The States of Pluripotency: Pluripotent Lineage Development in the Embryo and in the Dish

Figure 1

Aligning pluripotent cells in culture with the pluripotent lineage in the embryo. Lower panel. Embryogenesis in the mouse is shown from the 16-cell embryo, when the first distinction between inner and outer cells is seen, to the 6.75-day embryo, after pluripotent cell differentiation has commenced at gastrulation. Trophoblast is not shown in either egg cylinder stage embryo representations. The pluripotent lineage can be followed in blue. Upper panel. The proposed alignment of cell states captured in vitro with developmental stages of the embryo. EPL cells represent the developmental continuum achieved within aggregates without passage. Differentiation in EPL cells is not progressive and it is not anticipated that populations representative of gastrulation stage primitive ectoderm will be formed. EpiSC have been derived from blastocysts to late gastrulation stage embryos (8.25-day embryos, not shown). Characterisation of EpiSC has shown the majority of these lines to be late epiblast, aligned with a population present in the late gastrula, although there is some evidence that lines derived from ES cells in culture can adopt a mid-epiblast identity, denoted with the dashed line. Cell states have been aligned with a proposed nomenclature that can be used to define pluripotent cell states functionally.