Effect of NIBR-LTSi treatment on gene expression in mouse intestinal organoids

The YAP/Hippo pathway is a key regulator of organ growth and size regulation and is involved in safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. We report on the gene expression changes associated with YAP activation by the selective small molecule LATS kinase inhibitor NIBR-LTSi in mouse intestinal organoids. We show that, LATS-LTSi activates YAP signalling, promotes proliferation, induces a regenerative phenotype and blocks differentiation. Mouse intestinal organoids were grown from single cells until crypt-villus structures emerged (96h). Subsequently, organoids where treated with 5uM NIBR-LTSi or DMSO respectively and harvested after 24 h for transcriptome analaysis by RNAseq.