Homing efficiency and proliferation kinetics of male germ line stem cells following transplantation in mice
Homing efficiency and proliferation kinetics of male germ line stem cells following transplantation in mice
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DOI：
10.1095/biolreprod.103.016352
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发表时间：
2003-08-01
影响因子：
3.6
通讯作者：
Nagano, MC
中科院分区：
文献类型：
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作者：
Nagano, MC
精子干细胞（spermatogial Stem cells, SSCs）是男性生殖功能恢复和生殖系基因修饰的重要靶点。为了建立一个模型系统来研究SSCs在小鼠体内的生物学和应用，我采用顺序移植策略来分析移植后SSCs在干细胞生态位上定植的过程，并确定该过程的效率（归巢效率）。我进一步分析了SSCs定殖后的增殖动力学。在归巢过程中，SSCs的数量逐渐减少，移植后第7天，只有12%的SSCs成功定殖，但到第14天，SSCs的数量增加。因此，成年小鼠ssc的归巢效率为12%。这些结果表明，ssc在移植后迅速丢失，并且在开始扩增之前需要大约1周的时间来适应它们的生态位。利用这种SSC归巢效率，我计算出一个正常成年睾丸中存在大约3000个SSC，约占睾丸细胞总数的0.01%。移植后7天至1个月，ssc增殖7.5倍。然而，直到2个月后，它们才开始显著增殖，从1到2个月，只有8个ssc支持一个供体来源的精子发生。这些结果表明，ssc的自我更新和分化受到严格的调节，与整个再生精子发生单位的进展相协调。
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 similar to1 wk to settle into their niches before initiating expansion. Using this SSC homing efficiency, I calculated that similar to3000 SSCs exist in one normal adult testis, representing similar to0.01% of total testis cells. Between 7 days and I 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.