A regulatory circuitry driving a noradrenergic to mesenchymal transition highlights YAP/TAZ as critical players in neuroblastoma plasticity - PubMed
5 hours ago
- #Neuroblastoma Plasticity
- #YAP/TAZ Regulation
- #Epigenetic Remodeling
- High-risk neuroblastoma exhibits plasticity between noradrenergic and mesenchymal states with distinct transcriptional programs.
- YAP and TAZ are key regulators of the mesenchymal state, forming a core regulatory circuitry with TEAD, FOSL, and RUNX at mesenchymal-specific super-enhancers.
- YAP/TAZ gene signature increases during noradrenergic-to-mesenchymal transition and decreases during the reverse, with inhibition blocking proliferation and transition.
- Overexpression of YAP/TAZ in noradrenergic cells induces mesenchymal reprogramming via TEAD4 redistribution and super-enhancer rewiring, revealing a YAP/TAZ-TEAD4 axis controlling plasticity.