Screening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiation.

ABSTRACT: The cellular composition of barrier epithelia is essential to organismal homoeostasis. In particular, within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Yet, methods for the identification of biological targets regulating epithelial composition and function, and of small molecules modulating them, are lacking. Here we show that druggable biological targets and small-molecule regulators of intestinal stem cell differentiation can be identified via multiplexed phenotypic screening using thousands of miniaturized organoid models of intestinal stem cell differentiation into Paneth cells, and validated via longitudinal single-cell RNA-sequencing. We found that inhibitors of the

SUBMITTER: Mead BE 

PROVIDER: S-EPMC9046079 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature