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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Bibliographic Details
Published in:Genes & development 2014-09, Vol.28 (17), p.1873-1878
Main Authors: Pernaute, Barbara, Spruce, Thomas, Smith, Kimberley M, Sánchez-Nieto, Juan Miguel, Manzanares, Miguel, Cobb, Bradley, Rodríguez, Tristan A
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Bcl-2-Like Protein 11
Cell Survival - genetics
Cells, Cultured
Gene Expression Profiling
Gene Expression Regulation, Developmental
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
MicroRNAs - metabolism
Mitochondria - metabolism
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Research Communication
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.245621.114