CG-DMRs identified between iPSCs and ES cells may be categorized as either a failure to reprogram the progenitor somatic cell methylation patterns (somatic ‘memory’) or iPSC-specific DMRs (iDMRs) that are not observed in the progenitor somatic cells and ES cells. A recent study reported the retention of somatic cell DNA methylation patterns in early-passage (passage 4) mouse iPSCs that was sufficient to distinguish between iPSC lines derived from different progenitor cell types, and which was subsequently attenuated after further passages (10–16 in total)14. However, the iPSCs analysed here included relatively late-passage iPSC lines (15–65 passages; Supplementary Table 1), indicating that we are able to discriminate somatic DNA methylation patterns in iPSCs that are resistant to resetting to an ES-cell-like state. Comparison of iPSC lines to their respective progenitors revealed that 44–49% of CG-DMRs were aberrant with respect to ES cells (P value = 0.05) and reflected memory of the progenitor methylation state (Fig. 3b and Supplementary Fig. 10). Accordingly, 51–56% of the iPSC CG-DMRs could be classified as iDMRs, reflecting a methylation state dissimilar to the respective progenitor somatic cell and both ES cell lines (Fig. 3b and Supplementary Fig. 10).
