POU Class 5 Homeobox 1 (POU5F1), otherwise known as octamer-binding transcription factor 4 (OCT4) is a transcription factor of the Pit-Oct-Unc (POU) family whose gene is highly conserved between mouse, cows and humans (Pesce et al., 1998). Its expression in both mammalian ESCs and germ cells is well established (Okamoto et al., 1990, Rosner et al., 1990, Nichols et al., 1998, Pesce et al., 1998, Richards et al., 2004): it appears to prevent differentiation of stem cells, with its expression being downregulated as cells proceed along a differentiation pathway. It can be found in murine embryos as early as the 4-cell stage and is subsequently localised to the epiblast of the ICM (Pesce et al., 1998). Its importance in early embryogenesis has been demonstrated by the peri-implantation lethality of the homozygous knock-out genotype in mouse embryos due to lack of pluripotency of the ICM (Nichols et al., 1998). Furthermore, both human (Yu et al., 2007) and bovine (Nong et al., 2015) embryonic fibroblasts have been reprogrammed to become induced pluripotent stem cells (iPSCs) by introducing pluripotency genes, including POU5F1, into the differentiated cells.

As gastrulation occurs, POU5F1 expression becomes constrained to the germline until it is specifically located in PGCs. Murine studies targeting post-implantation POU5F1 expression by using a Cre/loxP system specific to PGCs have revealed that lack of POU5F1 leads to PGC apoptosis rather than differentiation (Kehler et al., 2004), indicating that it is essential for PGC survival, but not for maintaining PGCs in their dedifferentiated state. Furthermore, it has also been demonstrated to be critical for PGC specification (Okamura et al., 2008). In mice, once PGCs have entered meiosis, POU5F1 is downregulated (Pesce et al., 1998). Its expression is switched back on again just after birth in meiotically-arrested oocytes and persists until the late stages of oocyte maturation (Pesce et al., 1998). In contrast, human POU5F1 expression decreases over time: it is highly expressed in PGCs, but declines during the second trimester with expression limited to mitotic cortical germ cells and disappears when oocytes are undergoing folliculogenesis (Stoop et al., 2005, Anderson et al., 2007). This suggests that once oocytes are in close contact with granulosa cells and are undergoing meiosis, they are no longer capable of being pluripotent. In summary, given its presence in both stem cells and PGCs, POU5F1 seems an appropriate marker for a fGSC.