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Updated: Apr 24, 2026

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM
Barbara Pernaute1, Thomas Spruce1, Kimberley M Smith2
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;
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.
Insights
MicroRNAs (miRNAs) regulate apoptosis in mammalian stem cells. Specific miRNA families fine-tune BIM protein levels, acting as a crucial buffer for cell survival during early development.
Area of Science:
- Stem cell biology
- Molecular biology
- Developmental biology
Background:
- Mammalian primed pluripotent stem cells exhibit high susceptibility to cell death due to a low apoptotic threshold.
- Mechanisms regulating this apoptotic threshold in stem cells are not well understood.
Purpose of the Study:
- To investigate the role of microRNA (miRNA)-mediated regulation in controlling apoptosis within the post-implantation epiblast.
- To identify specific miRNA families involved in regulating the apoptotic threshold in stem cells.
Main Methods:
- Analysis of miRNA-mediated gene regulation in mammalian stem cells.
- Investigating the impact of specific miRNA families on apoptotic pathways.
- Quantification of proapoptotic protein BIM expression levels.
Main Results:
- MicroRNA-mediated regulation is identified as a key mechanism controlling apoptosis in the post-implantation epiblast.
- Three miRNA families (miR-20, miR-92, and miR-302) were found to control the mitochondrial apoptotic machinery.
- These miRNAs fine-tune the expression levels of the proapoptotic protein BIM.
Conclusions:
- The identified miRNA families are essential for maintaining cell survival in stem cells.
- These miRNAs act as a buffer, balancing the stem cells' propensity for differentiation and cell death.
- Understanding this regulation is critical for stem cell biology and developmental processes.
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