Derivation of pluripotent epiblast stem cells from mammalian embryos

A new type of stem cell Human embryonic stem (ES) cells are potentially important in therapy because they are pluripotent, capable of differentiating into virtually any cell type given appropriate encouragement. One obstacle to progress in research on them has been the baffling differences between human and mouse ES cells. Now two groups working independently have created a new kind of pluripotent ES cell. Derived from mouse embryos after they implant in the wall of the uterus, these EpiSCs (epiblast stem cells) are distinct from 'classic' mouse ES cells and mirror key features of human ES cells. The discovery of EpiSCs should provide an important experimental model to accelerate the use of human ES cells in research and eventually perhaps, in therapy. A study revealing that pluripotent stem cells (EpiSCs) can be derived from the late epiblast layer of post-implantation mouse and rat embryos. To achieve this, a chemically defined, activin-containing culture medium known to be sufficient for long-term maintenance of human embryonic stem cells is used. These findings will help to understand the biological provenance of human embryonic stem cells. Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago 1 , 2 using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines 3 followed shortly thereafter by their derivation of human ES cells 4 . Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system fo