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dc.contributor.author | Aix, Esther | |
dc.contributor.author | Gutierrez-Gutierrez, Oscar | |
dc.contributor.author | Sanchez-Ferrer, Carlota | |
dc.contributor.author | Aguado, Tania | |
dc.contributor.author | Flores, Ignacio | |
dc.date.accessioned | 2017-10-30T13:15:44Z | |
dc.date.available | 2017-10-30T13:15:44Z | |
dc.date.issued | 2016 | |
dc.identifier | ISI:000377555500011 | |
dc.identifier.citation | J Cell Biol. 2016; 213(5):571-83 | |
dc.identifier.issn | 0021-9525 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5221 | |
dc.description.abstract | The molecular mechanisms that drive mammalian cardiomyocytes out of the cell cycle soon after birth remain largely unknown. Here, we identify telomere dysfunction as a critical physiological signal for cardiomyocyte cell-cycle arrest. We show that telomerase activity and cardiomyocyte telomere length decrease sharply in wild-type mouse hearts after birth, resulting in cardiomyocytes with dysfunctional telomeres and anaphase bridges and positive for the cell-cycle arrest protein p21. We further show that premature telomere dysfunction pushes cardiomyocytes out of the cell cycle. Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (G3 Terc(-/-)) show precocious development of anaphase-bridge formation, p21 up-regulation, and binucleation. In line with these findings, the cardiomyocyte proliferative response after cardiac injury was lost in G3 Terc(-/-) newborns but rescued in G3 Terc(-/-)/p21(-/-) mice. These results reveal telomere dysfunction as a crucial signal for cardiomyocyte cell-cycle arrest after birth and suggest interventions to augment the regeneration capacity of mammalian hearts. | |
dc.description.sponsorship | E. Aix was supported by a Formation de Profesorado Universitario predoctoral fellowship from the Ministerio de Educacion. C. Sanchez - Ferrer is supported by a predoctoral fellowship from the Ministerio de Economia y Competitividad. T. Aguado is a recipient of a Fundacion Cientifica Asociacion Espanola Contra el Cancer postdoctoral fellowship. This study was supported by grants from the Ministerio de Economia y Competitividad (SAF2012-38449 to I. Flores) and the Red Tematica de Investigation Cooperativa en Enfermedades Cardiovasculares (RD12/0042/0045 to I. Flores). The CNIC is supported by the Ministerio de Economia y Competitividad and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (Ministerio de Economia y Competitividad award SEV-2015-0505). | |
dc.language.iso | eng | |
dc.publisher | Rockefeller University Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | MOUSE HEART | |
dc.subject | TERMINAL TRANSFERASE | |
dc.subject | CARDIAC REGENERATION | |
dc.subject | OXIDATIVE STRESS | |
dc.subject | MAMMALIAN HEART | |
dc.subject | STEM-CELLS | |
dc.subject | PROLIFERATION | |
dc.subject | EXPRESSION | |
dc.subject | CANCER | |
dc.subject | MICE | |
dc.title | Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation | |
dc.type | journal article | |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 27241915 | |
dc.format.volume | 213 | |
dc.format.page | 571-583 | |
dc.identifier.doi | 10.1083/jcb.201510091 | |
dc.contributor.funder | Ministerio de Educación (España) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Asociación Española Contra el Cáncer | |
dc.contributor.funder | Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 1540-8140 | |
dc.relation.publisherversion | https://doi.org/10.1083/jcb.201510091 | |
dc.identifier.journal | Journal of Cell Biology | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Regeneración y envejecimiento | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | MINECO/ICTI2013-2016/SEV-2015-0505 | es_ES |
dc.rights.accessRights | open access | es_ES |