Thursday, July 31, 2014
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Inhibition of notch
signaling and the histone methyltransferase DOT1L
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.
Published online July 31, 2014
Patent and licensing status
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
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