiang Huang, Orit Rozenblatt-Rosen, John J. Garber, Hamed Khalili, A. Nicole Desch, Mark J. Daly, Ashwin N. Ananthakrishnan, Alex K. Shalek, Ramnik J. Xavier, Aviv Regev

Abstract

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.

Datasets

1. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis
Metadata
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Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

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Source data

https://cellxgene.cziscience.com/collections/33d19f34-87f5-455b-8ca5-9023a2e5453d

Alias names

SCP259, PMID31348891, PMC6662628

Cite this study

Smillie, C.S., Biton, M., Ordovas-Montanes, J., Sullivan, K.M., Burgin, G., Graham, D.B., Herbst, R.H., Rogel, N., Slyper, M., Waldman, J. and Sud, M., 2019. Intra-and inter-cellular rewiring of the human colon during ulcerative colitis. Cell, 178(3), pp.714-730. https://doi.org/10.1016/j.cell.2019.06.029