دورية أكاديمية
Human branching cholangiocyte organoids recapitulate functional bile duct formation.
| العنوان: | Human branching cholangiocyte organoids recapitulate functional bile duct formation. |
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| المؤلفون: | Roos, Floris JM, van Tienderen, Gilles S, Wu, Haoyu, Bordeu, Ignacio, Vinke, Dina, Albarinos, Laura Muñoz, Monfils, Kathryn, Niesten, Sabrah, Smits, Ron, Willemse, Jorke, Rosmark, Oskar, Westergren-Thorsson, Gunilla, Kunz, Daniel J, de Wit, Maurice, French, Pim J, Vallier, Ludovic, IJzermans, Jan NM, Bartfai, Richard, Marks, Hendrik, Simons, Ben D, van Royen, Martin E, Verstegen, Monique MA, van der Laan, Luc JW |
| بيانات النشر: | Elsevier BV Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute Department of Physics Student Department of Surgery - Sci Department of Applied Mathematics and Theoretical Physics //dx.doi.org/10.1016/j.stem.2022.04.011 Cell Stem Cell |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Bile Ducts, Cholangiocarcinoma, Epithelial Cells, Humans, Organoids, Transcriptome, branching morphogenesis, cholangiocyte organoids, cholangiocytes, disease modeling, embryonic bile duct development, intrahepatic bile duct |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/346018Test |
| DOI: | 10.17863/CAM.93440 |
| الإتاحة: | https://doi.org/10.17863/CAM.93440Test https://www.repository.cam.ac.uk/handle/1810/346018Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.1C12F906 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.93440 |
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