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A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation

Intestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools to accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated organoid screening method, which we applied to a library of highly specific chem...

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Autores principales: Ostrop, Jenny, Zwiggelaar, Rosalie T., Terndrup Pedersen, Marianne, Gerbe, François, Bösl, Korbinian, Lindholm, Håvard T., Díez-Sánchez, Alberto, Parmar, Naveen, Radetzki, Silke, von Kries, Jens Peter, Jay, Philippe, Jensen, Kim B., Arrowsmith, Cheryl, Oudhoff, Menno J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872100/
https://www.ncbi.nlm.nih.gov/pubmed/33575256
http://dx.doi.org/10.3389/fcell.2020.618552
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author Ostrop, Jenny
Zwiggelaar, Rosalie T.
Terndrup Pedersen, Marianne
Gerbe, François
Bösl, Korbinian
Lindholm, Håvard T.
Díez-Sánchez, Alberto
Parmar, Naveen
Radetzki, Silke
von Kries, Jens Peter
Jay, Philippe
Jensen, Kim B.
Arrowsmith, Cheryl
Oudhoff, Menno J.
author_facet Ostrop, Jenny
Zwiggelaar, Rosalie T.
Terndrup Pedersen, Marianne
Gerbe, François
Bösl, Korbinian
Lindholm, Håvard T.
Díez-Sánchez, Alberto
Parmar, Naveen
Radetzki, Silke
von Kries, Jens Peter
Jay, Philippe
Jensen, Kim B.
Arrowsmith, Cheryl
Oudhoff, Menno J.
author_sort Ostrop, Jenny
collection PubMed
description Intestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools to accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated organoid screening method, which we applied to a library of highly specific chemical probes to identify epigenetic regulators of intestinal epithelial biology. The role of epigenetic modifiers in adult stem cell systems, such as the intestinal epithelium, is still undefined. Based on this resource dataset, we identified several targets that affected epithelial cell differentiation, including HDACs, EP300/CREBBP, LSD1, and type I PRMTs, which were verified by complementary methods. For example, we show that inhibiting type I PRMTs, which leads enhanced epithelial differentiation, blocks the growth of adenoma but not normal organoid cultures. Thus, epigenetic probes are powerful tools to study intestinal epithelial biology and may have therapeutic potential.
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spelling pubmed-78721002021-02-10 A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation Ostrop, Jenny Zwiggelaar, Rosalie T. Terndrup Pedersen, Marianne Gerbe, François Bösl, Korbinian Lindholm, Håvard T. Díez-Sánchez, Alberto Parmar, Naveen Radetzki, Silke von Kries, Jens Peter Jay, Philippe Jensen, Kim B. Arrowsmith, Cheryl Oudhoff, Menno J. Front Cell Dev Biol Cell and Developmental Biology Intestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools to accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated organoid screening method, which we applied to a library of highly specific chemical probes to identify epigenetic regulators of intestinal epithelial biology. The role of epigenetic modifiers in adult stem cell systems, such as the intestinal epithelium, is still undefined. Based on this resource dataset, we identified several targets that affected epithelial cell differentiation, including HDACs, EP300/CREBBP, LSD1, and type I PRMTs, which were verified by complementary methods. For example, we show that inhibiting type I PRMTs, which leads enhanced epithelial differentiation, blocks the growth of adenoma but not normal organoid cultures. Thus, epigenetic probes are powerful tools to study intestinal epithelial biology and may have therapeutic potential. Frontiers Media S.A. 2021-01-21 /pmc/articles/PMC7872100/ /pubmed/33575256 http://dx.doi.org/10.3389/fcell.2020.618552 Text en Copyright © 2021 Ostrop, Zwiggelaar, Terndrup Pedersen, Gerbe, Bösl, Lindholm, Díez-Sánchez, Parmar, Radetzki, von Kries, Jay, Jensen, Arrowsmith and Oudhoff. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Ostrop, Jenny
Zwiggelaar, Rosalie T.
Terndrup Pedersen, Marianne
Gerbe, François
Bösl, Korbinian
Lindholm, Håvard T.
Díez-Sánchez, Alberto
Parmar, Naveen
Radetzki, Silke
von Kries, Jens Peter
Jay, Philippe
Jensen, Kim B.
Arrowsmith, Cheryl
Oudhoff, Menno J.
A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation
title A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation
title_full A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation
title_fullStr A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation
title_full_unstemmed A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation
title_short A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation
title_sort semi-automated organoid screening method demonstrates epigenetic control of intestinal epithelial differentiation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872100/
https://www.ncbi.nlm.nih.gov/pubmed/33575256
http://dx.doi.org/10.3389/fcell.2020.618552
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