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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Detalles Bibliográficos
Autores: Pernaute, Barbara, Spruce, Thomas, Smith, Kimberley M, Sánchez-Nieto, Juan Miguel, Manzanares, Miguel, Cobb, Bradley, Rodríguez, Tristan A
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7353
Acceso en línea:http://hdl.handle.net/20.500.12105/7353
Access Level:acceso abierto
Palabra clave:Animals
Apoptosis
Apoptosis Regulatory Proteins
Bcl-2-Like Protein 11
Cell Survival
Cells, Cultured
Gene Expression Profiling
Membrane Proteins
Mice
MicroRNAs
Mitochondria
Pluripotent Stem Cells
Proto-Oncogene Proteins
Gene Expression Regulation, Developmental
Descripción
Sumario: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.