New cell lines from mouse epiblast share defining features with human embryonic stem cells

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. Mouse and human embryonic stem (ES) cells use different signalling pathways to maintain their pluripotent status. Now, a new kind of pluripotent ES cell is described. This cell type is derived from mouse embryos after they implant in the wall of the uterus, and shares many defining features with human ES cells, including signalling responses that control differentiation to somatic fates. The application of human embryonic stem (ES) cells in medicine and biology has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo before implantation in the uterus 1 , 2 , 3 , 4 , 5 . Here we show that cell lines can be derived from the epiblast, a tissue of the post-implantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblast-derived stem cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells. The EpiSC lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development.