YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28513598.
- Also identified by DOI 10.1038/ncomms15206 and PMC identifier 5442321.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Cell Lineage
- Epidermal Cells
- Intracellular Signaling Peptides and Proteins
- Phosphoproteins
- Receptors, Notch
- Stem Cells