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

ABSTRACT:

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 wer

SUBMITTER: Montenegro-Miranda PS 

PROVIDER: S-EPMC7301200 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature