Factors regulating pluripotency and differentiation in early mammalian embryos and embryo-derived stem cells.

Mammalian development relies on the cellular proliferation and precisely orchestrated differentiation processes. In preimplantation embryos preservation of the pluripotent state and timely onset of differentiation are secured by specific mechanisms involving such factors as OCT₄, NANOG, SOX₂, or SALL₄. The pluripotency-sustaining cellular machinery is operational not only in the cells of preimplantation embryos but also in embryo-derived embryonic stem cells and epiblast stem cells. However, certain variations in the execution of pluripotency exist and result in the differences not only between embryonic cells and stem cells of the same mammalian species, but also between those of different mammalian species, such as mouse, rat, bank vole, or humans. In this review we describe the involvement of exogenous stimuli (e.g., LIF, WNT, BMP, FGF, and Activin) and function of intrinsic factors (e.g., OCT₄, NANOG, SOX₂, SALL₄) in the regulation of pluripotency in mammalian preimplantation embryos and pluripotent stem cells derived from them. We also focus at the existence of species-specific differences at the level of growth factor requirements, signaling pathways, and transcription factors. Thus, we discuss differences in mechanisms which understanding is one of the necessary steps allowing establishment of methods of efficient derivation, defined in vitro culture conditions, and possible future therapeutic applications of pluripotent stem cells.