We next asked whether the DEGs have functional consequences. We focused on two DEGs, LDHA and SLC2A1 (also known as GLUT1), because of their strong basal expression in hESCs and reduced expression in all hiPSCs (Fig.3C,D). Both gene products are involved in energy metabolism; LDHA plays an important role in glycolysis by catalyzing the conversion of pyruvate to lactate24,25, whereas SLC2A1 facilitates glucose uptake in cells26,27. Accordingly, LDHA and SLC2A1 are abundantly expressed in pluripotent cells, which produce energy through glycolysis28 (Fig. 3C). Based on the down-regulation of these two genes in all examined hiPSC lines compared to hESC lines by RNA-seq and qPCR analyses (Fig. 3E), we hypothesized that hiPSC lines might be less glycolytic than hESC GFP lines. However, neither lactate production nor glucose uptake levels differed between isogenic hiPSC and hESC GFP lines (Fig. 3F). Further, there was no difference in LDHA protein levels despite the observed transcriptional differences (Fig. 3G). Thus, at least two of the 49 DEGs seem not to translate into functional differences, possibly owing to posttranscriptional compensatory mechanisms.
