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Chunk #19 — DISCUSSION

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A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs.
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We identified only 49 DEGs that could distinguish hESCs and hiPSCs and 8 iDEGs that were dysregulated in a subset of hiPSC lines (Fig. 3C and 4A). This small number of genes contrasts with previous studies, which identified much larger numbers of DEGs when comparing unmatched hESCs and hiPSCs using a similar cutoff5-7,10,13,22,23. Of note, we found no evidence that two of the tested DEGs (LDHA and SLC2A1) and two of the tested iDEGs (IRX2 and DPP10) predict functional outcome, i.e., energy production or differentiation potential into neural cells or EBs. These results therefore suggest that hESC and hiPSC lines are equivalent after accounting for genetic background differences. We surmise that the remaining DEGs we detected between isogenic hESCs and hiPSCs might represent transcriptional noise from weakly expressed genes. In support of this notion, the vast majority of the 49 DEGs was expressed at relatively low levels in our hESCs and hiPSCs and showed no overlap with previously reported gene expression signatures. However, we cannot exclude that the lack of an obvious phenotype with the abovementioned assays could be due