Transcription factor reprogramming differs markedly from nuclear transfer, particularly with regard to DNA demethylation, which commences immediately upon transfer of a somatic nucleus into ooplasm14, but occurs over days to weeks during the derivation of iPSC13. Because demethylation is a slow and inefficient process in factor-based reprogramming, we postulated that residual methylation might leave iPSC with an “epigenetic memory,” and that methylation might be more effectively erased by nuclear transfer. Here we compare the differentiation potential and genomic methylation of pluripotent stem cells (iPSC, ntESC, and fESC), and find evidence that iPSC indeed retain a methylation signature of their tissue of origin.
