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

Diogo Mosqueira; Stefania Pagliari; Koichiro Uto; Mitsuhiro Ebara; Sara Romanazzo; Carmen Escobedo-Lucea; Jun Nakanishi; Akiyoshi Taniguchi; Ornella Franzese; Paolo Di Nardo; Marie José T H Goumans; Enrico Traversa; Perpétua P C Pinto-Do-Ó; Takao Aoyagi; Giancarlo Forte

doi:10.1021/nn4058984

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

Diogo Mosqueira, Stefania Pagliari, Koichiro Uto, Mitsuhiro Ebara, Sara Romanazzo, Carmen Escobedo-Lucea, Jun Nakanishi, Akiyoshi Taniguchi, Ornella Franzese, Paolo Di Nardo, Marie José T H Goumans, Enrico Traversa, Perpétua P C Pinto-Do-Ó, Takao Aoyagi, Giancarlo Forte

Research output: Contribution to journal › Article › peer-review

125 Scopus citations

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. © 2014 American Chemical Society.

Original language	English (US)
Pages (from-to)	2033-2047
Number of pages	15
Journal	ACS Nano
Volume	8
Issue number	3
DOIs	https://doi.org/10.1021/nn4058984
State	Published - Feb 7 2014

Bibliographical note

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.

ASJC Scopus subject areas

General Physics and Astronomy
General Materials Science
General Engineering

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10.1021/nn4058984

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Mosqueira, D., Pagliari, S., Uto, K., Ebara, M., Romanazzo, S., Escobedo-Lucea, C., Nakanishi, J., Taniguchi, A., Franzese, O., Di Nardo, P., Goumans, M. J. T. H., Traversa, E., Pinto-Do-Ó, P. P. C., Aoyagi, T., & Forte, G. (2014). Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure. ACS Nano, 8(3), 2033-2047. https://doi.org/10.1021/nn4058984

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title = "Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure",

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. {\textcopyright} 2014 American Chemical Society.",

author = "Diogo Mosqueira and Stefania Pagliari and Koichiro Uto and Mitsuhiro Ebara and Sara Romanazzo and Carmen Escobedo-Lucea and Jun Nakanishi and Akiyoshi Taniguchi and Ornella Franzese and {Di Nardo}, Paolo and Goumans, {Marie Jos{\'e} T H} and Enrico Traversa and Pinto-Do-{\'O}, {Perp{\'e}tua P C} and Takao Aoyagi and Giancarlo Forte",

note = "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.",

year = "2014",

month = feb,

day = "7",

doi = "10.1021/nn4058984",

language = "English (US)",

volume = "8",

pages = "2033--2047",

journal = "ACS Nano",

issn = "1936-0851",

publisher = "American Chemical Society",

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Mosqueira, D, Pagliari, S, Uto, K, Ebara, M, Romanazzo, S, Escobedo-Lucea, C, Nakanishi, J, Taniguchi, A, Franzese, O, Di Nardo, P, Goumans, MJTH, Traversa, E, Pinto-Do-Ó, PPC, Aoyagi, T & Forte, G 2014, 'Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure', ACS Nano, vol. 8, no. 3, pp. 2033-2047. https://doi.org/10.1021/nn4058984

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 -

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

Abstract

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