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Human branching cho...
Human branching cholangiocyte organoids recapitulate functional bile duct formation
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- Roos, Floris J.M. (author)
- Erasmus University Medical Center,University of Cambridge
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- van Tienderen, Gilles S. (author)
- Erasmus University Medical Center
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- Wu, Haoyu (author)
- Radboud University Nijmegen
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- Bordeu, Ignacio (author)
- University of Cambridge
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- Vinke, Dina (author)
- Erasmus University Medical Center
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- Albarinos, Laura Muñoz (author)
- Erasmus University Medical Center
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- Monfils, Kathryn (author)
- Erasmus University Medical Center
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- Niesten, Sabrah (author)
- Erasmus University Medical Center
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- Smits, Ron (author)
- Erasmus University Medical Center
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- Willemse, Jorke (author)
- Erasmus University Medical Center
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- Rosmark, Oskar (author)
- Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups
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- Westergren-Thorsson, Gunilla (author)
- Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lung Biology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine
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- Kunz, Daniel J. (author)
- University of Cambridge
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- de Wit, Maurice (author)
- Erasmus University Medical Center
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- French, Pim J. (author)
- Erasmus University Medical Center
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- Vallier, Ludovic (author)
- University of Cambridge
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- IJzermans, Jan N.M. (author)
- Erasmus University Medical Center
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- Bartfai, Richard (author)
- Radboud University Nijmegen
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- Marks, Hendrik (author)
- Radboud University Nijmegen
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- Simons, Ben D. (author)
- University of Cambridge
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- van Royen, Martin E. (author)
- Erasmus University Medical Center
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- Verstegen, Monique M.A. (author)
- Erasmus University Medical Center
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- van der Laan, Luc J.W. (author)
- Erasmus University Medical Center
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 29:5, s. 13-794
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modeling of bile duct development and diseases. However, the cystic organoids lack the branching morphology of intrahepatic bile ducts (IHBDs). Here, we report establishing human branching cholangiocyte organoid (BRCO) cultures. BRCOs self-organize into complex tubular structures resembling the IHBD architecture. Single-cell transcriptomics and functional analysis showed high similarity to primary cholangiocytes, and importantly, the branching growth mimics aspects of tubular development and is dependent on JAG1/NOTCH2 signaling. When applied to cholangiocarcinoma tumor organoids, the morphology changes to an in vitro morphology like primary tumors. Moreover, these branching cholangiocarcinoma organoids (BRCCAOs) better match the transcriptomic profile of primary tumors and showed increased chemoresistance to gemcitabine and cisplatin. In conclusion, BRCOs recapitulate a complex process of branching morphogenesis in vitro. This provides an improved model to study tubular formation, bile duct functionality, and associated biliary diseases.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- branching morphogenesis
- cholangiocarcinoma
- cholangiocyte organoids
- cholangiocytes
- disease modeling
- embryonic bile duct development
- intrahepatic bile duct
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Roos, Floris J.M ...
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van Tienderen, G ...
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Wu, Haoyu
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Bordeu, Ignacio
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Vinke, Dina
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Albarinos, Laura ...
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show more...
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Monfils, Kathryn
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Niesten, Sabrah
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Smits, Ron
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Willemse, Jorke
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Rosmark, Oskar
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Westergren-Thors ...
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Kunz, Daniel J.
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de Wit, Maurice
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French, Pim J.
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Vallier, Ludovic
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IJzermans, Jan N ...
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Bartfai, Richard
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Marks, Hendrik
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Simons, Ben D.
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van Royen, Marti ...
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Verstegen, Moniq ...
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van der Laan, Lu ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Cell Stem Cell
- By the university
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Lund University