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Lin, Lin; DeMartino, Jeff; Wang, Daisong; van Son, Gijs J. F.; van der Linden, Reinier; Begthel, Harry; Korving, Jeroen; Andersson-Rolf, Amanda; van den Brink, Stieneke; Lopez-Iglesias, Carmen; van de Wetering, Willine J.; Balwierz, Aleksandra; Margaritis, Thanasis; van de Wetering, Marc; Peters, Peter J.; Drost, Jarno; van Es, Johan H.; Clevers, Hans

Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation

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  • Medientyp: E-Artikel
  • Titel: Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation
  • Beteiligte: Lin, Lin; DeMartino, Jeff; Wang, Daisong; van Son, Gijs J. F.; van der Linden, Reinier; Begthel, Harry; Korving, Jeroen; Andersson-Rolf, Amanda; van den Brink, Stieneke; Lopez-Iglesias, Carmen; van de Wetering, Willine J.; Balwierz, Aleksandra; Margaritis, Thanasis; van de Wetering, Marc; Peters, Peter J.; Drost, Jarno; van Es, Johan H.; Clevers, Hans
  • Erschienen: American Association for the Advancement of Science (AAAS), 2023
  • Erschienen in: Science, 382 (2023) 6669, Seite 451-458
  • Sprache: Englisch
  • DOI: 10.1126/science.adi2246
  • ISSN: 0036-8075; 1095-9203
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.