Frontiers in Cell and Developmental Biology (Jan 2021)

A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation

  • Jenny Ostrop,
  • Rosalie T. Zwiggelaar,
  • Marianne Terndrup Pedersen,
  • Marianne Terndrup Pedersen,
  • François Gerbe,
  • Korbinian Bösl,
  • Håvard T. Lindholm,
  • Alberto Díez-Sánchez,
  • Naveen Parmar,
  • Silke Radetzki,
  • Jens Peter von Kries,
  • Philippe Jay,
  • Kim B. Jensen,
  • Kim B. Jensen,
  • Cheryl Arrowsmith,
  • Cheryl Arrowsmith,
  • Cheryl Arrowsmith,
  • Menno J. Oudhoff

DOI
https://doi.org/10.3389/fcell.2020.618552
Journal volume & issue
Vol. 8

Abstract

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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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