YAPTAZ and neuroblastoma cell plasticity [scRNA-Seq]

Here, we show that YAP, TAZ, and their target genes are marked by super-enhancers and are strongly and specifically expressed in mesenchymal tumor cells. We characterize a core regulatory circuitry containing YAP/TAZ, TEAD, FOSL and RUNX factors that controls gene expression linked to a mesenchymal identity in neuroblastoma.

Genetic or pharmacological inactivation of YAP/TAZ reduces cell proliferation of mesenchymal neuroblastoma cells. The expression of a YAP/TAZ gene signature fully correlates with a mesenchymal identity in several models exhibiting plasticity between noradrenergic and mesenchymal states. Whereas YAP/TAZ inhibition impairs the noradrenergic to mesenchymal transition, YAP and/or TAZ overexpression induces a mesenchymal shift traduced by transcriptional and functional reprogramming, accompanied by the repression of noradrenergic identity.