Homing efficiency and proliferation kinetics of male germ line stem cells following transplantation in mice.
Stem cells in the male germ line (spermatogonial stem cells [SSCs]) are an important target for male fertility restoration and germ line gene modification. To establish a model system to study the biology and the applications of SSCs in mice, I used a sequential transplantation strategy to analyze the process by which SSCs colonize the stem cell niche after transplantation and to determine the efficiency of the process (homing efficiency). I further analyzed the proliferation kinetics of SSCs after colonization. The number of SSCs gradually decreased during the homing process, and only 12% of SSCs successfully colonized the niche on Day 7 after transplantation, but the number of SSCs increased by Day 14. Thus, homing efficiency of adult mouse SSCs is 12%. These results indicate that SSCs are rapidly lost upon transplantation and require approximately 1 wk to settle into their niches before initiating expansion. Using this SSC homing efficiency, I calculated that approximately 3000 SSCs exist in one normal adult testis, representing approximately 0.01% of total testis cells. Between 7 days and 1 mo after transplantation, SSCs proliferated 7.5-fold. However, they did not significantly proliferate thereafter until 2 mo, and only 8 SSCs supported one colony of donor-derived spermatogenesis from 1 to 2 mo. These results suggest that self-renewal and differentiation of SSCs are strictly regulated in coordination with the progress of an entire unit of regenerating spermatogenesis.
Nagano
Makoto C
MC
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada H3A 1A1. makoto.nagano@muhc.mcgill.ca
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement; D005854:Germ Cells / Q000502:physiology* / Q000637:transplantation; D007700:Kinetics; D008297:Male; D051379:Mice; D013093:Spermatogonia / Q000502:physiology; D033581:Stem Cell Transplantation; D013737:Testis / Q000166:cytology