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

Author

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  • Antonio Totaro

    (University of Padua School of Medicine)

  • Martina Castellan

    (University of Padua School of Medicine)

  • Giusy Battilana

    (University of Padua School of Medicine)

  • Francesca Zanconato

    (University of Padua School of Medicine)

  • Luca Azzolin

    (University of Padua School of Medicine)

  • Stefano Giulitti

    (University of Padua School of Medicine
    University of Padua)

  • Michelangelo Cordenonsi

    (University of Padua School of Medicine)

  • Stefano Piccolo

    (University of Padua School of Medicine)

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.

Suggested Citation

  • Antonio Totaro & Martina Castellan & Giusy Battilana & Francesca Zanconato & Luca Azzolin & Stefano Giulitti & Michelangelo Cordenonsi & Stefano Piccolo, 2017. "YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15206
    DOI: 10.1038/ncomms15206
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    Cited by:

    1. Sorosh Amiri & Camelia Muresan & Xingbo Shang & Clotilde Huet-Calderwood & Martin A. Schwartz & David A. Calderwood & Michael Murrell, 2023. "Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Melati S. Abdul Halim & Jennifer M. Dyson & Max M. Gong & Moira K. O’Bryan & Reza Nosrati, 2024. "Fallopian tube rheology regulates epithelial cell differentiation and function to enhance cilia formation and coordination," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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