{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:05:23Z","timestamp":1790096723381,"version":"4.0.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007929","name":"Institute for Translational Medicine and Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007929","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006920","name":"University of Pennsylvania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH P30DK050306"],"award-info":[{"award-number":["NIH P30DK050306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23DK100461"],"award-info":[{"award-number":["K23DK100461"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01DK100485"],"award-info":[{"award-number":["K01DK100485"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DK114463"],"award-info":[{"award-number":["R03DK114463"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK124369"],"award-info":[{"award-number":["R01DK124369"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08DK106444-01"],"award-info":[{"award-number":["K08DK106444-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DK118310"],"award-info":[{"award-number":["R03DK118310"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01DK103953"],"award-info":[{"award-number":["K01DK103953"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK121159"],"award-info":[{"award-number":["R01DK121159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK111843"],"award-info":[{"award-number":["R01DK111843"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI123538"],"award-info":[{"award-number":["1R01AI123538"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for Molecular Studies in Digestive and Liver Diseases"},{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Asociacion Espa\u00f1ola Contra el Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Defining epithelial cell contributions to inflammatory bowel disease (IBD) is essential for the development of much needed therapies for barrier repair. Children with very early onset (VEO)-IBD have more extensive, severe, and refractory disease than older children and adults with IBD and, in some cases, have defective barrier function. We therefore evaluated functional and transcriptomic differences between pediatric IBD (VEO and older onset) and non-IBD epithelium using 3-dimensional, biopsy-derived organoids.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We measured growth efficiency relative to histopathological and clinical parameters in patient enteroid (ileum) and colonoid (colon) lines. We performed RNA-sequencing on patient colonoids and subsequent flow cytometry after multiple passages to evaluate changes that persisted in culture.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Enteroids and colonoids from pediatric patients with IBD exhibited decreased growth associated with histological inflammation compared with non-IBD controls. We observed increased LYZ expression in colonoids from pediatric IBD patients, which has been reported previously in adult patients with IBD. We also observed upregulation of antigen presentation genes HLA-DRB1 and HLA-DRA, which persisted after prolonged passaging in patients with pediatric IBD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We present the first functional evaluation of enteroids and colonoids from patients with VEO-IBD and older onset pediatric IBD, a subset of which exhibits poor growth. Enhanced, persistent epithelial antigen presentation gene expression in patient colonoids supports the notion that epithelial cell-intrinsic differences may contribute to IBD pathogenesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izaa145","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T06:15:07Z","timestamp":1592547307000},"page":"256-267","source":"Crossref","is-referenced-by-count":23,"title":["Colonoids From Patients With Pediatric Inflammatory Bowel Disease Exhibit Decreased Growth Associated With Inflammation Severity and Durable Upregulation of Antigen Presentation Genes"],"prefix":"10.1093","volume":"27","author":[{"given":"Judith R","family":"Kelsen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Dawany","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maire A","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana A","family":"Karakasheva","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Maurer","sequence":"additional","affiliation":[{"name":"Division of Allergy Immunology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selen","family":"Uman","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiah H","family":"Dent","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithika","family":"Behera","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Clinic, Centro de Investigacion Biomedica en Red en Enfermedades Hepaticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona , Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Chatterji","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Shraim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Merz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Medicine, Gastroenterology Division, University of Pennsylvania , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda B","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Giraudo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Behrens","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A","family":"Whelan","sequence":"additional","affiliation":[{"name":"Fels Institute for Cancer Research & Molecular Biology, Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine at Temple University , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Devoto","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, United States"},{"name":"Division of Anatomic Pathology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre A","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health & Science University , Portland, OR, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F","family":"Andres","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, University of Rome Sapienza , Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen E","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Allergy Immunology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9575-2499","authenticated-orcid":false,"given":"Kathryn E","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children\u2019s Hospital of Philadelphia , Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"2022092011213213800_CIT0001","doi-asserted-by":"crossref","first-page":"G1359","DOI":"10.1152\/ajpgi.00493.2011","article-title":"A nomenclature for intestinal in vitro cultures","volume":"302","author":"Stelzner","year":"2012","journal-title":"Am J Physiol Gastrointest Liver 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Crohn\u2019s disease: a truly long-term model to study the molecular basis for inflammatory bowel disease?","volume":"66","author":"Noben","year":"2017","journal-title":"Gut."},{"key":"2022092011213213800_CIT0008","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1074\/jbc.R114.635995","article-title":"Human enteroids\/colonoids and intestinal organoids functionally recapitulate normal intestinal physiology and pathophysiology","volume":"291","author":"Zachos","year":"2016","journal-title":"J Biol Chem."},{"key":"2022092011213213800_CIT0009","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1136\/gutjnl-2012-303333","article-title":"Transcriptional analysis of the intestinal mucosa of patients with ulcerative colitis in remission reveals lasting epithelial cell 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