Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation.
Saved in:
| Title: | Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation. |
|---|---|
| Authors: | Lin, Lin, DeMartino, Jeff, Wang, Daisong, Son, Gijs J. F. van, Linden, Reinier van der, Begthel, Harry, Korving, Jeroen, Andersson-Rolf, Amanda, Brink, Stieneke van den, Lopez-Iglesias, Carmen, Wetering, Willine J. van de, Balwierz, Aleksandra, Margaritis, Thanasis, Wetering, Marc van de, Peters, Peter J., Drost, Jarno, Es, Johan H. van, Clevers, Hans |
| Source: | Science (pre-March 2025). 10/27/2023, Vol. 382 Issue 6669, p451-458. 8p. 1 Color Photograph, 3 Diagrams. |
| Subjects: | Transcription factors, CRISPRs, Enteroendocrine cells, Endocrine system, Small intestine, Cell differentiation |
| 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
|
Full text is not displayed to guests.
Login for full access.
|
|
| 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. [ABSTRACT FROM AUTHOR] |
|---|---|
| ISSN: | 00368075 |
| DOI: | 10.1126/science.adi2246 |
