An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate.

ABSTRACT: Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the transcriptional regulators that control the emergence of the mature intestinal phenotype remain largely unknown. Using mouse fetal and adult small intestinal organoids, we uncover transcriptional differences between the fetal and adult state and identify rare adult-like cells present in fetal organoids. This suggests that fetal organoids have an inherent potential to mature, which is locked by a regulatory program. By implementing a CRISPR-Cas9 screen targeting transcriptional regulators expressed in fetal organoids, we establish Smarca4

SUBMITTER: Hansen SL 

PROVIDER: S-EPMC10337909 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature