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. TITLE=A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.618552 DOI=10.3389/fcell.2020.618552 ISSN=2296-634X ABSTRACT=

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.