Evidence map›Paper›PMID 38857990›Full record

ArticleGut2024

Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn's Disease.

Thomas W Dennison, Rachel D Edgar, Felicity Payne, Komal M Nayak, Alexander D B Ross, Aurelie Cenier, Claire Glemas, Federica Giachero, April R Foster, Rebecca Harris and 37 more

Erratum issuedAbstract read
In one paragraph

Article in Gut, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

  1. Whole-Mount Immunostaining of Human Intestinal Organoids.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Review
  3. Recent advancements and limitations of intestinal organoids for clinical applications.Progress in biomedical engineering (Bristol, England) · 2026
    Review
  4. Article
  5. Review
  6. The roles and heterogeneity of CD8International journal of molecular medicine · 2026
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. New approach methodologies in Crohn's disease link molecular disease subtypes to clinical outcomes.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  13. Review
  14. mFrontiers in immunology · 2026
    Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

47 authors.

Thomas W Dennison *Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0002-1449-7965
Rachel D Edgar *European Bioinformatics Institute, Cambridge, Cambridgeshire, UK.ORCID 0000-0001-5507-6078
Felicity Payne *Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0003-4228-581X
Komal M NayakCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Alexander D B RossCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Aurelie CenierDepartment of Paediatrics, University of Cambridge, Cambridge, UK.
Claire GlemasCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Federica GiacheroCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
April R FosterMilner Therapeutics Institute, University of Cambridge, Cambridge, UK.
Rebecca HarrisMilner Therapeutics Institute, University of Cambridge, Cambridge, UK.
Judith KraiczyDepartment of Paediatrics, University of Cambridge, Cambridge, UK.
Camilla SalvestriniDepartment of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals (CUH), Addenbrooke's, Cambridge, UK.
Georgia StavrouDepartment of Paediatrics, University of Cambridge, Cambridge, UK.
Franco TorrenteDepartment of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals (CUH), Addenbrooke's, Cambridge, UK.
Kimberley BrookDepartment of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals (CUH), Addenbrooke's, Cambridge, UK.
Claire TrayersDepartment of Paediatric and Perinatal Pathology, Cambridge University Hospitals (CUH), Addenbrooke's Hospital, Cambridge, UK.
Rasa ElmentaiteWellcome Sanger Institute, Hinxton, Cambridgeshire, UK.
Gehad YoussefMilner Therapeutics Institute, University of Cambridge, Cambridge, UK.
Bálint TélPediatric Center, MTA Center of Excellence, Semmelweis University, Budapest, Hungary.ORCID 0000-0003-2066-6494
Douglas James WintonCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Nefeli Skoufou-PapoutsakiCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Sam AdlerCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Philip BuflerDepartment of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Aline AzabdaftariDepartment of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Andreas JenkeDepartment of Neonatology and General Pediatrics, Children's Hospital Kassel, Kassel, Germany.
Natasha GDepartment of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals (CUH), Addenbrooke's, Cambridge, UK.
Natasha ThomasDepartment of Paediatrics, University of Cambridge, Cambridge, UK.
Erasmo MieleDepartment of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.ORCID 0000-0003-4498-7305
Abdulrahman Al-MohammadDepartment of Paediatrics, University of Cambridge, Cambridge, UK.
Greta GuardaFaculty of Biomedical Sciences, Institute for Research in Biomedicine (IRB), Università della Svizzera italiana, Bellinzona, Switzerland.
Subra KugathasanDepartment of Pediatrics, Emory University, Atlanta, GA, USA.
Suresh VenkateswaranDepartment of Pediatrics, Emory University, Atlanta, GA, USA.
Menna R ClatworthyMolecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Tomas Castro-DopicoMolecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Ondrej SuchanekMolecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Caterina StrisciuglioDepartment of Woman, Child ad General and Specialistic Surgery, University of Campania " Vanvitelli", Naples, Italy.
Marco GasparettoNorfolk and Norwich University Hospital, Jenny Lind Children's Hospital, Norwich, UK.
Seokjun LeeCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Xingze XuCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Erica BelloMilner Therapeutics Institute, University of Cambridge, Cambridge, UK.
Namshik HanMilner Therapeutics Institute, University of Cambridge, Cambridge, UK.
Daniel R ZerbinoEuropean Bioinformatics Institute, Cambridge, Cambridgeshire, UK.
Sarah A TeichmannWellcome Sanger Institute, Hinxton, Cambridgeshire, UK.
Josquin NysBioscience Asthma and Skin Immunity, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Robert HeuschkelDepartment of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals (CUH), Addenbrooke's, Cambridge, UK.
Francesca PerroneCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK mz304@cam.ac.uk fp385@cam.ac.uk.
Matthias ZilbauerCambridge Stem Cell Institute, University of Cambridge, Cambridge, UK mz304@cam.ac.uk fp385@cam.ac.uk.ORCID 0000-0002-7272-0547

Funding

Medical Research Council MC_PC_17230
6 · The paper itself

Abstract

objectiveEpigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis.

designWe generated 312 intestinal epithelial organoids (IEOs) from mucosal biopsies of 168 patients with CD (n=72), UC (n=23) and healthy controls (n=73). We performed genome-wide molecular profiling including DNAm, bulk as well as single-cell RNA sequencing. Organoids were subjected to gene editing and the functional consequences of DNAm changes evaluated using an organoid-lymphocyte coculture and a nucleotide-binding oligomerisation domain, leucine-rich repeat and CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model.

resultsWe identified highly stable, CD-associated loss of DNAm at major histocompatibility complex (MHC) class 1 loci including

conclusionsOur study has identified epigenetically regulated intestinal epithelial MHC-I as a novel mechanism in CD pathogenesis.

Indexed as

Crohn DiseaseDNA MethylationEpigenesis, GeneticIntestinal MucosaOrganoidsAdultAnimalsBiological Specimen BanksDisease Models, AnimalFemaleHistocompatibility Antigens Class IHumansIntracellular Signaling Peptides and ProteinsMaleMiceMice, KnockoutHistocompatibility Antigens Class IIntracellular Signaling Peptides and ProteinsCROHN'S DISEASEINFLAMMATORY BOWEL DISEASEINTESTINAL EPITHELIUMMETHYLATION

Identifiers

PMID38857990
PMCPMC11347221

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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.