The production of spermatozoa is a complex, multi-step process that allows male fertility to be maintained throughout adulthood. Continued spermatogenesis requires the presence of a population of germline stem cells known as Asingle spermatogonia. Because these cells are rare and there are no reliable markers for this population, they have been challenging to isolate and study. Using murine models, Gina Aloisio and colleagues demonstrated that Asingle spermatogonia are a heterogeneous cell population, of which a subset serves as the stem-like progenitors that initiate spermatogenesis. Lineage tracing revealed that PAX7, a known marker of satellite stem cells in skeletal muscle, specifically marks spermatogonial stem cells in the testes of adult mice. This population was present in the testes at birth, and in adult testes these rare cells gave rise to spermatozoa-producing clones. Compared to other germ line cells, PAX7+ spermatogonia in the testes survived and expanded after chemotherapy and radiotherapy, facilitating the restoration of spermatogenesis in these animals. Moreover, PAX7+ spermatogonia were present in the testes of variety of mammals, including humans. These results indicate that PAX7 is a reliable marker for stem-like Asingle spermatogonia. The accompanying image shows a cross section of the testes of an adult mouse stained for the germ cell marker KIT (red) and PAX7 (green).
Spermatogenesis is a complex, multistep process that maintains male fertility and is sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity of the spermatogonial stem cell population in the undisturbed testis is controversial due to a lack of reliable and specific markers. Here we identified the transcription factor PAX7 as a specific marker of a rare subpopulation of Asingle spermatogonia in mice. PAX7+ cells were present in the testis at birth. Compared with the adult testis, PAX7+ cells constituted a much higher percentage of neonatal germ cells. Lineage tracing in healthy adult mice revealed that PAX7+ spermatogonia self-maintained and produced expanding clones that gave rise to mature spermatozoa. Interestingly, in mice subjected to chemotherapy and radiotherapy, both of which damage the vast majority of germ cells and can result in sterility, PAX7+ spermatogonia selectively survived, and their subsequent expansion contributed to the recovery of spermatogenesis. Finally, PAX7+ spermatogonia were present in the testes of a diverse set of mammals. Our data indicate that the PAX7+ subset of Asingle spermatogonia functions as robust testis stem cells that maintain fertility in normal spermatogenesis in healthy mice and mediate recovery after severe germline injury, such as occurs after cancer therapy.
Gina M. Aloisio, Yuji Nakada, Hatice D. Saatcioglu, Christopher G. Peña, Michael D. Baker, Edward D. Tarnawa, Jishnu Mukherjee, Hema Manjunath, Abhijit Bugde, Anita L. Sengupta, James F. Amatruda, Ileana Cuevas, F. Kent Hamra, Diego H. Castrillon