| First Author | Totaro A | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15206 | PubMed ID | 28513598 |
| Mgi Jnum | J:250599 | Mgi Id | MGI:5920372 |
| Doi | 10.1038/ncomms15206 | Citation | Totaro A, et al. (2017) YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate. Nat Commun 8:15206 |
| abstractText | 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. |
