{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:11:03Z","timestamp":1793862663823,"version":"4.6.1"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["G-1903-03793"],"award-info":[{"award-number":["G-1903-03793"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-51580-7","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T04:52:02Z","timestamp":1724388722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn\u2019s disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Jia","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-5819","authenticated-orcid":false,"given":"Alan J.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline V.","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Chiron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol A.","family":"Ramirez-Solano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6450-9475","authenticated-orcid":false,"given":"Naila","family":"Tasneem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsimran","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Revetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2799-7587","authenticated-orcid":false,"given":"Paige N.","family":"Vega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunxing","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina N.","family":"Tyree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry W.","family":"Raber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N.","family":"Conner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Pilat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-0319","authenticated-orcid":false,"given":"Justin","family":"Jacobse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara M.","family":"McNamara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-1365","authenticated-orcid":false,"given":"Margaret M.","family":"Allaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella A.","family":"Raffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-539X","authenticated-orcid":false,"given":"Alain P.","family":"Gobert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Asim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-2357","authenticated-orcid":false,"given":"Jeremy A.","family":"Goettel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash A.","family":"Choksi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn B.","family":"Beaulieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Dalal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara N.","family":"Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baldeep S.","family":"Pabla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-8065","authenticated-orcid":false,"given":"Yuankai","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5733-2127","authenticated-orcid":false,"given":"Bennett A.","family":"Landman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Roland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Scoville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Kay","family":"Washington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shyr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-1830","authenticated-orcid":false,"given":"Keith T.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-9806","authenticated-orcid":false,"given":"Lori A.","family":"Coburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8438-0319","authenticated-orcid":false,"given":"Ken S.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8892-7078","authenticated-orcid":false,"given":"Qi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"51580_CR1","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","volume":"28","author":"A Kaser","year":"2010","unstructured":"Kaser, A., Zeissig, S. & Blumberg, R. S. Inflammatory bowel disease. Annu. Rev. Immunol. 28, 573\u2013621 (2010).","journal-title":"Annu. Rev. Immunol."},{"key":"51580_CR2","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","volume":"389","author":"J Torres","year":"2017","unstructured":"Torres, J., Mehandru, S., Colombel, J. F. & Peyrin-Biroulet, L. Crohn\u2019s disease. Lancet 389, 1741\u20131755 (2017).","journal-title":"Lancet"},{"key":"51580_CR3","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1016\/S0140-6736(00)05091-1","volume":"357","author":"DA Van Heel","year":"2001","unstructured":"Van Heel, D. A., McGovern, D. P. & Jewell, D. P. Crohn\u2019s disease: genetic susceptibility, bacteria, and innate immunity. Lancet 357, 1902\u20131904 (2001).","journal-title":"Lancet"},{"key":"51580_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-13222-0","volume":"12","author":"AZ Yang","year":"2022","unstructured":"Yang, A. Z. & Jostins-Dean, L. Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort. Sci. Rep. 12, 10890 (2022).","journal-title":"Sci. Rep."},{"key":"51580_CR5","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/nature11582","volume":"491","author":"L Jostins","year":"2012","unstructured":"Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119\u2013124 (2012).","journal-title":"Nature"},{"key":"51580_CR6","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/ng.3359","volume":"47","author":"JZ Liu","year":"2015","unstructured":"Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47, 979\u2013986 (2015).","journal-title":"Nat. Genet."},{"key":"51580_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04365-8","volume":"9","author":"Y Momozawa","year":"2018","unstructured":"Momozawa, Y. et al. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes. Nat. Commun. 9, 2427 (2018).","journal-title":"Nat. Commun."},{"key":"51580_CR8","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/ng.3760","volume":"49","author":"KM de Lange","year":"2017","unstructured":"de Lange, K. M. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat. Genet. 49, 256\u2013261 (2017).","journal-title":"Nat. Genet."},{"key":"51580_CR9","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1016\/j.cell.2018.08.063","volume":"175","author":"AE Moor","year":"2018","unstructured":"Moor, A. E. et al. Spatial reconstruction of single enterocytes uncovers broad zonation along the intestinal villus axis. Cell 175, 1156\u20131167.e1115 (2018).","journal-title":"Cell"},{"key":"51580_CR10","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.cell.2020.12.016","volume":"184","author":"D Fawkner-Corbett","year":"2021","unstructured":"Fawkner-Corbett, D. et al. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell 184, 810\u2013826 e823 (2021).","journal-title":"Cell"},{"key":"51580_CR11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nature24489","volume":"551","author":"AL Haber","year":"2017","unstructured":"Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333\u2013339 (2017).","journal-title":"Nature"},{"key":"51580_CR12","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41586-021-03852-1","volume":"597","author":"R Elmentaite","year":"2021","unstructured":"Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250\u2013255 (2021).","journal-title":"Nature"},{"key":"51580_CR13","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1016\/j.jcmgh.2022.02.007","volume":"13","author":"J Burclaff","year":"2022","unstructured":"Burclaff, J. et al. A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics. Cell Mol. Gastroenterol. Hepatol. 13, 1554\u20131589 (2022).","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"51580_CR14","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41586-019-0992-y","volume":"567","author":"K Parikh","year":"2019","unstructured":"Parikh, K. et al. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature 567, 49\u201355 (2019).","journal-title":"Nature"},{"key":"51580_CR15","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1038\/s41591-021-01520-5","volume":"27","author":"M Friedrich","year":"2021","unstructured":"Friedrich, M. et al. IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nat. Med. 27, 1970\u20131981 (2021).","journal-title":"Nat. Med."},{"key":"51580_CR16","doi-asserted-by":"publisher","unstructured":"Bomidi, C., Robertson, M., Coarfa, C., Estes, M. K. & Blutt, S. E. Single-cell sequencing of rotavirus-infected intestinal epithelium reveals cell-type specific epithelial repair and tuft cell infection. Proc. Natl Acad. Sci. USA, https:\/\/doi.org\/10.1073\/pnas.2112814118 (2021).","DOI":"10.1073\/pnas.2112814118"},{"key":"51580_CR17","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1016\/j.jcmgh.2022.02.005","volume":"13","author":"M Kanke","year":"2022","unstructured":"Kanke, M. et al. Single-cell analysis reveals unexpected cellular changes and transposon expression signatures in the colonic epithelium of treatment-naive adult Crohn\u2019s disease patients. Cell Mol. Gastroenterol. Hepatol. 13, 1717\u20131740 (2022).","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"51580_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22164-6","volume":"12","author":"N Jaeger","year":"2021","unstructured":"Jaeger, N. et al. Single-cell analyses of Crohn\u2019s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions. Nat. Commun. 12, 1921 (2021).","journal-title":"Nat. Commun."