The quest for male germline stem cell markers: PAX7 gets ID'd

Abstract

Male germline or spermatogonial stem cells (SSCs) are conserved across many species and essential for uninterrupted production of sperm over long periods of reproductive life span. A better understanding of SSC biology provides limitless opportunities in male reproductive health, fertility preservation, and regenerative medicine. Although several potential markers define SSCs, not many definitive markers exist that are specific for a rare subset of SSCs that self-renew and have the ability to give rise to other progenitors, eventually contributing to all stages of spermatogenesis. In the September 2014 issue of the JCI, Aloisio and colleagues report that PAX7 is a new marker expressed uniquely in a rare subset of SSCs in mouse testes. PAX7+ cells fulfill all the criteria required for bona fide SSCs. Surprisingly, male germline-specific deletion of Pax7 indicates that it is dispensable for spermatogenesis.

Figure 1. A summary of known markers in various undifferentiated spermatogonial cells is shown.

Based on the report by Chan and colleagues, ID4 is the only known A_single spermatogonial marker (16). This ID4⁺ cell population has the ability to self-renew and to give rise to progenitors from which other transient progenitors and eventually differentiating germ cells are produced. Studies by Aloisio et al. have now identified PAX7⁺ as another true SSC marker. Three possibilities exist: (i) PAX7⁺ cells are one subset; (ii) ID4⁺ cells are another subset of nonoverlapping SSCs; or (iii) PAX7⁺ID4⁺ cells are an overlapping subset of A_single spermatogonia. Known markers of spermatogonia include ID4, undifferentiated embryonic cell transcription factor 1 (UTF1), GDNF family receptor αv1 (GFRα1), nanos homolog 2 (NANOS2), neurogenin 3 (NEUROG3), lin-28 homolog A (LIN28A), FOXO1, spalt-like transcription factor 4 (SALL4), and promyelocytic leukemia zinc finger (PLZF). Figure modified with permission from Genes & Development (16).