Two types of pluripotent stem cells can be derived from the mouse embryo, thal re present the naïve and primed states of pluripotency, respectively. They differ at the molecular, epigenetic and functional level. lnterestingly, EpiSCs show a striking resistance to reprogramming when their nuclei are transferred in the oocyte cytoplasm, compared to ESC nuclei: embryos reconstructed with EpiSC nuclei in thalcase often stop dividing at the 2-cell stage (day 2), while those reconstructed with ESC nuclei develop efficiently to the blastocyst stage. Remarkably, we observed thal replication is the main cellular mechanism altered in these embryos. We also noticed thalthe use of an HDACi (histone deacetylase inhibitor), thal helps chromatin remodeling, enhances the rate of cloned blastocysts obtained with EpiSC. This suggests thal the nuclear and chromatin architecture strongly differ between these these two types of pluripotent stem cells.