{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:57:34Z","timestamp":1791608254663,"version":"4.3.4"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Organoids provide a powerful system to study epithelia <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. Recently, this approach was applied successfully to the biliary tree, a series of ductular tissues responsible for the drainage of bile and pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic bile ducts; EHBDs) or inside the liver (intrahepatic bile ducts; IHBDs). These organoids share many characteristics, including expression of cholangiocyte markers such as keratin (KRT) 19. However, the relationship between these organoids and their tissues of origin, and to each other, is largely unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Organoids were derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs using culture conditions promoting WNT signaling. The resulting IHBD and EHBD organoids expressed stem\/progenitor markers leucine\u2010rich repeat\u2013containing G\u2010protein\u2010coupled receptor 5\/prominin 1 and ductal markers KRT19\/KRT7. However, RNA sequencing revealed that organoids conserve only a limited number of regional\u2010specific markers corresponding to their location of origin. Of particular interest, down\u2010regulation of biliary markers and up\u2010regulation of cell\u2010cycle genes were observed in organoids. IHBD and EHBD organoids diverged in their response to WNT signaling, and only IHBDs were able to express a low level of hepatocyte markers under differentiation conditions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Taken together, our results demonstrate that differences exist not only between extrahepatic biliary organoids and their tissue of origin, but also between IHBD and EHBD organoids. This information may help to understand the tissue specificity of cholangiopathies and also to identify targets for therapeutic development.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31252","type":"journal-article","created":{"date-parts":[[2020,3,29]],"date-time":"2020-03-29T04:31:30Z","timestamp":1585456290000},"page":"247-267","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":109,"title":["Regional Differences in Human Biliary Tissues and Corresponding In Vitro\u2013Derived Organoids"],"prefix":"10.1097","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-6921","authenticated-orcid":false,"given":"Casey A.","family":"Rimland","sequence":"first","affiliation":[{"name":"Wellcome\u2013Medical Research Council Cambridge Stem Cell Institute,University of Cambridge,Cambridge,United Kingdom"},{"name":"Immunopathogenesis Section,Laboratory of Parasitic 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