Journal ArticleDOI
Role of YAP/TAZ in mechanotransduction
Sirio Dupont,Leonardo Morsut,Mariaceleste Aragona,Elena Enzo,Stefano Giulitti,Michelangelo Cordenonsi,Francesca Zanconato,Jimmy Le Digabel,Mattia Forcato,Silvio Bicciato,Nicola Elvassore,Stefano Piccolo +11 more
Reads0
Chats0
TLDR
YAP/TAZ are identified as sensors and mediators of mechanical cues instructed by the cellular microenvironment and are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry.Abstract:
Cells perceive their microenvironment not only through soluble signals but also through physical and mechanical cues, such as extracellular matrix (ECM) stiffness or confined adhesiveness. By mechanotransduction systems, cells translate these stimuli into biochemical signals controlling multiple aspects of cell behaviour, including growth, differentiation and cancer malignant progression, but how rigidity mechanosensing is ultimately linked to activity of nuclear transcription factors remains poorly understood. Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals exerted by ECM rigidity and cell shape. This regulation requires Rho GTPase activity and tension of the actomyosin cytoskeleton, but is independent of the Hippo/LATS cascade. Crucially, YAP/TAZ are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry; conversely, expression of activated YAP overrules physical constraints in dictating cell behaviour. These findings identify YAP/TAZ as sensors and mediators of mechanical cues instructed by the cellular microenvironment.read more
Citations
More filters
Journal ArticleDOI
Magnetically Tuning Tether Mobility of Integrin Ligand Regulates Adhesion, Spreading, and Differentiation of Stem Cells.
TL;DR: A novel strategy to tune the tether mobility of RGD on substrate via magnetic force is demonstrated, showing that high RGD tether mobility delays the early adhesion and spreading of human mesenchymal stem cells (hMSCs), leading to compromised osteogenic differentiation at later stage.
Journal ArticleDOI
Receptor control in mesenchymal stem cell engineering
TL;DR: This Review highlights integrin–growth factor receptor crosstalk mechanisms in MSC growth and differentiation, and material design strategies to trigger the synergistic signalling of integrins and growth factor receptors.
Journal ArticleDOI
Mesenchymal stem cell and chondrocyte fates in a multishear microdevice are regulated by Yes-associated protein.
TL;DR: The connection between YAP and MSC/chondrocyte fates in a fluid flow-induced mechanical microenvironment is revealed and new insights are provided into the mechanisms by which mechanical cues regulate the fates of MSCs and chondroCytes.
Journal ArticleDOI
Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.
Jun Ha Hwang,Mi Ran Byun,A. Rum Kim,Kyungmin Kim,Hang Jun Cho,Yo Han Lee,Juwon Kim,Mi Gyeong Jeong,Eun Sook Hwang,Jeong Ho Hong +9 more
TL;DR: It is shown that ECM stiffness regulates MSC fate through ERK or JNK activation, and TAZ activation was induced by ERK/JNK activation on a stiff hydrogel because exposure to an ERKor JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECm stiffness-induced ERK-induced JNKactivation is important for TAZ-driven osteogenic differentiation.
Journal ArticleDOI
Exploiting Advanced Hydrogel Technologies to Address Key Challenges in Regenerative Medicine.
TL;DR: Here, it is addressed how controlled chemistries are allowing for precise engineering of spatial and time‐dependent properties in hydrogels with a look to how these materials will eventually translate to clinical applications.
References
More filters
Journal ArticleDOI
Matrix elasticity directs stem cell lineage specification.
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
Journal ArticleDOI
Geometric control of cell life and death.
TL;DR: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension.
Journal ArticleDOI
Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment
TL;DR: It is demonstrated that cell shape regulates commitment of human mesenchymal stem cells to adipocyte or osteoblast fate and mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.
Journal ArticleDOI
Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
Bin Zhao,Xiaomu Wei,Weiquan Li,Ryan S. Udan,Ryan S. Udan,Qian Yang,Joungmok Kim,Joungmok Kim,Joe Xie,Tsuneo Ikenoue,Jindan Yu,Li Li,Li Li,Pan Zheng,Keqiang Ye,Arul M. Chinnaiyan,Georg Halder,Georg Halder,Zhi Chun Lai,Kun-Liang Guan,Kun-Liang Guan +20 more
TL;DR: It is demonstrated that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway, and YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition.
Journal ArticleDOI
Local force and geometry sensing regulate cell functions.
Viola Vogel,Michael P. Sheetz +1 more
TL;DR: Tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms of eukaryotic cells.