RT Journal Article SR Electronic T1 A semi-automated organoid screening method demonstrates epigenetic control of intestinal epithelial differentiation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.23.217414 DO 10.1101/2020.07.23.217414 A1 Jenny Ostrop A1 Rosalie Zwiggelaar A1 Marianne Terndrup Pedersen A1 François Gerbe A1 Korbinian Bösl A1 Håvard T. Lindholm A1 Alberto Díez-Sánchez A1 Naveen Parmar A1 Silke Radetzki A1 Jens Peter von Kries A1 Philippe Jay A1 Kim B. Jensen A1 Cheryl Arrowsmith A1 Menno J. Oudhoff YR 2020 UL http://biorxiv.org/content/early/2020/12/11/2020.07.23.217414.abstract AB 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 data, 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.Competing Interest StatementThe authors have declared no competing interest.