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  • Roos, Floris J.M.Erasmus University Medical Center,University of Cambridge (author)

Human branching cholangiocyte organoids recapitulate functional bile duct formation

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • Elsevier BV,2022

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:b61d9290-4889-4c3a-ba63-cad22f6e4e81
  • https://lup.lub.lu.se/record/b61d9290-4889-4c3a-ba63-cad22f6e4e81URI
  • https://doi.org/10.1016/j.stem.2022.04.011DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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  • van Tienderen, Gilles S.Erasmus University Medical Center (author)
  • Wu, HaoyuRadboud University Nijmegen (author)
  • Bordeu, IgnacioUniversity of Cambridge (author)
  • Vinke, DinaErasmus University Medical Center (author)
  • Albarinos, Laura MuñozErasmus University Medical Center (author)
  • Monfils, KathrynErasmus University Medical Center (author)
  • Niesten, SabrahErasmus University Medical Center (author)
  • Smits, RonErasmus University Medical Center (author)
  • Willemse, JorkeErasmus University Medical Center (author)
  • Rosmark, OskarLund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups(Swepub:lu)immu-ojh (author)
  • Westergren-Thorsson, GunillaLund 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(Swepub:lu)medk-gwt (author)
  • Kunz, Daniel J.University of Cambridge (author)
  • de Wit, MauriceErasmus University Medical Center (author)
  • French, Pim J.Erasmus University Medical Center (author)
  • Vallier, LudovicUniversity of Cambridge (author)
  • IJzermans, Jan N.M.Erasmus University Medical Center (author)
  • Bartfai, RichardRadboud University Nijmegen (author)
  • Marks, HendrikRadboud University Nijmegen (author)
  • Simons, Ben D.University of Cambridge (author)
  • van Royen, Martin E.Erasmus University Medical Center (author)
  • Verstegen, Monique M.A.Erasmus University Medical Center (author)
  • van der Laan, Luc J.W.Erasmus University Medical Center (author)
  • Erasmus University Medical CenterUniversity of Cambridge (creator_code:org_t)

Related titles

  • In:Cell Stem Cell: Elsevier BV29:5, s. 13-7941934-5909

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