},{"key":"51580_CR19","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.cell.2019.08.008","volume":"178","author":"JC Martin","year":"2019","unstructured":"Martin, J. C. et al. Single-cell analysis of Crohn\u2019s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy. Cell 178, 1493\u20131508.e1420 (2019).","journal-title":"Cell"},{"key":"51580_CR20","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1053\/j.gastro.2020.04.074","volume":"159","author":"V Mitsialis","year":"2020","unstructured":"Mitsialis, V. et al. Single-cell analyses of colon and blood reveal distinct immune cell signatures of ulcerative colitis and Crohn\u2019s disease. Gastroenterology 159, 591\u2013608.e510 (2020).","journal-title":"Gastroenterology"},{"key":"51580_CR21","doi-asserted-by":"publisher","unstructured":"Boland, B. S. et al. Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses. Sci. Immunol. https:\/\/doi.org\/10.1126\/sciimmunol.abb4432 (2020).","DOI":"10.1126\/sciimmunol.abb4432"},{"key":"51580_CR22","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.cell.2019.06.029","volume":"178","author":"CS Smillie","year":"2019","unstructured":"Smillie, C. S. et al. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell 178, 714\u2013730 e722 (2019).","journal-title":"Cell"},{"key":"51580_CR23","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jcmgh.2021.01.020","volume":"12","author":"G Li","year":"2021","unstructured":"Li, G. et al. Identification of novel population-specific cell subsets in chinese ulcerative colitis patients using single-cell RNA sequencing. Cell Mol. Gastroenterol. Hepatol. 12, 99\u2013117 (2021).","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"51580_CR24","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.devcel.2020.11.010","volume":"55","author":"R Elmentaite","year":"2020","unstructured":"Elmentaite, R. et al. Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn\u2019s disease. Dev. Cell 55, 771\u2013783.e775 (2020).","journal-title":"Dev. Cell"},{"key":"51580_CR25","doi-asserted-by":"publisher","unstructured":"Rosati, E. et al. A novel unconventional T cell population enriched in Crohn\u2019s disease. Gut, https:\/\/doi.org\/10.1136\/gutjnl-2021-325373 (2022).","DOI":"10.1136\/gutjnl-2021-325373"},{"key":"51580_CR26","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/s41590-021-01110-0","volume":"23","author":"L Zhou","year":"2022","unstructured":"Zhou, L. et al. Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation. Nat. Immunol. 23, 251\u2013261 (2022).","journal-title":"Nat. Immunol."},{"key":"51580_CR27","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1053\/j.gastro.2018.10.046","volume":"156","author":"WT Uniken Venema","year":"2019","unstructured":"Uniken Venema, W. T. et al. Single-cell RNA sequencing of blood and ileal T cells from patients with Crohn\u2019s disease reveals tissue-specific characteristics and drug targets. Gastroenterology 156, 812\u2013815.e822 (2019).","journal-title":"Gastroenterology"},{"key":"51580_CR28","doi-asserted-by":"publisher","unstructured":"Wang, Y. et al. Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20191130 (2020).","DOI":"10.1084\/jem.20191130"},{"key":"51580_CR29","doi-asserted-by":"publisher","first-page":"e2006687","DOI":"10.1371\/journal.pbio.2006687","volume":"16","author":"Q Liu","year":"2018","unstructured":"Liu, Q. et al. Quantitative assessment of cell population diversity in single-cell landscapes. PLoS Biol. 16, e2006687 (2018).","journal-title":"PLoS Biol."},{"key":"51580_CR30","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nm.4307","volume":"23","author":"NR West","year":"2017","unstructured":"West, N. R. et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat. Med. 23, 579\u2013589 (2017).","journal-title":"Nat. Med."},{"key":"51580_CR31","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.4049\/jimmunol.2100220","volume":"207","author":"ME Keir","year":"2021","unstructured":"Keir, M. E. et al. Regulation and role of alphaE integrin and gut homing integrins in migration and retention of intestinal lymphocytes during inflammatory Bowel disease. J. Immunol. 207, 2245\u20132254 (2021).","journal-title":"J. Immunol."},{"key":"51580_CR32","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1097\/MIB.0000000000001246","volume":"23","author":"M Vancamelbeke","year":"2017","unstructured":"Vancamelbeke, M. et al. Genetic and transcriptomic bases of intestinal epithelial barrier dysfunction in inflammatory Bowel disease. Inflamm. Bowel Dis. 23, 1718\u20131729 (2017).","journal-title":"Inflamm. Bowel Dis."