Stochastic processes in the development of pluripotency in vivo

The divergence of the pluripotent inner cell mass and extraembryonic trophectoderm from an apparently homogenous population of cells is a decisive event in mammalian preimplantation development. While three models have been proposed to explain early cellular differentiation in the mouse embryo, the initial cue generating asymmetry within the embryo remains elusive. Recently, unexpected heterogeneity in the expression of crucial transcription factors within the blastocyst has raised the intriguing possibility that a stochastic component is involved in lineage divergence. Unraveling the molecular dynamics and developmental function of the observed heterogeneity awaits further investigations at the single-cell level using quantitative live-imaging with appropriate reporter lines. The possible involvement of dynamic heterogeneity in the establishment, maintenance and resolution of pluripotency makes this topic highly relevant not only to developmental biology, but also to stem cell research and regenerative medicine. In this review, we discuss the possible involvement of stochastic processes in lineage divergence and the establishment of pluripotency in vivo, based on recent data from mouse embryology and stem cell research.