MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM

Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in...

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Detalhes bibliográficos
Autores: Pernaute, Bárbara, Spruce, Thomas, Smith, Kimberley M., Sánchez-Nieto, Juan Miguel, Manzanares, Miguel, Cobb, Bradley, Rodríguez, Tristán A.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/415025
Acesso em linha:http://hdl.handle.net/10261/415025
https://api.elsevier.com/content/abstract/scopus_id/84906888758
Access Level:acceso abierto
Palavra-chave:Epiblast
Pluripotency
Apoptosis
microRNAs
Bim
Dicer
Descrição
Resumo:Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death.