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
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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
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Journal ArticleDOI
In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells
Henk-Jan Prins,A. Koen Braat,Debby Gawlitta,Wouter J.A. Dhert,David A. Egan,Estel Tijssen-Slump,Huipin Yuan,Paul J. Coffer,Henk Rozemuller,Anton C.M. Martens +9 more
TL;DR: In BMSCs, the additional increase in ALP levels over basal levels during in vitro osteogenic differentiation is predictive of in vivo performance, and this value was confirmed by analyzing "bulk-cultured" B MSCs from various bone marrow biopsies.
Forcing through Tumor Metastasis: The Interplay between Tissue Rigidity and Epithelial-Mesenchymal
Transition C. Wei,Jing Yang +1 more
TL;DR: A review of recent advances in the understanding of the role of tissue rigidity in tumor progression and metastasis, the mechanisms by which mechanical cues integrate with biochemical signals from the tumor microenvironment, and the underlying mechanotransduction pathways involved in tumor growth is presented in this paper.
Journal ArticleDOI
Fluid flows and forces in development: functions, features and biophysical principles
TL;DR: These insights suggest that biological flow determines many aspects of cell behavior and identity through a specific set of physical stimuli and signaling pathways.
Journal ArticleDOI
The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart.
TL;DR: The current status of knowledge of mechanotransduction signaling pathways in cardiac fibroblasts that culminate in pro-fibrotic gene expression are reviewed.
Journal ArticleDOI
Adaptable Fast Relaxing Boronate-Based Hydrogels for Probing Cell-Matrix Interactions.
TL;DR: Using human mesenchymal stem cells (hMSC) as a model, the fast relaxation matrix mechanics are found to promote cell–matrix interactions, leading to spreading and an increase in nuclear volume, and induce yes‐associated protein/PDZ binding domain nuclear localization at longer times.
References
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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.