},{"key":"51580_CR33","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1093\/ecco-jcc\/jjac021","volume":"16","author":"M Ngollo","year":"2022","unstructured":"Ngollo, M. et al. Identification of gene expression profiles associated with an increased risk of post-operative recurrence in Crohn\u2019s disease. J. Crohns Colitis 16, 1269\u20131280 (2022).","journal-title":"J. Crohns Colitis"},{"key":"51580_CR34","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1053\/j.gastro.2018.05.028","volume":"155","author":"KL VanDussen","year":"2018","unstructured":"VanDussen, K. L. et al. Abnormal small intestinal epithelial microvilli in patients with Crohn\u2019s disease. Gastroenterology 155, 815\u2013828 (2018).","journal-title":"Gastroenterology"},{"key":"51580_CR35","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1002\/ibd.21263","volume":"16","author":"CL Noble","year":"2010","unstructured":"Noble, C. L. et al. Characterization of intestinal gene expression profiles in Crohn\u2019s disease by genome-wide microarray analysis. Inflamm. Bowel Dis. 16, 1717\u20131728 (2010).","journal-title":"Inflamm. Bowel Dis."},{"key":"51580_CR36","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1097\/MIB.0000000000000478","volume":"21","author":"BC Peck","year":"2015","unstructured":"Peck, B. C. et al. MicroRNAs classify different disease behavior phenotypes of Crohn\u2019s disease and may have prognostic utility. Inflamm. Bowel Dis. 21, 2178\u20132187 (2015).","journal-title":"Inflamm. Bowel Dis."},{"key":"51580_CR37","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S1097-2765(02)00708-6","volume":"10","author":"DH Goetz","year":"2002","unstructured":"Goetz, D. H. et al. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell 10, 1033\u20131043 (2002).","journal-title":"Mol. Cell"},{"key":"51580_CR38","first-page":"2327","volume":"21","author":"J Stallhofer","year":"2015","unstructured":"Stallhofer, J. et al. Lipocalin-2 is a disease activity marker in inflammatory Bowel disease regulated by IL-17A, IL-22, and TNF-alpha and modulated by IL23R genotype status. Inflamm. Bowel Dis. 21, 2327\u20132340 (2015).","journal-title":"Inflamm. Bowel Dis."},{"key":"51580_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39232-z","volume":"9","author":"EA Scoville","year":"2019","unstructured":"Scoville, E. A. et al. Serum polyunsaturated fatty acids correlate with serum cytokines and clinical disease activity in Crohn\u2019s disease. Sci. Rep. 9, 2882 (2019).","journal-title":"Sci. Rep."},{"key":"51580_CR40","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1093\/ibd\/izad050","volume":"29","author":"L Deng","year":"2023","unstructured":"Deng, L. et al. Identification of lipocalin 2 as a potential ferroptosis-related gene in ulcerative colitis. Inflamm. Bowel Dis. 29, 1446\u20131457 (2023).","journal-title":"Inflamm. Bowel Dis."},{"key":"51580_CR41","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/j.1462-5822.2010.01559.x","volume":"13","author":"H Muhl","year":"2011","unstructured":"Muhl, H., Bachmann, M. & Pfeilschifter, J. Inducible NO synthase and antibacterial host defence in times of Th17\/Th22\/T22 immunity. Cell Microbiol. 13, 340\u2013348 (2011).","journal-title":"Cell Microbiol."},{"key":"51580_CR42","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1097\/MIB.0000000000000790","volume":"22","author":"LA Coburn","year":"2016","unstructured":"Coburn, L. A. et al. L-Arginine availability and metabolism is altered in ulcerative colitis. Inflamm. Bowel Dis. 22, 1847\u20131858 (2016).","journal-title":"Inflamm. Bowel Dis."},{"key":"51580_CR43","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1136\/gut.36.5.718","volume":"36","author":"D Rachmilewitz","year":"1995","unstructured":"Rachmilewitz, D. et al. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn\u2019s disease. Gut 36, 718\u2013723 (1995).","journal-title":"Gut"},{"key":"51580_CR44","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1023\/A:1018849405922","volume":"42","author":"H Kimura","year":"1997","unstructured":"Kimura, H. et al. Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn\u2019s disease. Dig. Dis. Sci. 42, 1047\u20131054 (1997).","journal-title":"Dig. Dis. Sci."},{"key":"51580_CR45","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1136\/jcp.51.10.750","volume":"51","author":"N Leonard","year":"1998","unstructured":"Leonard, N., Bishop, A. E., Polak, J. M. & Talbot, I. C. Expression of nitric oxide synthase in inflammatory bowel disease is not affected by corticosteroid treatment. J. Clin. Pathol. 51, 750\u2013753 (1998).","journal-title":"J. Clin. Pathol."},{"key":"51580_CR46","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/S0016-5085(96)70055-0","volume":"111","author":"II Singer","year":"1996","unstructured":"Singer, I. I. et al. Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology 111, 871\u2013885 (1996).","journal-title":"Gastroenterology"},{"key":"51580_CR47","doi-asserted-by":"publisher","first-page":"G137","DOI":"10.1152\/ajpgi.00309.2003","volume":"286","author":"PL Beck","year":"2004","unstructured":"Beck, P. L. et al. Paradoxical roles of different nitric oxide synthase isoforms in colonic injury. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G137\u2013147 (2004).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"51580_CR48","doi-asserted-by":"publisher","first-page":"G865","DOI":"10.1152\/ajpgi.00187.2004","volume":"287","author":"BA Vallance","year":"2004","unstructured":"Vallance, B. A. et al. Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G865\u2013874, (2004).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"51580_CR49","doi-asserted-by":"publisher","first-page":"e33546","DOI":"10.1371\/journal.pone.0033546","volume":"7","author":"LA Coburn","year":"2012","unstructured":"Coburn, L. A. et al. L-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis. PLoS ONE 7, e33546 (2012).","journal-title":"PLoS ONE"},{"key":"51580_CR50","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s12275-018-7545-1","volume":"56","author":"D Sarr","year":"2018","unstructured":"Sarr, D., Toth, E., Gingerich, A. & Rada, B. Antimicrobial actions of dual oxidases and lactoperoxidase. J. Microbiol. 56, 373\u2013386 (2018).","journal-title":"J. Microbiol."},{"key":"51580_CR51","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1089\/ars.2020.8018","volume":"33","author":"PM Dang","year":"2020","unstructured":"Dang, P. M., Rolas, L. & El-Benna, J. The dual role of reactive oxygen species-generating nicotinamide adenine dinucleotide phosphate oxidases in gastrointestinal inflammation and therapeutic perspectives. Antioxid. Redox Signal 33, 354\u2013373 (2020).","journal-title":"Antioxid. Redox Signal"},{"key":"51580_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.109015","volume":"238","author":"R Kyodo","year":"2022","unstructured":"Kyodo, R. et al. Novel biallelic mutations in the DUOX2 gene underlying very early-onset inflammatory bowel disease: a case report. Clin. Immunol. 238, 109015 (2022).","journal-title":"Clin. Immunol."},{"key":"51580_CR53","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1053\/j.gastro.2020.10.031","volume":"160","author":"JF Burgueno","year":"2021","unstructured":"Burgueno, J. F. et al. Epithelial TLR4 signaling activates DUOX2 to induce microbiota-driven tumorigenesis. Gastroenterology 160, 797\u2013808.e796 (2021).","journal-title":"Gastroenterology"},{"key":"51580_CR54","doi-asserted-by":"publisher","first-page":"3522","DOI":"10.1242\/jcs.050690","volume":"122","author":"S Lipinski","year":"2009","unstructured":"Lipinski, S. et al. DUOX2-derived reactive oxygen species are effectors of NOD2-mediated antibacterial responses. J. Cell Sci. 122, 3522\u20133530 (2009).","journal-title":"J. Cell Sci."},{"key":"51580_CR55","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","volume":"560","author":"G La Manno","year":"2018","unstructured":"La Manno, G. et al. RNA velocity of single cells. Nature 560, 494\u2013498 (2018).","journal-title":"Nature"},{"key":"51580_CR56","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1663-x","volume":"20","author":"FA Wolf","year":"2019","unstructured":"Wolf, F. A. et al. PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells. Genome Biol. 20, 59 (2019).","journal-title":"Genome Biol."},{"key":"51580_CR57","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1126\/science.aax0249","volume":"367","author":"GS Gulati","year":"2020","unstructured":"Gulati, G. S. et al. Single-cell transcriptional diversity is a hallmark of developmental potential. Science 367, 405\u2013411 (2020).","journal-title":"Science"},{"key":"51580_CR58","doi-asserted-by":"publisher","first-page":"e7984","DOI":"10.1371\/journal.pone.0007984","volume":"4","author":"I Arijs","year":"2009","unstructured":"Arijs, I. et al. Mucosal gene expression of antimicrobial peptides in inflammatory bowel disease before and after first infliximab treatment. PLoS ONE 4, e7984 (2009).","journal-title":"PLoS ONE"},{"key":"51580_CR59","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","volume":"12","author":"AM Newman","year":"2015","unstructured":"Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453\u2013457 (2015).","journal-title":"Nat. Methods"},{"key":"51580_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin, S. et al. Inference and analysis of cell-cell communication using CellChat. Nat. Commun. 12, 1088 (2021).","journal-title":"Nat. Commun."