Molecular Mechanisms Underlying Pluripotency

Pluripotency and self renewal are the two primary characteristics of pluripotent stem cells (PSCs) [1]-[4]. Pluripotency refers to the capacity of a single cell to give rise to any cell type of an embryo or an adult animal [5],[6]. A mammalian organism is developed from a single fertilized egg, the zygote, in an extremely ordered and error-proof fashion [7]. The zygote and the subsequent 2 to 4-cell stage blastomere are considered to be totipotent since they can give rise to the entire fetus, including the embryo and the extra embryonic tissue such as the placenta and the umbilical cord (Fig.1) [7]. As embryo development proceeds to 8-cell stage and beyond depending on the species, the cells in the blastomere gradually lose their totipotency. At about embryonic day 3.5 (E3.5) in mouse (about E5 in human) the blastomere compacts into a blastocyst in which two distinct cell populations reside. Cells in the outer layer of the blastocyst form the trophectoderm (TE) which eventually give rise to the extra embryonic tissue, trophoblast of the placenta, whereas cells in the inside of the blastocyst form the inner cell mass (ICM). The ICM then gives rise to additional two lineages of cells, the primitive endoderm (PrEn or hypoblast) and the primitive ectoderm (PrEc or epiblast) (Fig.1). The PrEn produces the secondary extra embryonic tissues, such as yolk sac, allantois and amnion, while the PrEc gives rise to all three germ layers of the embryo, namely the ectoderm, the mesoderm and the endoderm (Fig.1). Although the extra embryonic tissues are indispensible for mammalian embryonic development, it is the ICM derived PrEc (or epiblast) cells that form all the cells of an embryo and adult animal, thus these cells are defined as pluripotent [5],[8].