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dc.contributor.authorCruz, Francisco Miguel 
dc.contributor.authorTome, Maria 
dc.contributor.authorBernal, Juan Antonio 
dc.contributor.authorBernad, Antonio 
dc.date.accessioned2017-11-27T13:49:48Z
dc.date.available2017-11-27T13:49:48Z
dc.date.issued2015
dc.identifierISI:000367150100036
dc.identifier.citationCell Death Dis. 2015; 6:e1953
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5384
dc.description.abstractB lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal.
dc.description.sponsorshipThis study was supported by grants from the Ministry of Science and Innovation (SAF2012-34327, PLE2009-0147, and PSE-010000-2009-3), the Comunidad Autonoma de Madrid (S2010/BMD-2420), the Instituto de Salud Carlos III (RETICS.TERCEL), and the European Commission (Proposal 242038) to AB, (BFU2012-35258 and RYC-2009-04341) to JAB, and fellowship FPU-AP2010-5951 to FMC. We thank JL Toran and S Mendez-Ferrer for critical discussions of the manuscript; RM Carmona for help with the animal procedure; Fatima Sanchez Cabo for statistic and bioinformatic assistance, and K. McCreath for editorial support.
dc.language.isoeng
dc.publisherNature Publishing Group 
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCELL SELF-RENEWAL
dc.subjectRANDOMIZED PHASE-1 TRIAL
dc.subjectACTIVATED PROTEIN-KINASE
dc.subjectINTESTINAL STEM-CELLS
dc.subjectMYOCARDIAL-INFARCTION
dc.subjectHEART
dc.subjectPATHWAY
dc.subjectCANCER
dc.subjectCARDIOMYOPATHY
dc.subjectCARDIOMYOCYTES
dc.titlemiR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID26512961
dc.format.volume6
dc.identifier.doi10.1038/cddis.2015.255
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderComunidad de Madrid 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderEuropean Commission 
dc.relation.publisherversionhttps://doi.org/10.1136/10.1038/cddis.2015.255
dc.identifier.journalCell Death & Differentiation
dc.repisalud.orgCNICCNIC::Grupos de investigación::Cardiomiopatías de origen genético
dc.repisalud.orgCNICCNIC::Grupos de investigación::Antiguos CNIC
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/242038es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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