However, the transcriptional response of Oct4, Nanog and Tet1 to the release of cell-to-cell contact is subordinate to silencing by promoter methylation, as cells from wt EBs do not reactivate these genes upon replating, regardless of LIF stimulation. Thus, although additional epigenetic pathways are known to corepress Oct4 and Nanog and may respond to cell adhesion conditions, our data show that DNA methylation is crucial for complete and permanent extinction of Oct4 and Nanog transcription and thus enforces canalization of developmental fate upon differentiation. Global inhibition of Dnmt activity was shown to facilitate reprogramming of differentiated somatic cells to pluripotency. However, this approach may have undesired effects, especially in the case of mechanism based inhibitors that lead to the formation of covalent and potentially mutagenic Dnmt-DNA adducts. Our observation that differentiated cells lacking only Dnmt1 efficiently revert to the ESC state suggests that transient and specific inhibition of Dnmt1 activity may be sufficient to promote conversion of differentiated cell types to the pluripotent state. However, this could also be counteracted by death of not yet dedifferentiated cells as Dnmt1 ablation in differentiated cells was shown to trigger apotosis at least in part mediated by p53. At the same time functional p53 inactivation has been shown to increase the efficiency of iPSC derivation by overcoming proliferative senescence of differentiated cells. Thus, combining transient functional inactivation of Dnmt1 and p53 may have a synergistic effect on the reprogramming efficiency. Indeed, p53 inactivation may favor rapid passive demethylation by increasing Lomitapide Mesylate proliferation rates and at the same time it may prevent death of not yet dedifferentiated cells. In conclusion, our results underscore a critical role of DNA methylation and Dnmts in restricting developmental potential by permanently sealing transcriptionally silent states, as in the case of the pluripotency genes Oct4 and Nanog and genes involved in the neuroectodermal lineage. In addition, our results lend support to transient Dnmt1 inhibition as an approach for improved reprogramming of differentiated cells to the pluripotent state, which in turn suggests functional p53 inactivation as a potentially synergistic strategy. Over the past years, the phenotypic and functional boundaries distinguishing the main cell subsets of the human immune system have become increasingly blurred. While it has already been well established that T cells may share some phenotypic and functional features with natural killer cells, more recent evidence also points to the existence of such overlap between NK cells and dendritic cells. NK cells have been shown capable of antigen presentation, a classical function of DCs. In mice, specialized NK cell subsets, collectively designated as ��natural killer dendritic cells��, have been identified that display a hybrid NK cell/DC phenotype and combine functional properties of NK cells and DCs. Conversely, evidence from both rodent and human studies is emerging that DCs may exhibit NK-like activity and play a direct role in Folinic acid calcium salt pentahydrate innate immunity as killer cells; in the literature, these cells are designated as ��killer DCs��. Such killer DCs that can combine both tumor antigen presentation function with direct tumoricidal activity are garnering increasing attention as potential new, multifunctional tools for cancer immunotherapy. Hitherto, monocyte-derived DCs represent the DC type most widely used in human immunotherapy trial protocols.