NANOG is another transcription factor expressed in both pluripotent stem cells and germ cells, thus rendering it a prospective marker of fGSCs. It is found in both mouse (Chambers et al., 2003, Mitsui et al., 2003) and human (Chambers et al., 2003, Richards et al., 2004) ESCs and, in conjunction with POU5F1, is critical to maintaining the cells in a pluripotent state of self-renewal with downregulation of NANOG coinciding with increased cell differentiation (Chambers et al., 2003, Clark et al., 2004). Its role in generating iPSCs from human (Yu et al., 2007) and bovine (Nong et al., 2015) fetal fibroblasts has also been demonstrated.

In the human embryo, NANOG expression is subsequently restricted to PGCs within the fetal ovary (Perrett et al., 2008) and in mice, it is expressed in proliferating and migrating PGCs until the time of meiotic entry (Chambers et al., 2003, Yamaguchi et al., 2005). It has been shown to be essential to migrating PGC survival in the mouse embryo, with inducible, specific knockdown of Nanog in PGCs of transgenic mice resulting in migratory PGC apoptosis and not differentiation (Yamaguchi et al., 2009). Yamaguchi et al. postulated that the cell death may be a result of downstream gene dysregulation, with Nanog-deficient PGCs demonstrating downregulation of genes including the DNA-binding protein inhibitor, Id1 (Yamaguchi et al., 2009). Therefore, NANOG is a marker of both ESCs and early, pre-meiotic PGCs.