},{"key":"51580_CR61","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1101\/gr.276851.122","volume":"32","author":"Q Liu","year":"2022","unstructured":"Liu, Q., Hsu, C. Y. & Shyr, Y. Scalable and model-free detection of spatial patterns and colocalization. Genome Res. 32, 1736\u20131745 (2022).","journal-title":"Genome Res."},{"key":"51580_CR62","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41587-021-00830-w","volume":"40","author":"DM Cable","year":"2022","unstructured":"Cable, D. M. et al. Robust decomposition of cell type mixtures in spatial transcriptomics. Nat. Biotechnol. 40, 517\u2013526 (2022).","journal-title":"Nat. Biotechnol."},{"key":"51580_CR63","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.1093\/bioinformatics\/btu326","volume":"30","author":"K Slowikowski","year":"2014","unstructured":"Slowikowski, K., Hu, X. & Raychaudhuri, S. SNPsea: an algorithm to identify cell types, tissues and pathways affected by risk loci. Bioinformatics 30, 2496\u20132497 (2014).","journal-title":"Bioinformatics"},{"key":"51580_CR64","doi-asserted-by":"publisher","first-page":"e46","DOI":"10.1038\/ctg.2013.17","volume":"5","author":"SS Dhillon","year":"2014","unstructured":"Dhillon, S. S. et al. Higher activity of the inducible nitric oxide synthase contributes to very early onset inflammatory bowel disease. Clin. Transl. Gastroenterol. 5, e46 (2014).","journal-title":"Clin. Transl. Gastroenterol."},{"key":"51580_CR65","doi-asserted-by":"publisher","unstructured":"Grasberger, H. et al. DUOX2 variants associate with preclinical disturbances in microbiota-immune homeostasis and increased inflammatory bowel disease risk. J. Clin. Invest. https:\/\/doi.org\/10.1172\/JCI141676 (2021).","DOI":"10.1172\/JCI141676"},{"key":"51580_CR66","doi-asserted-by":"publisher","unstructured":"Kluber, P. et al. Depletion of lipocalin 2 (LCN2) in mice leads to dysbiosis and persistent colonization with segmented filamentous bacteria. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms222313156 (2021).","DOI":"10.3390\/ijms222313156"},{"key":"51580_CR67","doi-asserted-by":"publisher","first-page":"e82300","DOI":"10.1371\/journal.pone.0082300","volume":"8","author":"LA Coburn","year":"2013","unstructured":"Coburn, L. A. et al. High-throughput multi-analyte Luminex profiling implicates eotaxin-1 in ulcerative colitis. PLoS ONE 8, e82300 (2013).","journal-title":"PLoS ONE"},{"key":"51580_CR68","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","volume":"42","author":"PA Harris","year":"2009","unstructured":"Harris, P. A. et al. Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inf. 42, 377\u2013381 (2009).","journal-title":"J. Biomed. Inf."},{"key":"51580_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208","volume":"95","author":"PA Harris","year":"2019","unstructured":"Harris, P. A. et al. The REDCap consortium: building an international community of software platform partners. J. Biomed. Inf. 95, 103208 (2019).","journal-title":"J. Biomed. Inf."},{"key":"51580_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2021.103871","volume":"121","author":"AC Cheng","year":"2021","unstructured":"Cheng, A. C. et al. REDCap on FHIR: clinical data interoperability services. J. Biomed. Inf. 121, 103871 (2021).","journal-title":"J. Biomed. Inf."},{"key":"51580_CR71","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1017\/cts.2020.30","volume":"4","author":"CE Lawrence","year":"2020","unstructured":"Lawrence, C. E. et al. A REDCap-based model for electronic consent (eConsent): moving toward a more personalized consent. J. Clin. Transl. Sci. 4, 345\u2013353 (2020).","journal-title":"J. Clin. Transl. Sci."},{"key":"51580_CR72","doi-asserted-by":"publisher","first-page":"6262","DOI":"10.1016\/j.cell.2021.11.031","volume":"184","author":"B Chen","year":"2021","unstructured":"Chen, B. et al. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps. Cell 184, 6262\u20136280.e6226 (2021).","journal-title":"Cell"},{"key":"51580_CR73","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101570","volume":"3","author":"AJ Simmons","year":"2022","unstructured":"Simmons, A. J. & Lau, K. S. Dissociation and inDrops microfluidic encapsulation of human gut tissues for single-cell atlasing studies. STAR Protoc. 3, 101570 (2022).","journal-title":"STAR Protoc."