Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure
Di Nardo, Paolo
Goumans, Marie José T H
Pinto-Do-Ó, Perpétua P C
KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
Materials Science and Engineering Program
KAUST Solar Center (KSC)
Materials for Energy Conversion and Storage (MECS) Lab
MetadataShow full item record
AbstractStem 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. © 2014 American Chemical Society.
SponsorsThe present work was supported by the Japan Society for the Promotion of Science (JSPS) through the "Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)", by the World Premiere International (WPI) Research Center Initiative, by the "Nanotechnology Network Project" of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan and by the European Regional Development Fund - Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123). The contribution of The Netherlands Institute for Regenerative Medicine (NIRM) and FINSKIN Project no. 273689 from the Academy of Finland is also gratefully acknowledged. The authors are grateful to Dr. Isabel Amaral for critical discussion, Mr. Sjoerd Duim for immunohistochemistry analysis, and Mr. Gianluca Discenza and Mr. Massimiliano Massarelli for the advice with statistical analysis. Moreover, the authors would like to thank Dr. Elena Romano and the Center for Advanced Microscopy "Patrizia Albertano" of the University of Rome "Tor Vergata" for confocal image analysys. P.P.O. was supported by Ciencia 2007 and the FCTG Grant PTDC/SAU-ORG/118297/2010. C.E.L. was supported by the Academy of Finland. Financial supporters had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PublisherAmerican Chemical Society (ACS)
- Crosstalk between Hippo and TGFβ: Subcellular Localization of YAP/TAZ/Smad Complexes.
- Authors: Grannas K, Arngården L, Lönn P, Mazurkiewicz M, Blokzijl A, Zieba A, Söderberg O
- Issue date: 2015 Oct 23
- Role of extracellular matrix and YAP/TAZ in cell fate determination.
- Authors: Hao J, Zhang Y, Wang Y, Ye R, Qiu J, Zhao Z, Li J
- Issue date: 2014 Feb
- YAP/TAZ at the Roots of Cancer.
- Authors: Zanconato F, Cordenonsi M, Piccolo S
- Issue date: 2016 Jun 13
- A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis.
- Authors: Moroishi T, Park HW, Qin B, Chen Q, Meng Z, Plouffe SW, Taniguchi K, Yu FX, Karin M, Pan D, Guan KL
- Issue date: 2015 Jun 15
- [Regulation of differentiation of mesenchymal stem cells by the Hippo pathway effectors TAZ/YAP].
- Authors: Men T, Piao SH, Teng CB
- Issue date: 2013 Nov