{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:10:57Z","timestamp":1790845857976,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grant Council Theme-based Research Scheme 2021-22","award":["T12-712\/21-R"],"award-info":[{"award-number":["T12-712\/21-R"]}]},{"name":"Research Grant Council Theme-based Research Scheme 2021-22","award":["17105119"],"award-info":[{"award-number":["17105119"]}]},{"name":"Research Grant Council Theme-based Research Scheme 2021-22","award":["201910159198"],"award-info":[{"award-number":["201910159198"]}]},{"name":"Research Grant Council CERG Grant 2019\/20","award":["T12-712\/21-R"],"award-info":[{"award-number":["T12-712\/21-R"]}]},{"name":"Research Grant Council CERG Grant 2019\/20","award":["17105119"],"award-info":[{"award-number":["17105119"]}]},{"name":"Research Grant Council CERG Grant 2019\/20","award":["201910159198"],"award-info":[{"award-number":["201910159198"]}]},{"name":"Seed Funding for Basic Research, HKU","award":["T12-712\/21-R"],"award-info":[{"award-number":["T12-712\/21-R"]}]},{"name":"Seed Funding for Basic Research, HKU","award":["17105119"],"award-info":[{"award-number":["17105119"]}]},{"name":"Seed Funding for Basic Research, HKU","award":["201910159198"],"award-info":[{"award-number":["201910159198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA disease mechanism in humans, we treated normal human liver organoids with biliatresone and addressed its adverse effects on organoid development, functions and cellular organization. The control organoids (without biliatresone) were well expanded and much bigger than biliatresone-treated organoids. Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids. ZO-1 (a tight junction marker) immunoreactivity was localized at the apical intercellular junctions in control organoids, while it was markedly reduced in biliatresone-treated organoids. Cytoskeleton F-actin was localized at the apical surface of the control organoids, but it was ectopically expressed at the apical and basal sides in biliatresone-treated organoids. Cholangiocytes of control organoids possess primary cilia and elicit cilia mechanosensory function. The number of ciliated cholangiocytes was reduced, and cilia mechanosensory function was hampered in biliatresone-treated organoids. In conclusion, biliatresone induces morphological and developmental changes in human liver organoids resembling those of our previously reported BA organoids, suggesting that environmental toxins could contribute to BA pathogenesis.<\/jats:p>","DOI":"10.3390\/toxins16030144","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T11:05:10Z","timestamp":1710155110000},"page":"144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Environmental Toxin Biliatresone-Induced Biliary Atresia-like Abnormal Cilia and Bile Duct Cell Development of Human Liver Organoids"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-8074","authenticated-orcid":false,"given":"Yue","family":"Hai-Bing","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menon Sudheer","family":"Sivasankaran","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babu Rosana","family":"Ottakandathil","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Zhong-Luan","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Man-Ting","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-5681","authenticated-orcid":false,"given":"Chung (Patrick)","family":"Ho-Yu","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7371-503X","authenticated-orcid":false,"given":"Wong (Kenneth)","family":"Kak-Yuen","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6231-3035","authenticated-orcid":false,"given":"Tam (Paul)","family":"Kwong-Hang","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Faculty of Medicine, Macau University of Science and Technology, Macau SAR 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1758-8854","authenticated-orcid":false,"given":"Lui (Vincent)","family":"Chi-Hang","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.yapd.2017.03.012","article-title":"Biliary Atresia: Epidemiology, Genetics, Clinical Update, and Public Health Perspective","volume":"64","author":"Kassira","year":"2017","journal-title":"Adv. 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