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. We identified several targets, which were verified by complementary methods, including HDACs, EP300/CREBBP, LSD1, and type I PRMTs. Based on this resource data, we conclude that epigenetic modifiers are primarily involved in balancing maturation of the epithelium. Furthermore, we show that inhibiting type I PRMTs, which leads to epithelial maturation, 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 Statement
The authors have declared no competing interest.
Footnotes
Introduction, Discussion & Results section updated to clarify; Figure 1, 3 & 6 revised; Supplemental files updated.