{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T01:39:15Z","timestamp":1781055555532,"version":"3.54.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["101734\/Z\/13\/Z"],"award-info":[{"award-number":["101734\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["212240\/Z\/18\/Z"],"award-info":[{"award-number":["212240\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health Research Oxford Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>To examine immune-epithelial interactions and their impact on epithelial transformation in primary sclerosing cholangitis\u2013associated ulcerative colitis (PSC-UC) using patient-derived colonic epithelial organoid cultures (EpOCs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The EpOCs were originated from colonic biopsies from patients with PSC-UC (n = 12), patients with UC (n = 14), and control patients (n = 10) and stimulated with cytokines previously associated with intestinal inflammation (interferon (IFN) \u03b3 and interleukin (IL)-22). Markers of cytokine downstream pathways, stemness, and pluripotency were analyzed by real-time quantitative polymerase chain reaction and immunofluorescence. The OLFM4 expression in situ was assessed by RNAscope and immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A distinct expression of stem cell\u2013associated genes was observed in EpOCs derived from patients with PSC-UC, with lower expression of the classical stem-cell marker LGR5 and overexpression of OLFM4, previously associated with pluripotency and early stages of neoplastic transformation in the gastrointestinal and biliary tracts. High levels of OLFM4 were also found ex vivo in colonic biopsies from patients with PSC-UC. In addition, IFN\u03b3 stimulation resulted in the downregulation of LGR5 in EpOCs, whereas higher expression of OLFM4 was observed after IL-22 stimulation. Interestingly, expression of the IL-22 receptor, IL22RA1, was induced by IFN\u03b3, suggesting that a complex interplay between these cytokines may contribute to carcinogenesis in PSC-UC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Higher expression of OLFM4, a cancer stemness gene induced by IL-22, is present in PSC-UC, suggesting that IL-22 responses may result in alterations of the intestinal stem-cell niche in these patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izab025","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T20:01:24Z","timestamp":1613160084000},"page":"1316-1327","source":"Crossref","is-referenced-by-count":20,"title":["Overexpression of Cancer-Associated Stem Cell Gene <i>OLFM4<\/i> in the Colonic Epithelium of Patients With Primary Sclerosing Cholangitis"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-3767","authenticated-orcid":false,"given":"Mastura","family":"Neyazi","sequence":"first","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Services Foundation Trust, John Radcliffe Hospital, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sraddha S","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Services Foundation Trust, John Radcliffe Hospital, University of Oxford , Oxford, 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Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Travis","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Services Foundation Trust, John Radcliffe Hospital, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina V","family":"Arancibia-C\u00e1rcamo","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Services Foundation Trust, John Radcliffe Hospital, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Powrie","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Geremia","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Services Foundation Trust, John Radcliffe Hospital, University of Oxford , Oxford, 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