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;

Genes & Development
|September 4, 2014
PubMed

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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