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Article Dans Une Revue Cellular and Molecular Gastroenterology and Hepatology Année : 2020

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

Résumé

Background & aims: 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. Methods: 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. Results: 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. Conclusions: 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.

Dates et versions

hal-04008590 , version 1 (28-02-2023)

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Paula Montenegro-Miranda, Jonathan H.M. van der Meer, Christine Jones, Sander Meisner, Jacqueline L.M. Vermeulen, et al.. A Novel Organoid Model of Damage and Repair Identifies HNF4α as a Critical Regulator of Intestinal Epithelial Regeneration. Cellular and Molecular Gastroenterology and Hepatology, 2020, 10 (2), pp.209-223. ⟨10.1016/j.jcmgh.2020.02.007⟩. ⟨hal-04008590⟩
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