Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the early embryo and are widely used as in vitro model to study pluripotency and embryonic development. Recent advances in stem cell technology enabled the derivation of mouse ESCs in defined serum-free medium containing 2 kinase inhibitors (2i), so-called “ground state” pluripotent ESCs. The inhibitors are thought to maintain stemness by blocking the signalling activity of Erk and Gsk3. Information on signal transduction, transcriptional networks and epigenetic mechanisms acting in ground state pluripotent cells is scarce.The aim of my research group is to further define the ground state and to decipher regulatory mechanisms that maintain ESCs in the ground state. Current projects include: i) unravel the mode of action of the 2 kinase inhibitors in ground state pluripotency by state-of-the-art (phospho)proteomics on signaling pathways and nuclear factors; ii) decipher regulatory transcription factor networks and epigenetic mechanisms acting to maintain and to exit the ground state by genome-wide bisulfite sequencing and ChIP-seq; iii) use single cell RNA-Seq profiling to determine the role of (transcriptional) heterogeneity.