Cell Stem Cell
Volume 7, Issue 4, 8 October 2010, Pages 508-520
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Article
Apoptotic Caspases Regulate Induction of iPSCs from Human Fibroblasts

https://doi.org/10.1016/j.stem.2010.09.003Get rights and content
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Summary

The molecular mechanisms involved in the derivation of induced pluripotent stem cells (iPSCs) from differentiated cells are poorly understood. Here we report that caspases 3 and 8, two proteases associated with apoptotic cell death, play critical roles in induction of iPSCs from human fibroblasts. Activation of caspases 3 and 8 occurs soon after transduction of iPSC-inducing transcription factors. Oct-4, a key iPSC transcription factor, is responsible for the activation. Inhibition of caspase 3 or 8 in human fibroblast cells partially or completely (respectively) prevents the induction of iPSCs. Furthermore, retinoblastoma susceptibility (Rb) protein appears to be one of the factors that act downstream of the caspases. We propose that caspases are key facilitators of nuclear reprogramming in iPSC induction.

Highlights

► Caspases 3 and 8 are activated in iPSC induction ► Transduction of Oct-4 alone is sufficient to activate caspases 3 and 8 ► Inhibition of caspase 3 and 8 activation significantly impedes iPSC induction ► Retinoblastoma protein (Rb) acts downstream of caspases 3 and 8 in iPSC induction

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