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Inhibition of notch signaling and the histone methyltransferase DOT1L (DOT1L) improves reprogramming of human somatic cells to induced pluripotent stem (iPS) cells

Mouse and human cell culture studies suggest the inhibition of notch signaling and DOT1L can improve reprogramming of somatic cells to safer iPS cells. In cultured mouse and human keratinocytes, multiple g-secretase inhibitors, which block notch signaling, improved the efficiency of iPS cell reprogramming. In cultured neonatal human keratinocytes, the combination of a notch inhibitor and a DOT1L inhibitor with two reprogramming factors that lack oncogenic potential increased the rate of iPS cell formation 10-fold compared with the notch inhibitor and two reprogramming factors. Next steps could include identifying a small molecule reprogramming cocktail for human cells that works in the absence of reprogramming factors.

SciBX 7(29); doi:10.1038/scibx.2014.879
Published online July 31, 2014

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Ichida, J.K. et al. Nat. Chem. Biol.; published online June 22, 2014;
Contact: Kevin Eggan, Harvard University, Cambridge, Mass.

Contact: Alexander Meissner, same affiliation as above

Contact: Hidenori Akutsu, National Research Institute for Child Health and Development, Tokyo, Japan