1. A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation.
- Author
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Ostrop J, Zwiggelaar RT, Terndrup Pedersen M, Gerbe F, Bösl K, Lindholm HT, Díez-Sánchez A, Parmar N, Radetzki S, von Kries JP, Jay P, Jensen KB, Arrowsmith C, and Oudhoff MJ
- 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ostrop, Zwiggelaar, Terndrup Pedersen, Gerbe, Bösl, Lindholm, Díez-Sánchez, Parmar, Radetzki, von Kries, Jay, Jensen, Arrowsmith and Oudhoff.)
- Published
- 2021
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