de-novo-generation-of-somatic-stem-cells-by-yaptaz

<em>De Novo</em> Generation of Somatic Stem Cells by YAP/TAZ

Here we present protocols to isolate primary differentiated cells and turn them into stem/progenitor cells (SCs) of the same lineage by transient ...

University of Padua School of Medicine

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.

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

How the behavior of cells in living tissues is orchestrated according to tissue needs, size, and developmental stage is still poorly understood. Advances in these directions are essential to understand morphogenesis, 'self-organization' phenomena, to build new tissues for regenerative medicine or to reverse the changes in deranged organs, such as in cancer or in genetic disorders. This review outlines a new scenario by which the crosstalk between the Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) transcription factors and Notch signaling influences cell self-renewal, stem cell differentiation, cell fate decisions, epithelial-stromal interactions, inflammation, morphogenesis, and large-scale gene oscillations.

Article	Year
YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate. Nature communications\| PubMed ID: 28513598	2017
Crosstalk between YAP/TAZ and Notch Signaling. Trends in cell biology\| PubMed ID: 29665979	2018

Antonio Totaro

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