Coke vs. Pepsi, Domino’s vs. Pizza Hut, Bud vs. Miller. Could you tell the difference them in a taste test, given that they are made in a slightly different way with slightly different starting materials? And in the end, if each option does the job they were designed to do (filling bellies!), will any slight differences matter?
These questions have been hounding pluripotent stem cell scientists, and not just food critics, in their comparisons between embryo-derived human embryonic stem cells (hESCs) and artificially reprogrammed human induced pluripotent stem cells (hiPSCs). The hope is that hiPSCs are truly equivalent to hESCs, and, therefore, they can be used to generate patient-specific cells and tissues for a wide range of ailments. However, multiple studies have suggested that hiPSCs are not transcriptionally, epigenetically, or functionally equivalent to hESCs, making them a poor substitute for the real thing.
Now, a new study from the laboratories of Konrad Hochedlinger and Peter J Park has shown that hESCs and hiPSCs might just be functionally equivalent. Their study compared global transcriptional and DNA methylation patterns for several hESCs with genetically matched hiPSCs generated via Sendai virus (SeV)-based reprogramming. This detailed comparison demonstrated that any transcriptional and epigenetic differences in hiPSCs were not due to their cellular origin or viral infection. In fact, the group found that most of the differences between matched hESCs and hiPSCs originated from variability in genetic background.
They did, however, identify a small number of genes whose expression differed between one pair of genetically matched hESCs and hiPSCs, but this pattern could not predict functional outcome measured using metabolic and in vitro-differentiation assays. Indeed, the group found only low expression levels of these genes in hESCs and hiPSCs, and this pattern showed no overlap with previously reported gene expression signatures, suggesting that this pattern was merely transcriptional “noise”.
This report will hopefully begin to extinguish any remaining doubts about the “worthiness” of hiPSCs and promote their treatment as transcriptionally, epigenetically, and functionally equals to hESCs! Check these results against your own, and see how your stem cells compare at Nature Biotechnology, 2015.