Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.618552
Keywords
organoids; epigenetic modifiers; intestinal stem cell biology; bioimage analysis; PRMT1; EP300; CREBBP
Categories
Funding
- Norwegian Research Council [274760, 270068, 248810/O70]
- Norwegian Research Council (Centre of Excellence grant) [223255/F50]
- Norwegian Cancer Society [182767]
- H2020 CORBEL [PID6031]
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By developing a semi-automated organoid screening method, researchers identified several targets that affect epithelial cell differentiation, including HDACs, EP300/CREBBP, LSD1, and type I PRMTs, which were verified by complementary methods. The study also showed that inhibiting type I PRMTs promotes enhanced epithelial differentiation, blocking adenoma growth while not affecting normal organoid cultures.
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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