Dissecting the Role of the Stem Cell Niche in Driving Conversion Between Pluripotent States

Pluripotency is defined as the ability to develop into all tissues of the adult organism. In vivo, pluripotency exists only transiently in early embryogenesis. Despite its transience, remarkably, the pluripotent state can be stably maintained in vitro. While originally thought to exist stably in one state, pluripotency has recently been demonstrated to exist in at least two states; states defined by their distinct transcriptional networks and the extrinsic signals that maintain these networks. These extrinsic cues are provided either exogenously or endogenously in an autocrine or paracrine manner by the local microenvironment, or niche, composed of a heterogenous population of neighbouring cells. One state of pluripotency represents an earlier stage in development (early-stage pluripotency) than the other (primed pluripotency). While the characteristics of and the transitions between the two states are becoming better defined, the specific role of the niche remains poorly understood. Using mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (EpiSCs) as models of early-stage and primed pluripotency, respectively, we demonstrate the influence of the stem cell niche in driving the reversion of EpiSCs.Ph.D