As most of the DEGs between undifferentiated hESC GFP and hiPSC lines produced low-abundance transcripts that were not obviously connected through a common biological process (Fig. 3C), we examined genes that were dysregulated in only a subset of hiPSC lines, which we refer to as inconsistently differentially expressed genes (iDEGs) (Supplementary Fig. 3C). We have previously shown that iDEGs between isogenic mouse ESCs and iPSCs could predict full developmental potential of subsets of iPSC lines16. Applying the same principle to our human data set, we found that 34 genes were upregulated, whereas 27 genes were downregulated in some of the HUES2-derived hiPSC lines when compared to genetically matched hESC GFP lines. Similarly, 9 genes were upregulated and 32 genes were downregulated in some of the HUES3-derived hiPSC lines relative to matched hESC GFP controls (Supplementary Fig. 3C). Only eight iDEGs were dysregulated in both genetic backgrounds, and these were thus selected for further analysis (Fig. 4A and Supplementary Fig. 3C).
