Signaling roadmap modulating naive and primed pluripotency

Human and mouse embryonic stem cells (ESCs) exhibit fundamental differences depicting two distinct states of pluripotency: naive and primed. Mouse ESCs (mESCs) are dependent on leukemia inhibitory factor for growth in culture and possess two active X chromosomes in their female cell lines and correspond to the naive state of pluripotency. Human ESCs (hESCs), however, closely resemble mouse epiblast stem cells and correspond to the primed state. Primed stem cells are dependent on basic FGF for growth and show differentiation bias into different cell lineages. Recent studies have revealed that these two pluripotent states can be interconverted by modifying the culture conditions, although unequivocal evidence for obtaining truly naive hESCs has not been found. Accurate identification of the functions of major pluripotency-related signaling pathways and their cross-talk networks should aid in the successful induction of stable naive pluripotency in human cells.