TY - JOUR
T1 - Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure
AU - Mosqueira, Diogo
AU - Pagliari, Stefania
AU - Uto, Koichiro
AU - Ebara, Mitsuhiro
AU - Romanazzo, Sara
AU - Escobedo-Lucea, Carmen
AU - Nakanishi, Jun
AU - Taniguchi, Akiyoshi
AU - Franzese, Ornella
AU - Di Nardo, Paolo
AU - Goumans, Marie José T H
AU - Traversa, Enrico
AU - Pinto-Do-Ó, Perpétua P C
AU - Aoyagi, Takao
AU - Forte, Giancarlo
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: The 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.
PY - 2014/2/7
Y1 - 2014/2/7
N2 - 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. © 2014 American Chemical Society.
AB - 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. © 2014 American Chemical Society.
UR - http://hdl.handle.net/10754/563454
UR - https://pubs.acs.org/doi/10.1021/nn4058984
UR - http://www.scopus.com/inward/record.url?scp=84896911335&partnerID=8YFLogxK
U2 - 10.1021/nn4058984
DO - 10.1021/nn4058984
M3 - Article
C2 - 24483337
SN - 1936-0851
VL - 8
SP - 2033
EP - 2047
JO - ACS Nano
JF - ACS Nano
IS - 3
ER -