%0 Journal Article %A J. Trott %A D. A. Turner %A P. Hayward %A S. Borchia %A A. M. Mateus %A P. Rué %A A. Martinez Arias %T An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells %D 2013 %R 10.1101/000653 %J bioRxiv %P 000653 %X Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains a pending subject. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state after this period under the influence of a gradient of Activin/nodal or BMP signalling a decision between NECT and PS is made. Whilst cells emerge from pluripotency with an intrinsic competence for NECT fate, the competence for PS occurs over a discrete temporal window. Surprisingly Wnt signalling aids both PS and NECT fates in a context dependent manner. %U https://www.biorxiv.org/content/biorxiv/early/2013/11/18/000653.full.pdf