Mammalian embryo comparison identifies novel pluripotency genes associated with the naïve or primed state

During early mammalian development, transient pools of pluripotent cells emerge that can be immortalised upon stem cell derivation. The pluripotent state, 'naïve' or 'primed', depends on the embryonic stage and derivation conditions used. Here we analyse the temporal gene expression patterns of mouse, cattle and porcine embryos at stages that harbour different types of pluripotent cells. We document conserved and divergent traits in gene expression, and identify predictor genes shared across the species that are associated with pluripotent states <i>in vivo</i> and <i>in vitro</i> Amongst these are the pluripotency-linked genes <i>Klf4</i> and <i>Lin28b</i> The novel genes discovered include naïve- (<i>Spic, Scpep1</i> and <i>Gjb5</i>) and primed-associated (<i>Sema6a</i> and <i>Jakmip2</i>) genes as well as naïve to primed transition genes (<i>Dusp6</i> and <i>Trip6</i>). Both <i>Gjb5</i> and <i>Dusp6</i> play a role in pluripotency since their knockdown results in differentiation and downregulation of key pluripotency genes. Our interspecies comparison revealed new insights of pluripotency, pluripotent stem cell identity and a new molecular criterion for distinguishing between pluripotent states in various species, including human.