Pluripotency Deconstructed

Pluripotency denotes the flexible capacity of single cells to give rise to all somatic lineages and typically also the germline. Mouse ES cells and post-implantation epiblast-derived stem cells (EpiSC) are widely used pluripotent cell culture systems. These two invitro stem cell types have divergent characteristics. They are considered as representative of distinct developmental stages, distinguished by using the terms naive and primed. A binary description is an over-simplification, however. Here, we discuss an intermediate stage of pluripotency that we term formative. Formative pluripotency features a gene regulatory network switch from the naive state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification.