On closer inspection we identified numerous differences in DNA methylation between ES cells and iPSCs. In terms of mCG, reprogramming generated hundreds of differentially methylated regions, most associated with CG islands and genes, and seeming to represent both memory of the somatic cell DNA methylation patterns as well as iPSC-specific DNA methylation patterns. Notably, many of the CG-DMRs were shared between independent iPSC lines, indicating that these loci are inherently susceptible to aberrant methylation in the reprogramming process. Further, the presence of unique CG-DMRs in each iPSC line indicates that in addition to the aforementioned susceptible regions, there may be a stochastic element to reprogramming that results in interclone variability. Lastly, both somatic memory and iDMRs can be transmitted at high frequency through differentiation.
