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PAX7 expression defines germline stem cells in the adult testis
Gina M. Aloisio, … , F. Kent Hamra, Diego H. Castrillon
Gina M. Aloisio, … , F. Kent Hamra, Diego H. Castrillon
Published August 18, 2014
Citation Information: J Clin Invest. 2014;124(9):3929-3944. https://doi.org/10.1172/JCI75943.
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Research Article Article has an altmetric score of 42

PAX7 expression defines germline stem cells in the adult testis

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Abstract

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.

Authors

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

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Figure 6

PAX7+ spermatogonia have long-term stem potential in vivo, and their descendants function as stem cells in transplantation assays.

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PAX7+ spermatogonia have long-term stem potential in vivo, and their des...
For PD3 time points, tamoxifen injections were performed at PD1 and PD2; for later time points, tamoxifen administration was performed for 3 consecutive days starting at PD3. (A) Clone size. Each column represents 1 testis from separate animals (total n = 15); red bars denote means. Note that many labeled Asingle spermatogonia were present at PD21, demonstrating that PD21 PAX7+ spermatogonia are derived from neonatal PAX7+ spermatogonia. Clones grew over time and persisted in aged animals (12 weeks). (B) Representative clone morphologies by confocal microscopy (n denotes number of cells in labeled chain shown); z stacks confirmed cell counts and Asingle status. (C) Mitotic and apoptotic indices of PAX7+ cells at PD3 (n = 3 animals) demonstrated that early PAX7+ cells were highly proliferative and not characterized by significant apoptosis. Error bars denote SEM. (D) Transplantation assay. A Pax7-CreERT2;tdTomato donor was treated with tamoxifen at PD3. Testes were disaggregated at PD14 and transplanted into germ cell–deficient KitW/KitW–v hosts, which were sacrificed after 4 weeks (n = 3). All hosts (but no controls) showed multiple labeled clones (i.e., 15–20); representative examples are shown. Scale bars: 25 μm (B); 100 μm (D).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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