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Nat Commun. 2017 May 17;8:15206. doi: 10.1038/ncomms15206.

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

Author information

1
Department of Molecular Medicine (DMM), University of Padua School of Medicine, viale Colombo 3, Padua 35126, Italy.
2
Department of Industrial Engineering (DII), University of Padua, via Marzolo 9, Padua 35131, Italy.

Abstract

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.

PMID:
28513598
PMCID:
PMC5442321
DOI:
10.1038/ncomms15206
[Indexed for MEDLINE]
Free PMC Article

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