The molecular underpinnings of totipotency

Embryonic stem (ES) cells are characterized by their functional potency and capacity to self-renew in culture. Historically, ES cells have been defined as pluripotent, able to make the embryonic but not the extraembryonic lineages (such as the yolk sac and the placenta). The functional capacity of ES cells has been judged based on their ability to contribute to all somatic lineages when they are introduced into an embryo. However, a number of recent reports have suggested that under certain conditions, ES cells, and other reprogrammed cell lines, can also contribute to the extraembryonic lineages and, therefore, can be said to be totipotent. Here, we consider the molecular basis for this totipotent state, its transcriptional signature and the signalling pathways that define it.