Evidence map›Paper›PMID 32222998›Full record

ArticleHepatology (Baltimore, Md.)2021

Regional Differences in Human Biliary Tissues and Corresponding In Vitro-Derived Organoids.

Casey A Rimland, Samantha G Tilson, Carola M Morell, Rute A Tomaz, Wei-Yu Lu, Simone E Adams, Nikitas Georgakopoulos, Francisco Otaizo-Carrasquero, Timothy G Myers, John R Ferdinand and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Article
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  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025
    Review
  12. Gallbladder cholangiocyte organoids.Biology of the cell · 2025
    Review
  13. Article
  14. Review
  15. Review
  16. Organoids in biliary atresia.World journal of pediatric surgery · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 8 institutions in 2 countries.

Casey A RimlandWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-5187-6921
Samantha G Tilson *Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Carola M Morell *Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Rute A Tomaz *Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Wei-Yu LuMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Simone E AdamsWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Nikitas GeorgakopoulosDepartment of Surgery, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
Francisco Otaizo-CarrasqueroGenomic Technologies Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD.
Timothy G MyersGenomic Technologies Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD.ORCID 0000-0002-7059-5906
John R FerdinandDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Richard L GieseckImmunopathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD.ORCID 0000-0003-0200-581X
Fotios SampaziotisWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Olivia C TysoeWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-1061-1484
Alexander RossWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Judith M KraiczyDepartment of Paediatrics, University of Cambridge, Cambridge, United Kingdom.
Brandon WesleyWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Daniele MuraroWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Matthias ZilbauerDepartment of Paediatrics, University of Cambridge, Cambridge, United Kingdom.
Gabriel C OniscuEdinburgh Transplant Centre, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, United Kingdom.
Nicholas R F HannanDivision of Cancer and Stem Cells, School of Medicine, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, United Kingdom.
Stuart J ForbesMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0003-3715-2561
Kourosh Saeb-ParsyDepartment of Surgery, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
Thomas A WynnImmunopathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD.
Ludovic VallierWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Wellcome/MRC Cambridge Stem Cell Institute · GBUniversity of Cambridge · GBMRC Centre for Regenerative Medicine · GBNational Institute of Allergy and Infectious Diseases · USUniversity of North Carolina at Chapel Hill · USEdinburgh Royal Infirmary · GBNational Institutes of Health · USNorth Carolina State University · US

Funding

Infectious Diseases Research Technologies Core - BethesdaZICAI001051 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$226.1M
Department of HealthMedical Research Council DPFS grant MR/P016839/1Medical Research Council G0701448Medical Research Council MC_PC_12009Medical Research Council MC_PC_17230Medical Research Council MR/K017047/1Medical Research Council MR/P016839/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/N001540/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/R001987/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/T2T0419NIDDK NIH HHSWellcome Trust
6 · The paper itself

Abstract

BACKGROUND AND

aimsOrganoids provide a powerful system to study epithelia in vitro. 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. APPROACH AND

resultsOrganoids 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-rich repeat-containing G-protein-coupled receptor 5/prominin 1 and ductal markers KRT19/KRT7. However, RNA sequencing revealed that organoids conserve only a limited number of regional-specific markers corresponding to their location of origin. Of particular interest, down-regulation of biliary markers and up-regulation of cell-cycle 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.

conclusionsTaken 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.

Indexed as

AnimalsBileBile Ducts, ExtrahepaticBile Ducts, IntrahepaticCell DifferentiationCommon Bile DuctEpithelial CellsGallbladderGene Expression RegulationHumansKeratin-19LiverMiceOrganoidsRNA-SeqTissue and Organ ProcurementKeratin-19

Identifiers

PMID32222998
PMCPMC8641381
OpenAlexW3013894747

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.