SET KO causes ESCs to transition out of pluripotent state

The nuclear oncogene, SET, has been shown to be involved in many cellular processes, including as an inhibitor of PP2A and as a H1 histone chaperone. SET exists in two main isoforms, SETα and SETβ, the former being the predominant isoform in mouse embryonic stem cells (ESCs). In this study, I have investigated SET`s role in the pluripotency of ESCs by comparing data from stem cells in various states of pluripotency and from SET KO mouse ESCs. Using transciptomic data from 2i-cultured, LIF/serum-cultured ESCs and epiblast stem cells (EpiSCs), I have taken significant differentially expressed genes from each of these categories and looked at their gene expression via RNA-seq in SET KO cells, SET overexpressing cells and SET single-isoform KO cells. Complete KO of SET shifts ESCs into a more LIF/serum and EpiSC state, whereas SET overexpression and knockout of single-isoforms of SET has a less extreme affect on transcriptomic state. The transcriptomic change in knockouts of both isoforms of SET seem to correlate with a decrease in Nanog levels. Together with data showing that SET KO cells have a premature-differentiation phenotype, these results suggest that SET is at least partly responsible for the maintenance of the pluripotent state in mouse ESCs and that loss of SET causes ESCs to gain transcriptomic characteristics of pluripotent stem cells in a `confused` or `primed` state.