Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production

Cardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue which maintains tissue integrity and function through the production and remodeling of the extracellular matrix (ECM). Under pathological conditions, CFbs can activate into myofibroblasts and prom...

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Autores: Pereira-Sousa, Daniel, Guillamat, Pau, Niro, Francesco, Vinarsky, Vladimir, Fernandes, Soraia, Cassani, Marco, Pagliari, Stefania, Trepat, Xavier, Rasponi, Marco, Oliver De La Cruz, Jorge, Forte, Giancarlo
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universidad de Oviedo (UNIOVI)
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:dnet:ubarcelona__::5b5c3c5121da4db7cf761ae899b3e42e
Acceso en línea:https://hdl.handle.net/2445/229701
Access Level:acceso abierto
Palabra clave:Bioengineering
Biomaterials
Biophysics
Biotecnología
Ceramics and composites
Ciências biológicas ii
Engineering, biomedical
General medicine
Materials science, biomaterials
Mechanics of materials
Nanoscience and nanotechnology
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spelling Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM productionPereira-Sousa, DanielGuillamat, PauNiro, FrancescoVinarsky, VladimirFernandes, SoraiaCassani, MarcoPagliari, StefaniaTrepat, XavierRasponi, MarcoOliver De La Cruz, JorgeForte, GiancarloBioengineeringBiomaterialsBiophysicsBiotecnologíaCeramics and compositesCiências biológicas iiEngineering, biomedicalGeneral medicineMaterials science, biomaterialsMechanics of materialsNanoscience and nanotechnologyCardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue which maintains tissue integrity and function through the production and remodeling of the extracellular matrix (ECM). Under pathological conditions, CFbs can activate into myofibroblasts and promote maladaptive ECM remodeling that may lead to heart failure. Yes-Associated Protein (YAP) - a key player in cardiac fibrosis onset - has been implicated in CFb activation but its role in coordinating the supracellular organization of CFbs and in shaping the instructive properties of the ECM remains poorly understood. We addressed these questions by generating CFbs from wild-type (WT) and YAP knockout (KO) human embryonic stem cells. YAP depletion reduced the expression of cardiogenic markers and altered the transcriptomic profile of ECM- and contractility-related genes. We further demonstrated that YAP expression is required for CFbs monolayer alignment, and its absence resulted in reduced ECM deposition, decreased anisotropy, and diminished force generation. Pharmacological inhibition of cell contractility closely mirrored YAP KO phenotype, suggesting that YAP regulates both monolayer organization and ECM structure through its control over contractility. ECM cross-seeding experiments confirmed the role of ECM as a structural guide for cellular alignment. Moreover, cardiomyocytes cultured on KO CFb-derived ECM exhibited impaired sarcomere organization and altered calcium dynamics. Together, these findings demonstrate that YAP activity in CFbs governs the structural and functional properties of the ECM, influencing both fibroblast alignment and cardiomyocyte activity. Moreover, they underscore the critical role of YAP in maintaining the supracellular organization and mechanical integrity of cardiac tissue.Elsevier B.V.2026info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2445/229701reponame:Dipòsit Digital de la UBinstname:Universidad de Oviedo (UNIOVI)Ingléshttps://doi.org/10.1016/j.biomaterials.2026.124205BIOMATERIALS, 2026, 333, 124205https://doi.org/10.1016/j.biomaterials.2026.124205http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:ubarcelona__::5b5c3c5121da4db7cf761ae899b3e42e2026-05-27T06:46:51Z
dc.title.none.fl_str_mv Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
title Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
spellingShingle Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
Pereira-Sousa, Daniel
Bioengineering
Biomaterials
Biophysics
Biotecnología
Ceramics and composites
Ciências biológicas ii
Engineering, biomedical
General medicine
Materials science, biomaterials
Mechanics of materials
Nanoscience and nanotechnology
title_short Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
title_full Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
title_fullStr Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
title_full_unstemmed Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
title_sort Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
dc.creator.none.fl_str_mv Pereira-Sousa, Daniel
Guillamat, Pau
Niro, Francesco
Vinarsky, Vladimir
Fernandes, Soraia
Cassani, Marco
Pagliari, Stefania
Trepat, Xavier
Rasponi, Marco
Oliver De La Cruz, Jorge
Forte, Giancarlo
author Pereira-Sousa, Daniel
author_facet Pereira-Sousa, Daniel
Guillamat, Pau
Niro, Francesco
Vinarsky, Vladimir
Fernandes, Soraia
Cassani, Marco
Pagliari, Stefania
Trepat, Xavier
Rasponi, Marco
Oliver De La Cruz, Jorge
Forte, Giancarlo
author_role author
author2 Guillamat, Pau
Niro, Francesco
Vinarsky, Vladimir
Fernandes, Soraia
Cassani, Marco
Pagliari, Stefania
Trepat, Xavier
Rasponi, Marco
Oliver De La Cruz, Jorge
Forte, Giancarlo
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bioengineering
Biomaterials
Biophysics
Biotecnología
Ceramics and composites
Ciências biológicas ii
Engineering, biomedical
General medicine
Materials science, biomaterials
Mechanics of materials
Nanoscience and nanotechnology
topic Bioengineering
Biomaterials
Biophysics
Biotecnología
Ceramics and composites
Ciências biológicas ii
Engineering, biomedical
General medicine
Materials science, biomaterials
Mechanics of materials
Nanoscience and nanotechnology
description Cardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue which maintains tissue integrity and function through the production and remodeling of the extracellular matrix (ECM). Under pathological conditions, CFbs can activate into myofibroblasts and promote maladaptive ECM remodeling that may lead to heart failure. Yes-Associated Protein (YAP) - a key player in cardiac fibrosis onset - has been implicated in CFb activation but its role in coordinating the supracellular organization of CFbs and in shaping the instructive properties of the ECM remains poorly understood. We addressed these questions by generating CFbs from wild-type (WT) and YAP knockout (KO) human embryonic stem cells. YAP depletion reduced the expression of cardiogenic markers and altered the transcriptomic profile of ECM- and contractility-related genes. We further demonstrated that YAP expression is required for CFbs monolayer alignment, and its absence resulted in reduced ECM deposition, decreased anisotropy, and diminished force generation. Pharmacological inhibition of cell contractility closely mirrored YAP KO phenotype, suggesting that YAP regulates both monolayer organization and ECM structure through its control over contractility. ECM cross-seeding experiments confirmed the role of ECM as a structural guide for cellular alignment. Moreover, cardiomyocytes cultured on KO CFb-derived ECM exhibited impaired sarcomere organization and altered calcium dynamics. Together, these findings demonstrate that YAP activity in CFbs governs the structural and functional properties of the ECM, influencing both fibroblast alignment and cardiomyocyte activity. Moreover, they underscore the critical role of YAP in maintaining the supracellular organization and mechanical integrity of cardiac tissue.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/229701
url https://hdl.handle.net/2445/229701
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1016/j.biomaterials.2026.124205
BIOMATERIALS, 2026, 333, 124205
https://doi.org/10.1016/j.biomaterials.2026.124205
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv reponame:Dipòsit Digital de la UB
instname:Universidad de Oviedo (UNIOVI)
instname_str Universidad de Oviedo (UNIOVI)
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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