New and renewed perspectives on embryonic stem cell pluripotency

Although "stem cell biology" is frequently described as a young field, the examination of pluripotency and its effects on embryonic cells has had an interesting and somewhat unusual history. After decades of research into the pluripotency of mammalian embryonic cells, the use of pluripotent cells came into prominence as mouse embryonic stem cells (ESC) provided the foundation of knockout mouse technology; however, the basic biology of pluripotency in embryonic cells was not extensively examined for roughly another twenty years until the creation of human embryonic stem cell lines. With the burgeoning potential of cell based therapies and roles of cancer stem cells in disease, understanding basic biological mechanisms regulating stem cell characteristics now presents great new opportunities. Therefore, it is not surprising that the underlying genetic and epigenetic forces allowing ESC to maintain pluripotency have been the focus of intense scientific scrutiny in recent years. In order to fully appreciate the importance of new discoveries regarding pluripotency in ESC, it is necessary to understand the role of pluripotency in normal embryonic development. The main purpose of this review is to highlight recent discoveries in the context of what was known about pluripotency and lineage commitment in the embryo prior to the bioinformatics and genomics age. In doing so we attempt to elucidate the importance and limitations of recent discoveries and identify important avenues for future research.