5 years ago

YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate

YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate
Stefano Piccolo, Luca Azzolin, Antonio Totaro, Francesca Zanconato, Michelangelo Cordenonsi, Martina Castellan, Stefano Giulitti, Giusy Battilana
How the behaviour of somatic stem cells (SCs) is influenced by mechanical signals remains a black-box in cell biology. Here we show that YAP/TAZ regulation by cell shape and rigidity of the extracellular matrix (ECM) dictates a pivotal SC decision: to remain undifferentiated and grow, or to activate a terminal differentiation programme. Notably, mechano-activation of YAP/TAZ promotes epidermal stemness by inhibition of Notch signalling, a key factor for epidermal differentiation. Conversely, YAP/TAZ inhibition by low mechanical forces induces Notch signalling and loss of SC traits. As such, mechano-dependent regulation of YAP/TAZ reflects into mechano-dependent regulation of Notch signalling. Mechanistically, at least in part, this is mediated by YAP/TAZ binding to distant enhancers activating the expression of Delta-like ligands, serving as ‘in cis’ inhibitors of Notch. Thus YAP/TAZ mechanotransduction integrates with cell–cell communication pathways for fine-grained orchestration of SC decisions.

Publisher URL: http://www.nature.com/articles/ncomms15206

DOI: 10.1038/ncomms15206

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