Figure 1.

Intrinsic markers essential for SSC self-renewal and differentiation. The transcription factor ID4 identifies a small population of A_single spermatogonia that are believed to be the true stem cells (Chan et al., 2014). The membrane receptors GFRA1 and RET bind the ligand GDNF, which is crucial for stem cell self-renewal (Meng et al., 2000; Hofmann et al., 2005; Naughton et al., 2006). ZBTB16 and POU5F1 are transcription factors expressed by SSCs and undifferentiated spermatogonia (Ohbo et al., 2003; Buaas et al., 2004; Costoya et al., 2004; Dann et al., 2008). Upon downregulation of CYP26B1, increased retinoic acid levels will stimulate germ cell expression of STRA8, which will induce them to differentiate and enter meiosis (Anderson et al., 2008). SOHLH1/2 and NGN3 are expressed at the boundary between A_aligned and A₁-A₄ differentiating spermatogonia, while KIT is a known marker of differentiating spermatogonia (Schrans-Stassen et al., 1999; Yoshida et al., 2006; Suzuki et al., 2012). ZBTB16 is an inhibitor of KIT, which therefore contributes in maintaining the undifferentiated state (Filipponi et al., 2007). Molecules discussed more in depth in the present review are marked in blue.