| Autor: |
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, Gijs R. van den Brink, Vanesa Muncan |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 2, Pp 209-223 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2352-345X |
| DOI: |
10.1016/j.jcmgh.2020.02.007 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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