MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM
- Barbara Pernaute1,
- Thomas Spruce1,4,
- Kimberley M. Smith2,
- Juan Miguel Sánchez-Nieto1,
- Miguel Manzanares3,
- Bradley Cobb2 and
- Tristan A. Rodríguez1
- 1British 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;
- 2Royal Veterinary College, London NW1 0TU, United Kingdom;
- 3Department of Cardiovascular Developmental and Repair, Centro Nacional de Investigaciones Cardiovasculares-CNIC, 28029 Madrid, Spain
- Corresponding author: tristan.rodriguez{at}imperial.ac.uk
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.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.245621.114.
Freely available online through the Genes & Development Open Access option.
- Received May 16, 2014.
- Accepted July 25, 2014.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0.
