In this webinar, we explore the application of complex and biologically relevant model systems for drug screening, such as small intestinal organoids. We describe several processes used to infer regulatory genetic interactions and identify genes that regulate cell-fate transitions and maintain the balance between regeneration and homeostasis, unravelling previously unknown roles for several pathways, among them retinoic acid signalling.

We then characterise a crucial role for retinoic acid nuclear receptors in controlling exit from the regenerative state and driving enterocyte differentiation.

Finally, by combining quantitative imaging with RNA sequencing, we show the role of endogenous retinoic acid metabolism in initiating transcriptional programmes that guide the cell-fate transitions of intestinal epithelium and identify an inhibitor of the retinoid X receptor that improves intestinal regeneration in vivo.

Learning outcomes of this webinar:

• Learn how to upscale, streamline and automate intestinal organoid handling
• Learn how to image in complex three-dimensional (3D) model systems and how to approach big imaging datasets
• Understand the basics of multivariate analysis on image-inferred features