Evidence map›Paper›PMID 32145468›Full record

ArticleCellular and molecular gastroenterology and hepatology2020

A Novel Organoid Model of Damage and Repair Identifies HNF4α as a Critical Regulator of Intestinal Epithelial Regeneration.

Paula S Montenegro-Miranda, Jonathan H M van der Meer, Christine Jones, Sander Meisner, Jacqueline L M Vermeulen, Jan Koster, Manon E Wildenberg, Jarom Heijmans, Francois Boudreau, Agnes Ribeiro and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.9field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  9. Review
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  11. Human enteroids as a tool to study conventional and ultra-high dose rate radiation.Integrative biology : quantitative biosciences from nano to macro · 2023
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Intestinal Epithelial Regeneration in Response to Ionizing Irradiation.Journal of visualized experiments : JoVE · 2022
    Article
  17. Epithelial wound healing in inflammatory bowel diseases: the next therapeutic frontier.Translational research : the journal of laboratory and clinical medicine · 2021
    Review
  18. Article
  19. Article
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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

12 authors at 6 institutions in 4 countries.

Paula S Montenegro-MirandaTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Jonathan H M van der MeerTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Christine JonesDépartement d'Anatomie et de Biologie Cellulaire/Faculté de médecine et des sciences de la santé, Pavillon de Recherche Appliquée sur le Cancer, Sherbrooke, Canada.
Sander MeisnerTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Jacqueline L M VermeulenTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Jan KosterDepartment of Oncogenomics, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Manon E WildenbergTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Jarom HeijmansTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Francois BoudreauDépartement d'Anatomie et de Biologie Cellulaire/Faculté de médecine et des sciences de la santé, Pavillon de Recherche Appliquée sur le Cancer, Sherbrooke, Canada.
Agnes RibeiroCordeliers Research Center, Sorbonne Université, Université de Paris, INSERM, Paris, France.
Gijs R van den BrinkTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands; Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
Vanesa MuncanTytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands. Electronic address: v.muncan@amsterdamumc.nl.
Foundation for Liver and Gastrointestinal Research · NLUniversité de Sherbrooke · CAAmsterdam University Medical Centers · NLInserm · FRNetherlands Institute for Neuroscience · NLRoche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsRecent evidence has suggested that the intact intestinal epithelial barrier protects our body from a range of immune-mediated diseases. The epithelial layer has an impressive ability to reconstitute and repair upon damage and this process of repair increasingly is seen as a therapeutic target. In vitro models to study this process in primary intestinal cells are lacking.

methodsWe established and characterized an in vitro model of intestinal damage and repair by applying γ-radiation on small-intestinal organoids. We then used this model to identify novel regulators of intestinal regeneration.

resultsWe identified hepatocyte nuclear factor 4α (HNF4α) as a pivotal upstream regulator of the intestinal regenerative response. Organoids lacking Hnf4a were not able to propagate in vitro. Importantly, intestinal Hnf4a knock-out mice showed impaired regeneration after whole-body irradiation, confirming intestinal organoids as a valuable alternative to in vivo studies.

conclusionsIn conclusion, we established and validated an in vitro damage-repair model and identified HNF4α as a crucial regulator of intestinal regeneration. Transcript profiling: GSE141515 and GSE141518.

Indexed as

RegenerationAnimalsCells, CulturedHepatocyte Nuclear Factor 4Intestinal MucosaIntestine, SmallMaleMiceMice, KnockoutOrganoidsPrimary Cell CultureRadiation Injuries, ExperimentalHepatocyte Nuclear Factor 4Hnf4a protein, mouseIrradiationOrganoidsRegeneration

Identifiers

PMID32145468
PMCPMC7301200
OpenAlexW3009391993

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.