Pluripotent cell states and fates in human embryo models

ABSTRACT Pluripotency, the capacity to generate all cells of the body, is a defining property of a transient population of epiblast cells found in pre-, peri- and post-implantation mammalian embryos. As development progresses, the epiblast cells undergo dynamic transitions in pluripotency states, concurrent with the specification of extra-embryonic and embryonic lineages. Recently, stem cell-based models of pre- and post-implantation human embryonic development have been developed using stem cells that capture key properties of the epiblast at different developmental stages. Here, we review early primate development, comparing pluripotency states of the epiblast in vivo with cultured pluripotent cells representative of these states. We consider how the pluripotency status of the starting cells influences the development of human embryo models and, in turn, what we can learn about the human pluripotent epiblast. Finally, we discuss the limitations of these models and questions arising from the pioneering studies in this emerging field.