Figure 3.

Global DNA methylation changes upon reprogramming. MSC (green), iP-MSC (blue), and ESC (red) were analyzed with the Infinium HumanMethylation450 BeadChip. (a) Histogram and (b) scatter plot analysis of DNA methylation levels revealed that many hemimethylated CpG sites become highly methylated upon reprogramming. (c) In average, this gain in methylation was observed in all gene regions, whereas both hypermethylation and hypomethylation were significantly enriched in (d) non-promoter and intergenic regions as well as in (e,f) shore regions. (g) Unsupervised principal component analysis demonstrated that iP-MSC clustered closely together and that their methylome was related to ESC. The two principal components PC1 and PC2 showed variances of 81.5 and 6.2%, respectively. (h) Furthermore, hierarchical cluster analysis demonstrated that iP-MSC clones (c) from the same donor (D) clustered always together. ESC, embryonic stem cell; iP-MSC, induced pluripotent-mesencymal stromal cell; UTR, untranslated region.