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

Cellular and Molecular Gastroenterology and Hepatology
Paula S Montenegro-MirandaVanesa Muncan

Abstract

Recent 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. We 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. We 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. In 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.

References

Nov 1, 1970·The British Journal of Radiology·H R WithersM M Elkind
May 3, 2000·Alimentary Pharmacology & Therapeutics·W K MacNaughton
Sep 14, 2002·Current Gastroenterology Reports·Mike M Bismar, Frank A Sinicrope
Jul 17, 2003·Genes & Development·Daniel PintoHans Clevers
Sep 17, 2004·The Journal of Investigative Dermatology. Symposium Proceedings·Christopher S Potten
Aug 8, 2007·Gastroenterology·Yuko Mori-AkiyamaBenoit de Crombrugghe
Apr 25, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jean-Philippe BabeuFrançois Boudreau
Aug 4, 2009·Journal of Cellular Physiology·Meritxell GironellaJuan Lucio Iovanna
Nov 17, 2009·Nature Genetics·UNKNOWN UK IBD Genetics ConsortiumDavid P Strachan
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Wenli LiuGriffin P Rodgers
Jun 4, 2011·Cell Death and Differentiation·J R MatthewsA R Clarke
Feb 11, 2014·Journal of Radiation Research·Motohiro YamauchiKazuo Yoshida
Apr 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Xin LiLei Shi
Jul 29, 2015·The American Journal of Pathology·Attila E FarkasAsma Nusrat
Dec 4, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Leesa L SampsonYi Zheng
Oct 21, 2016·Oncotarget·Uday B MaachaniAnita T Tandle
Jun 9, 2017·Cellular and Molecular Gastroenterology and Hepatology·Kyle StokesPhillip Karpowicz
Feb 6, 2018·Stem Cell Research & Therapy·Payel BhanjaSubhrajit Saha
Mar 29, 2018·Science·S Manfredo VieiraM A Kriegel

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Citations

Dec 8, 2020·Frontiers in Cell and Developmental Biology·William D ReesTheodore S Steiner
May 12, 2021·Scientific Reports·Bartolomeus J MeijerJarom Heijmans
Jun 15, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Cambrian Y LiuEugene B Chang

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Datasets Mentioned

BETA
GSE141515
GSE141518

Methods Mentioned

BETA
irradiated
flow cytometry
Assay

Software Mentioned

Ingenuity pathway analysis ( IPA
GraphPad Prism
Genome studio
R2
FlowJo
IPA
GraphPad

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