hiPSC lines whereas HUES3-derived hESC subclones clustered with HUES3-derived hiPSC lines. Consistent with this finding, overall transcriptional variation between groups of genetically matched hESC and hiPSC lines was significantly lower than that between unmatched cell lines (Supplementary Fig. 2B). Moreover, transcriptional variation within groups of genetically matched hiPSC or hESC lines was similar, indicating that hiPSCs and hESCs are equally variable (Supplementary Fig. 2C). Of note, the number of promoters differentially methylated between unmatched pluripotent cell lines was approximately twice as high (2,610) as that between matched pluripotent cell lines (1,205), suggesting that genetic background also influences epigenetic patterns in hESCs and hiPSCs (Supplementary Fig. 2D). We conclude that genetic background is a major driver of transcriptional and epigenetic differences between pluripotent cell lines, whereas the SeV reprogramming method introduces more subtle yet stable transcriptional changes in hiPSCs.
