The pluripotency factor LIN28 in monkey and human testis: a marker for spermatogonial stem cells?

Mammalian spermatogenesis is maintained by spermatogonial stem cells (SSCs). However, since evidentiary assays and unequivocal markers are still missing in non-human primates and man, the identity of primate SSCs is unknown. In contrast, in the mouse, germ cell transplantation studies functionally demonstrated the presence of SSCs. LIN28 is an RNA-binding pluripotent stem cell factor, which is also strongly expressed in undifferentiated mouse spermatogonia. By contrast, two recent reports indicated that LIN28 is completely absent from adult human testes. Here, we analysed LIN28 expression in marmoset monkey (Callithrix jacchus) and human testes during development and adulthood and compared it with the mouse. In the marmoset, LIN28 was strongly expressed in migratory PGCs and gonocytes. Strikingly, we found a rare LIN28-positive subpopulation of spermatogonia also in the adult marmoset testis. This was corroborated by western blotting and quantitative RT-PCR. Importantly, in contrast to previous publications, we found LIN28-positive spermatogonia also in normal adult human and additional adult non-human primate testes. Some seasonal breeders exhibit a degenerated (involuted) germinal epithelium during their non-breeding season consisting only of Sertoli cells and SSCs. The latter re-initiate spermatogenesis prior to the next breeding-season. Fully involuted testes from a seasonal hamster and NHP (Lemur catta) exhibited numerous LIN28-positive spermatogonia, indicating a SSC-identity of the labeled cells. We conclude that LIN28 is differentially expressed in mouse and non-human primate spermatogonia and might be a marker for a rare SSC population in non-human primates and man. Further characterization of the LIN28-positive population is required. European Society of Human Reproduction and Embryology