Cells in the epiblast of the early amniote embryo are pluripotent. Loss of pluripotency occurs at the time of gastrulation, when the three germ layers are established through an epithelial-mesenchymal transition (EMT) that generates the mesoderm and endoderm. But are there changes in the pluripotent state of the epiblast prior to gastrulation? And, if so, how are these controlled? Guojun Sheng and colleagues set out to determine whether features of epiblast morphology regulate pluripotency, using both the early chick embryo and human pluripotent stem cells (hPSCs) as models. They uncover a previously unappreciated ‘partial mesenchymal-epithelial transition (MET)’, which involves specification of the basal membrane domain and changes in cell packing. This morphological transition is associated with, and required for, a change in the expression of pluripotency markers – the fully epithelialized late chick epiblast cells, and the equivalent cells in hPSC colonies, show reduced levels of, for example, NANOG and POU5F1. The authors demonstrate that this MET-associated so-called ‘pluripotency exit’ is regulated by integrin signalling and is reversible. Importantly, it is distinct both from the naïve to primed transition and from pluripotency loss at gastrulation, thus identifying another step in pluripotency regulation in the early embryo.
