Here we show that isogenic male hESC and hiPSC lines are transcriptionally highly similar to one another, suggesting that genetic background variability and possibly sex differences account for most of the previously reported gene expression differences between hESCs and hiPSCs. This conclusion is particularly relevant to studies where only a limited number of hESC lines or a single iPSC donor individual was used, as imbalances in genetic background and sex may further inflate transcriptional differences9,10,37,38. Our finding that a previously reported set of DEGs between 4 hiPSC lines derived from a single individual and 4 hESC lines separated our hESC and hiPSC lines by genetic background rather than cellular origin supports this conclusion (Fig. 5D).
