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

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Documents

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

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.

Original languageEnglish
Article number618552
JournalFrontiers in Cell and Developmental Biology
Volume8
Pages (from-to)1-20
ISSN2296-634X
DOIs
Publication statusPublished - 2021

    Research areas

  • bioimage analysis, CREBBP, EP300, epigenetic modifiers, intestinal stem cell biology, organoids, PRMT1

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