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dc.contributor.authorMosqueira, Diogo
dc.contributor.authorPagliari, Stefania
dc.contributor.authorUto, Koichiro
dc.contributor.authorEbara, Mitsuhiro
dc.contributor.authorRomanazzo, Sara
dc.contributor.authorEscobedo-Lucea, Carmen
dc.contributor.authorNakanishi, Jun
dc.contributor.authorTaniguchi, Akiyoshi
dc.contributor.authorFranzese, Ornella
dc.contributor.authorDi Nardo, Paolo
dc.contributor.authorGoumans, Marie José T H
dc.contributor.authorTraversa, Enrico
dc.contributor.authorPinto-Do-Ó, Perpétua P C
dc.contributor.authorAoyagi, Takao
dc.contributor.authorForte, Giancarlo
dc.date.accessioned2015-08-03T11:51:55Z
dc.date.available2015-08-03T11:51:55Z
dc.date.issued2014-02-07
dc.identifier.citationMosqueira, D., Pagliari, S., Uto, K., Ebara, M., Romanazzo, S., Escobedo-Lucea, C., … 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. doi:10.1021/nn4058984
dc.identifier.issn19360851
dc.identifier.pmid24483337
dc.identifier.doi10.1021/nn4058984
dc.identifier.urihttp://hdl.handle.net/10754/563454
dc.description.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.
dc.description.sponsorshipThe 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.
dc.publisherAmerican Chemical Society (ACS)
dc.subjectadult cardiac progenitor cell
dc.subjectcardiac differentiation
dc.subjectmechano- transduction
dc.subjectsubstrate nanotopography
dc.subjectYAP/TAZ
dc.titleHippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure
dc.typeArticle
dc.contributor.departmentKAUST Solar Center (KSC)
dc.contributor.departmentMaterial Science and Engineering Program
dc.contributor.departmentMaterials for Energy Conversion and Storage (MECS) Lab
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.identifier.journalACS Nano
dc.contributor.institutionNatl Inst Mat Sci, Biomat Unit, Int Ctr Mat Nanoarchitecton MANA, Tsukuba, Ibaraki, Japan
dc.contributor.institutionUniv Porto, Inst Engn Biomed INEB, P-4100 Oporto, Portugal
dc.contributor.institutionJapan Soc Promot Sci, Tokyo, Japan
dc.contributor.institutionUniv Helsinki, Acad Finland, Div Pharmaceut Biosci, Ctr Drug Res CDR, Helsinki, Finland
dc.contributor.institutionUniv Roma Tor Vergata, Dept Syst Med, Rome, Italy
dc.contributor.institutionUniv Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy
dc.contributor.institutionLeiden Univ, Dept Mol Cell Biol, Med Ctr, Leiden, Netherlands
dc.contributor.institutionSt Annes Univ Hosp, Int Clin Res Ctr, Integrated Ctr Cellular Therapy & Regenerat Med, Brno, Czech Republic
kaust.personTraversa, Enrico
dc.date.published-online2014-02-07
dc.date.published-print2014-03-25


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