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Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure.

Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure.

Figure Legend: “YAP/TAZ localization and function within patient-derived cardiac stem cells can be controlled by materials design. Based on our results, Hippo pathway effectors YAP and TAZ act as on/off switch controlling cell lineage specification in cardiac stem cells by perceiving the composition of the surrounding extracellular matrix. The possibility to modify the activity of these proteins (here YAP in green) in stem cells through materials design – in this case through micropatterned surfaces coated with fibronectin (white dashed line) – opens new perspectives in tissue engineering applications with autologous stem cells”.

Journal Reference

Mosqueira D, Pagliari S, Uto K, Ebara M, Romanazzo S, Escobedo-Lucea C, Nakanishi J, Taniguchi A, Franzese O, Di Nardo P, Goumans MJ, Traversa E, Pinto-do-Ó P, Aoyagi T, Forte G.

ACS Nano. 2014 ;8(3):2033-47.

Biomaterials Unit, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan.

 

Abstract

 

Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design.

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