},{"key":"51580_CR74","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1053\/j.gastro.2020.08.029","volume":"159","author":"A Banerjee","year":"2020","unstructured":"Banerjee, A. et al. Succinate produced by intestinal microbes promotes specification of tuft cells to suppress ileal inflammation. Gastroenterology 159, 2101\u20132115.e2105 (2020).","journal-title":"Gastroenterology"},{"key":"51580_CR75","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.cell.2015.04.044","volume":"161","author":"AM Klein","year":"2015","unstructured":"Klein, A. M. et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187\u20131201 (2015).","journal-title":"Cell"},{"key":"51580_CR76","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-06843-0","volume":"21","author":"AN Southard-Smith","year":"2020","unstructured":"Southard-Smith, A. N. et al. Dual indexed library design enables compatibility of in-Drop single-cell RNA-sequencing with exAMP chemistry sequencing platforms. BMC Genomics 21, 456 (2020).","journal-title":"BMC Genomics"},{"key":"51580_CR77","doi-asserted-by":"publisher","unstructured":"Choi, H. M. T. et al. Third-generation in situ hybridization chain reaction: multiplexed, quantitative, sensitive, versatile, robust. Development, https:\/\/doi.org\/10.1242\/dev.165753 (2018).","DOI":"10.1242\/dev.165753"},{"key":"51580_CR78","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cels.2017.10.012","volume":"6","author":"CA Herring","year":"2018","unstructured":"Herring, C. A. et al. Unsupervised trajectory analysis of single-cell RNA-seq and imaging data reveals alternative tuft cell origins in the gut. Cell Syst. 6, 37\u201351.e39 (2018).","journal-title":"Cell Syst."},{"key":"51580_CR79","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.878920","volume":"12","author":"PN Vega","year":"2022","unstructured":"Vega, P. N. et al. Cancer-associated fibroblasts and squamous epithelial cells constitute a unique microenvironment in a mouse model of inflammation-induced colon cancer. Front Oncol. 12, 878920 (2022).","journal-title":"Front Oncol."},{"key":"51580_CR80","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/cyto.a.24541","volume":"101","author":"ET McKinley","year":"2022","unstructured":"McKinley, E. T. et al. MIRIAM: a machine and deep learning single-cell segmentation and quantification pipeline for multi-dimensional tissue images. Cytom. A 101, 521\u2013528 (2022).","journal-title":"Cytom. A"},{"key":"51580_CR81","doi-asserted-by":"publisher","first-page":"5620","DOI":"10.1016\/j.cell.2023.11.006","volume":"186","author":"CN Heiser","year":"2023","unstructured":"Heiser, C. N. et al. Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors. Cell 186, 5620\u20135637.e5616 (2023).","journal-title":"Cell"},{"key":"51580_CR82","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1449-6","volume":"19","author":"V Petukhov","year":"2018","unstructured":"Petukhov, V. et al. dropEst: pipeline for accurate estimation of molecular counts in droplet-based single-cell RNA-seq experiments. Genome Biol. 19, 78 (2018).","journal-title":"Genome Biol."},{"key":"51580_CR83","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"51580_CR84","doi-asserted-by":"publisher","first-page":"5306","DOI":"10.1093\/bioinformatics\/btz601","volume":"35","author":"Q Liu","year":"2019","unstructured":"Liu, Q. et al. scRNABatchQC: multi-samples quality control for single cell RNA-seq data. Bioinformatics 35, 5306\u20135308 (2019).","journal-title":"Bioinformatics"},{"key":"51580_CR85","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411\u2013420 (2018).","journal-title":"Nat. Biotechnol."},{"key":"51580_CR86","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902.e1821 (2019).","journal-title":"Cell"},{"key":"51580_CR87","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1093\/nar\/gkab931","volume":"50","author":"J Li","year":"2022","unstructured":"Li, J., Sheng, Q., Shyr, Y. & Liu, Q. scMRMA: single cell multiresolution marker-based annotation. Nucleic Acids Res 50, e7 (2022).","journal-title":"Nucleic Acids Res"},{"key":"51580_CR88","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1053\/j.gastro.2023.05.041","volume":"165","author":"AP Gobert","year":"2023","unstructured":"Gobert, A. P. et al. Hypusination maintains intestinal homeostasis and prevents colitis and carcinogenesis by enhancing aldehyde detoxification. Gastroenterology 165, 656\u2013669 e658 (2023).","journal-title":"Gastroenterology"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-51580-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-51580-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-51580-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T06:43:43Z","timestamp":1724395423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-51580-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":88,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["51580"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-51580-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.09.30.560293","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]},"assertion":[{"value":"28 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7204"}}