title: MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM.
abstract: 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.
authors.affiliation: British Heart Foundation Centre for Research Excellence, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London W12 0NN, United Kingdom;
authors.forename: Barbara
authors.initials: B
authors.lastname: Pernaute
authors.affiliation: British Heart Foundation Centre for Research Excellence, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London W12 0NN, United Kingdom;
authors.forename: Thomas
authors.initials: T
authors.lastname: Spruce
authors.affiliation: Royal Veterinary College, London NW1 0TU, United Kingdom;
authors.forename: Kimberley M
authors.initials: KM
authors.lastname: Smith
authors.affiliation: British Heart Foundation Centre for Research Excellence, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London W12 0NN, United Kingdom;
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Sánchez-Nieto
authors.affiliation: Department of Cardiovascular Developmental and Repair, Centro Nacional de Investigaciones Cardiovasculares-CNIC, 28029 Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Manzanares
authors.affiliation: Royal Veterinary College, London NW1 0TU, United Kingdom;
authors.forename: Bradley
authors.initials: B
authors.lastname: Cobb
authors.affiliation: British Heart Foundation Centre for Research Excellence, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London W12 0NN, United Kingdom; tristan.rodriguez@imperial.ac.uk.
authors.forename: Tristan A
authors.initials: TA
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins
keywords: Bim; Dicer; apoptosis; epiblast; microRNAs; pluripotency