dc.contributor.author | Cruz, Francisco Miguel | |
dc.contributor.author | Tome, Maria | |
dc.contributor.author | Bernal, Juan Antonio | |
dc.contributor.author | Bernad, Antonio | |
dc.date.accessioned | 2017-11-27T13:49:48Z | |
dc.date.available | 2017-11-27T13:49:48Z | |
dc.date.issued | 2015 | |
dc.identifier | ISI:000367150100036 | |
dc.identifier.citation | Cell Death Dis. 2015; 6:e1953 | |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5384 | |
dc.description.abstract | B 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.sponsorship | This 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.iso | eng | |
dc.publisher | Nature Publishing Group | |
dc.relation.isversionof | Publisher's version | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | CELL SELF-RENEWAL | |
dc.subject | RANDOMIZED PHASE-1 TRIAL | |
dc.subject | ACTIVATED PROTEIN-KINASE | |
dc.subject | INTESTINAL STEM-CELLS | |
dc.subject | MYOCARDIAL-INFARCTION | |
dc.subject | HEART | |
dc.subject | PATHWAY | |
dc.subject | CANCER | |
dc.subject | CARDIOMYOPATHY | |
dc.subject | CARDIOMYOCYTES | |
dc.title | miR-300 mediates Bmi1 function and regulates differentiation in
primitive cardiac progenitors | |
dc.type | Artículo | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 26512961 | |
dc.format.volume | 6 | |
dc.identifier.doi | 10.1038/cddis.2015.255 | |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Comunidad de Madrid | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | European Commission | |
dc.relation.publisherversion | https://doi.org/10.1136/10.1038/cddis.2015.255 | |
dc.identifier.journal | Cell Death & Differentiation | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Cardiomiopatías de origen genético | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Antiguos CNIC | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/242038 | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |