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Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F19%3A00071033" target="_blank" >RIV/00159816:_____/19:00071033 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/pii/S0142961219301474?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0142961219301474?via%3Dihub</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.biomaterials.2019.03.009" target="_blank" >10.1016/j.biomaterials.2019.03.009</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading

  • Original language description

    The mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells (MSCs). MSC fate decision can be unbalanced by controlling substrate mechanics, in turn altering the transmission of tension through cell cytoskeleton. MSCs have been proposed for orthopedic and reconstructive surgery applications. Thus, a tight control of their adipogenic potential is required in order to avoid their drifting towards fat tissue. Substrate mechanics has been shown to drive MSC commitment and to regulate YAP/TAZ protein shuttling and turnover. The mechanism by which YAP/TAZ co-transcriptional activity is mechanically regulated during MSC fate acquisition is still debated. Here, we design few bioengineering tools suited to disentangle the contribution of mechanical from biological stimuli to MSC adipogenesis. We demonstrate that the mechanical repression of YAP happens through its phosphorylation, is purely mediated by cell spreading downstream of substrate mechanics as dictated by dimensionality. YAP repression is sufficient to prompt MSC adipogenesis, regardless of a permissive biological environment, TEAD nuclear presence or focal adhesion stabilization. Finally, by harnessing the potential of YAP mechanical regulation, we propose a practical example of the exploitation of adipogenic transdifferentiation in tumors.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    20602 - Medical laboratory technology (including laboratory samples analysis; diagnostic technologies) (Biomaterials to be 2.9 [physical characteristics of living material as related to medical implants, devices, sensors])

Result continuities

  • Project

  • Continuities

    R - Projekt Ramcoveho programu EK

Others

  • Publication year

    2019

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    BIOMATERIALS

  • ISSN

    0142-9612

  • e-ISSN

  • Volume of the periodical

    205

  • Issue of the periodical within the volume

    N/A

  • Country of publishing house

    NL - THE KINGDOM OF THE NETHERLANDS

  • Number of pages

    17

  • Pages from-to

    64-80

  • UT code for WoS article

    000464486600006

  • EID of the result in the Scopus database