Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophy
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- dc.contributor.author Pessina, Patriziaca
- dc.contributor.author Kharraz, Yacineca
- dc.contributor.author Jardí, Mercèca
- dc.contributor.author Fukada, So-ichiroca
- dc.contributor.author Serrano, Antonio L.ca
- dc.contributor.author Perdiguero, Eusebio, 1968-ca
- dc.contributor.author Muñoz Cánoves, Pura, 1962-ca
- dc.date.accessioned 2016-02-03T17:50:42Z
- dc.date.available 2016-02-03T17:50:42Z
- dc.date.issued 2015
- dc.description.abstract Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.ca
- dc.description.sponsorship The authors acknowledge funding from the Ministry of Economy and Competitiveness (MINECO)-Spain (SAF2012-38547, PI13/02512, and PLE2009-0124), Association Française Myopathies (AFM), E-Rare, Fundació Marató TV3, Muscular Dystrophy Association (MDA), European Commission Research and Innovation funding EU-FP7 (Myoage, Optistem, and Endostem), and Duchenne PP-NL. P.P. and Y.K. were partly supported by postdoctoral fellowships from AFM.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Pessina P, Kharraz Y, Jardí M, Fukada S, Serrano AL, Perdiguero E et al. Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophy. Stem Cell Reports. 2015; 4(6): 1046-1060. DOI 10.1016/j.stemcr.2015.04.007ca
- dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2015.04.007
- dc.identifier.issn 2213-6711
- dc.identifier.uri http://hdl.handle.net/10230/25730
- dc.language.iso engca
- dc.publisher Elsevierca
- dc.relation.ispartof Stem Cell Reports. 2015;4(6):1046-60
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223098
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223576
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/241440
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-38547
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/PLE2009-0124
- dc.rights © 2015 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ca
- dc.subject.other Teixits -- Cultiusca
- dc.subject.other Distròfia muscularca
- dc.title Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophyca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca