The exploration of pluripotency space: Charting cell state transitions in peri-implantation development

Pluripotent cells in the mammalian embryo undergo state transitions marked by changes in patterns of gene expression and developmental potential as they progress from pre-implantation through post-implantation stages of development. Recent studies of cultured mouse and human pluripotent stem cells (hPSCs) have identified cells representative of an intermediate stage (referred to as the formative state) between naive pluripotency (equivalent to pre-implantation epiblast) and primed pluripotency (equivalent to late post-implantation epiblast). We examine these recent findings in light of our knowledge of peri-implantation mouse and human development, and we consider the implications of this work for deriving human embryo models from pluripotent cells.