{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:16:36Z","timestamp":1792440996967,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Biliary atresia is a severe inflammatory and fibrosing cholangiopathy of neonates of unknown etiology. The onset of cholestasis at birth implies a prenatal onset of liver dysfunction. Our aim was to investigate the mechanisms linked to abnormal cholangiocyte development.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We generated biliary organoids from liver biopsies of infants with biliary atresia and normal and diseased controls. Organoids emerged from biliary atresia livers and controls and grew as lumen\u2010containing spheres with an epithelial lining of cytokeratin\u201019<jats:sup>pos<\/jats:sup>albumin<jats:sup>neg<\/jats:sup>SOX17<jats:sup>neg<\/jats:sup> cholangiocyte\u2010like cells. Spheres had similar gross morphology in all three groups and expressed cholangiocyte\u2010enriched genes. In biliary atresia, cholangiocyte\u2010like cells lacked a basal positioning of the nucleus, expressed fewer developmental and functional markers, and displayed misorientation of cilia. They aberrantly expressed F\u2010actin, \u03b2\u2010catenin, and Ezrin, had low signals for the tight junction protein zonula occludens\u20101 (ZO\u20101), and displayed increased permeability as evidenced by a higher Rhodamine\u2010123 (R123) signal inside organoids after verapamil treatment. Biliary atresia organoids had decreased expression of genes related to EGF signaling and FGF2 signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation (cytokeratin 7 and hepatocyte nuclear factor 1 homeobox B) and functional (somatostatin receptor 2, cystic fibrosis transmembrane conductance regulator [CFTR], aquaporin 1) markers, restored polarity with improved localization of F\u2010actin, \u03b2\u2010catenin and ZO\u20101, increased CFTR function, and decreased uptake of R123.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell\u2010cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32107","type":"journal-article","created":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T11:07:11Z","timestamp":1629025631000},"page":"89-103","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":93,"title":["Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia"],"prefix":"10.1097","volume":"75","author":[{"given":"Surya P.","family":"Amarachintha","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mourya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Ayabe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine,The First Affiliated Hospital of Sun Yat\u2010Sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,The Third Affiliated Hospital of Sun Yat\u2010Sen University, Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unmesha","family":"Thanekar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranavkumar","family":"Shivakumar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9667-7742","authenticated-orcid":false,"given":"Jorge A.","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,Ohio,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12,4]]},"reference":[{"key":"hep32107-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41576-019-0169-4","article-title":"Mechanisms of early placental development in mouse and humans","volume":"21","year":"2020","journal-title":"Nat Rev 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