A comparison of the transcriptional profiles of hESC subclones (hESC SCs and hESC GFPs), in vitro-differentiated fibroblasts and derivative hiPSCs by unsupervised clustering showed the largest differences between pluripotent cell lines and differentiated cell types, consistent with previous observations5,15,22,23 (Supplementary Fig. 2A). Likewise, global methylation analysis of representative samples by reduced representation bisulfite sequencing (RRBS) separated pluripotent cells from in vitro-differentiated fibroblasts, indicating distinct epigenetic states (Supplementary Fig. 1F). Notably, we observed a clear segregation of all pluripotent samples into two transcriptionally related groups, irrespective of whether cell lines were infected with SeV or not (Fig. 2D, expanded from Supplementary Fig. 2A). This segregation could not be explained by the cellular origin of cell lines from embryos (hESCs) or somatic cells (hiPSCs) but instead correlated with the genetic background of each line. That is, HUES2-derived hESC subclones clustered with HUES2-derived 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,
