Year: 2017
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms15206
Authors: Antonio Totaro, Martina Castellan, Giusy Battilana, Francesca Zanconato, Luca Azzolin, Stefano Giulitti, Michelangelo Cordenonsi, Stefano Piccolo
Institution: University of Padua
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2616658238