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| Item Type: | Article |
|---|---|
| Title: | A semi-automated organoid screening method demonstrates epigenetic control of intestinal epithelial differentiation |
| Creators Name: | Ostrop, J. and Zwiggelaar, R.T. and Terndrup Pedersen, M. and Gerbe, F. and Bösl, K. and Lindholm, H.T. and Díez-Sánchez, A. and Parmar, N. and Radetzki, S. and von Kries, J.P. and Jay, P. and Jensen, K.B. and Arrowsmith, C. and Oudhoff, M.J. |
| 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. |
| Keywords: | Organoids, Epigenetic Modifiers, Intestinal Stem Cell Biology, Bioimage Analysis, PRMT1, EP300, CREBBP, Animals, Mice |
| Source: | Frontiers in Cell and Developmental Biology |
| ISSN: | 2296-634X |
| Publisher: | Frontiers Media SA |
| Volume: | 8 |
| Page Range: | 618552 |
| Date: | 21 January 2021 |
| Official Publication: | https://doi.org/10.3389/fcell.2020.618552 |
| PubMed: | View item in PubMed |
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