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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation.
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.
Afiliación
  • Lin L; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
  • DeMartino J; Oncode Institute, Utrecht, Netherlands.
  • Wang D; Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
  • van Son GJF; Oncode Institute, Utrecht, Netherlands.
  • van der Linden R; Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
  • Begthel H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
  • Korving J; Oncode Institute, Utrecht, Netherlands.
  • Andersson-Rolf A; Oncode Institute, Utrecht, Netherlands.
  • van den Brink S; Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
  • Lopez-Iglesias C; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
  • van de Wetering WJ; Oncode Institute, Utrecht, Netherlands.
  • Balwierz A; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
  • Margaritis T; Oncode Institute, Utrecht, Netherlands.
  • van de Wetering M; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
  • Peters PJ; Oncode Institute, Utrecht, Netherlands.
  • Drost J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
  • van Es JH; Oncode Institute, Utrecht, Netherlands.
  • Clevers H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
Science ; 382(6669): 451-458, 2023 10 27.
Article en En | MEDLINE | ID: mdl-37883554
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Regulación de la Expresión Génica / Dedos de Zinc / Linaje de la Célula / Células Enteroendocrinas / Sistemas CRISPR-Cas Límite: Adult / Humans Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Regulación de la Expresión Génica / Dedos de Zinc / Linaje de la Célula / Células Enteroendocrinas / Sistemas CRISPR-Cas Límite: Adult / Humans Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos