A genome-scale CRISPR screen reveals factors regulating Wnt-dependent renewal of mouse gastric epithelial cells
Kazuhiro Murakami, Yumi Terakado, Kikue Saito, Yoshie Jomen, Haruna Takeda, Masanobu Oshima, Nick Barker
Abstract
Significance Wnt activation is critically important during both early development and throughout adulthood for the maintenance and regeneration of tissue-resident stem cells. However, the underlying mechanism regulating Wnt-dependent epithelial renewal and differentiation in the stomach remains poorly understood. Here we apply genome-scale CRISPR-Cas9 knockout screening to three-dimensional ex vivo stomach organoids to reveal important mechanistic insight into Wnt-dependent epithelial renewal in mouse gastric epithelia. Our organoid-based screening strategy can be readily applied to a wide variety of organoids derived from different sources, potentially providing important insights on multiple biological phenomena.