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Cited by 1,394

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

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Smillie, Christopher S., Biton, Moshe, Ordovas-Montanes, Jose, Sullivan, Keri M., Burgin, Grace, Graham, Daniel B., Herbst, Rebecca H., Rogel, Noga, Slyper, Michal, Waldman, Julia, Sud, Malika, Andrews, Elizabeth, Velonias, Gabriella, Haber, Adam L., Jagadeesh, Karthik, Vickovic, Sanja, Yao, Junmei, Stevens, Christine, Dionne, Danielle, Nguyen, Lan T., Villani, Alexandra-Chloé, Hofree, Matan, Creasey, Elizabeth A., Huang, Hailiang, Rozenblatt-Rosen, Orit, Garber, John J., Khalili, Hamed, Desch, A. Nicole, Daly, Mark J., Ananthakrishnan, Ashwin N., Shalek, Alex K., Xavier, Ramnik J., Regev, Aviv·2019·Cell
DOI 10.1016/j.cell.2019.06.029
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Abstract

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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Metadata

Authors
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., Sud, M., Andrews, E., Velonias, G., Haber, A. L., Jagadeesh, K., Vickovic, S., Yao, J., Stevens, C., Dionne, D., Nguyen, L. T., Villani, A.-C., Hofree, M., Creasey, E. A., Huang, H., Rozenblatt-Rosen, O., Garber, J. J., Khalili, H., Desch, A. N., Daly, M. J., Ananthakrishnan, A. N., Shalek, A. K., Xavier, R. J., & Regev, A.
Venue
Cell
Publisher
Elsevier BV
Published
2019-07
Volume
178
Issue
3
Pages
714-730.e22
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2019.06.029
OpenAlex
W2963622568
Cited by
1,394
References
30
FWCI
73.81
Type
journal article
Language
en
Open access
bronze
Licence
Funders
  • National Institutes of Health
  • Leona M. and Harry B. Helmsley Charitable Trust
  • Klarman Cell Observatory, Broad Institute
  • Howard Hughes Medical Institute

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CoChat. (2026). Citation check: Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. https://app.cochat.ai/papers/10.1016/j.cell.2019.06.029
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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., Sud, M., Andrews, E., Velonias, G., Haber, A. L., Jagadeesh, K., Vickovic, S., Yao, J., Stevens, C., Dionne, D., . . . Regev, A. (2019). Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell. https://doi.org/10.1016/j.cell.2019.06.029

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