Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37883554.
- Also identified by DOI 10.1126/science.adi2246.
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Abstract
Enteroendocrine cells (EECs) are hormone-producing cells residing in the epithelium of stomach, small intestine (SI), and colon. EECs regulate aspects of metabolic activity, including insulin levels, satiety, gastrointestinal secretion, and motility. The generation of different EEC lineages is not completely understood. In this work, we report a CRISPR knockout screen of the entire repertoire of transcription factors (TFs) in adult human SI organoids to identify dominant TFs controlling EEC differentiation. We discovered ZNF800 as a master repressor for endocrine lineage commitment, which particularly restricts enterochromaffin cell differentiation by directly controlling an endocrine TF network centered on PAX4. Thus, organoid models allow unbiased functional CRISPR screens for genes that program cell fate.
Medical subject headings
- CRISPR-Cas Systems
- Enteroendocrine Cells
- Gene Expression Regulation
- Zinc Fingers
- Cell Lineage
- Repressor Proteins