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Advances in genomics and a surge in gastrointestinal diseases\n                    <jats:sup>1,2<\/jats:sup>\n                    has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease\n                    <jats:sup>3<\/jats:sup>\n                    . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn\u2019s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner\u2019s glands. Although previously linked to mucosal healing\n                    <jats:sup>4<\/jats:sup>\n                    , we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.\n                  <\/jats:p>","DOI":"10.1038\/s41586-024-07571-1","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T11:04:58Z","timestamp":1732100698000},"page":"699-707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Single-cell integration reveals metaplasia in inflammatory gut diseases"],"prefix":"10.1038","volume":"635","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1690-9027","authenticated-orcid":false,"given":"Amanda J.","family":"Oliver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-038X","authenticated-orcid":false,"given":"Ni","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-9047","authenticated-orcid":false,"given":"Raquel","family":"Bartolome-Casado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5337-9729","authenticated-orcid":false,"given":"Ruoyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Koplev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hogne R.","family":"Nilsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelyn","family":"Moy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-606X","authenticated-orcid":false,"given":"Batuhan","family":"Cakir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-9576","authenticated-orcid":false,"given":"Krzysztof","family":"Polanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Gudi\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Mel\u00f3n-Ardanaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinithi","family":"Sumanaweera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Dimitrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4284-5263","authenticated-orcid":false,"given":"Lisa Marie","family":"Milchsack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-2012","authenticated-orcid":false,"given":"Michael E. 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Oliver was incomplete and has now been amended to \u201cA.J.O. was supported by the European Respiratory Society and the European Union\u2019s H2020 research and innovation program under Marie Sklodowska-Curie grant agreement number 847462\u201d in the HTML and PDF versions of the article.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, a co-founder and equity holder of TransitionBio and EnsoCell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. R.E. is an equity holder in EnsoCell. P.K. has consulted for AstraZeneca, UCB, Biomunex and Infinitopes. N.M.P reports consulting fees from Infinitopes.\u00a0J.S.-R. reports funding from GSK, Pfizer and Sanofi and fees\/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Pfizer, Moderna and Grunenthal. A.S. is the recipient of research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Pfizer, Alimentiv, Boehringer Ingelheim and Agomab and has received consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Agomab, Goodgut and Orikine.\u00a0R.E. and S.A.T are inventors on the patent GB2412853.0 filed in the UK, some components of which are related to this work. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}