"
Significance
Naïve embryonic stem cells are characterized by genome-wide low levels of cytosine methylation, a property that may
be intrinsic to their function. We found that retinol/retinoic acid (vitamin A) and ascorbate (vitamin C) synergistically
diminish DNA methylation levels and in doing so enhance the generation of naïve pluripotent stem cells. This is achieved
by two complementary mechanisms. Retinol increases cellular levels of TET proteins (which oxidize DNA methylation),
whereas ascorbate affords them greater activity by reducing cellular Fe3+ to Fe2+. This mechanistic insight is relevant
for the production of induced pluripotent stem cells used in regenerative medicine, and contributes to our understanding
of how the genome is connected to extrinsic and intrinsic signals.
"
http://www.pnas.org/...679113.full.pdf
