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

Handle URI:
http://hdl.handle.net/10754/563454
Title:
Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure
Authors:
Mosqueira, Diogo; Pagliari, Stefania; Uto, Koichiro; Ebara, Mitsuhiro; Romanazzo, Sara; Escobedo-Lucea, Carmen; Nakanishi, Jun; Taniguchi, Akiyoshi; Franzese, Ornella; Di Nardo, Paolo; Goumans, Marie José T H; Traversa, Enrico ( 0000-0001-6336-941X ) ; Pinto-Do-Ó, Perpétua P C; Aoyagi, Takao; Forte, Giancarlo
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.
KAUST Department:
Physical Sciences and Engineering (PSE) Division; Materials Science and Engineering Program; KAUST Solar Center (KSC); Materials for Energy Conversion and Storage (MECS) Lab
Publisher:
American Chemical Society (ACS)
Journal:
ACS Nano
Issue Date:
25-Mar-2014
DOI:
10.1021/nn4058984
PubMed ID:
24483337
Type:
Article
ISSN:
19360851
Sponsors:
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.
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Materials Science and Engineering Program; KAUST Solar Center (KSC)

Full metadata record

DC FieldValue Language
dc.contributor.authorMosqueira, Diogoen
dc.contributor.authorPagliari, Stefaniaen
dc.contributor.authorUto, Koichiroen
dc.contributor.authorEbara, Mitsuhiroen
dc.contributor.authorRomanazzo, Saraen
dc.contributor.authorEscobedo-Lucea, Carmenen
dc.contributor.authorNakanishi, Junen
dc.contributor.authorTaniguchi, Akiyoshien
dc.contributor.authorFranzese, Ornellaen
dc.contributor.authorDi Nardo, Paoloen
dc.contributor.authorGoumans, Marie José T Hen
dc.contributor.authorTraversa, Enricoen
dc.contributor.authorPinto-Do-Ó, Perpétua P Cen
dc.contributor.authorAoyagi, Takaoen
dc.contributor.authorForte, Giancarloen
dc.date.accessioned2015-08-03T11:51:55Zen
dc.date.available2015-08-03T11:51:55Zen
dc.date.issued2014-03-25en
dc.identifier.issn19360851en
dc.identifier.pmid24483337en
dc.identifier.doi10.1021/nn4058984en
dc.identifier.urihttp://hdl.handle.net/10754/563454en
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.en
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.en
dc.publisherAmerican Chemical Society (ACS)en
dc.subjectadult cardiac progenitor cellen
dc.subjectcardiac differentiationen
dc.subjectmechano- transductionen
dc.subjectsubstrate nanotopographyen
dc.subjectYAP/TAZen
dc.titleHippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructureen
dc.typeArticleen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentMaterials Science and Engineering Programen
dc.contributor.departmentKAUST Solar Center (KSC)en
dc.contributor.departmentMaterials for Energy Conversion and Storage (MECS) Laben
dc.identifier.journalACS Nanoen
dc.contributor.institutionNatl Inst Mat Sci, Biomat Unit, Int Ctr Mat Nanoarchitecton MANA, Tsukuba, Ibaraki, Japanen
dc.contributor.institutionUniv Porto, Inst Engn Biomed INEB, P-4100 Oporto, Portugalen
dc.contributor.institutionJapan Soc Promot Sci, Tokyo, Japanen
dc.contributor.institutionUniv Helsinki, Acad Finland, Div Pharmaceut Biosci, Ctr Drug Res CDR, Helsinki, Finlanden
dc.contributor.institutionUniv Roma Tor Vergata, Dept Syst Med, Rome, Italyen
dc.contributor.institutionUniv Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italyen
dc.contributor.institutionLeiden Univ, Dept Mol Cell Biol, Med Ctr, Leiden, Netherlandsen
dc.contributor.institutionSt Annes Univ Hosp, Int Clin Res Ctr, Integrated Ctr Cellular Therapy & Regenerat Med, Brno, Czech Republicen
kaust.authorTraversa, Enricoen

Related articles on PubMed

All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.