GERMLINE TRANSMISSION OF DONOR HAPLOTYPE FOLLOWING SPERMATOGONIAL TRANSPLANTATION
GERMLINE TRANSMISSION OF DONOR HAPLOTYPE FOLLOWING SPERMATOGONIAL TRANSPLANTATION
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DOI：
10.1073/pnas.91.24.11303
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发表时间：
1994-11-22
影响因子：
11.1
通讯作者：
AVARBOCK, MR
中科院分区：
文献类型：
--
作者：
BRINSTER, RL;AVARBOCK, MR
精子发生是一个复杂、高度组织化、非常有效的过程，其基础是干细胞精原细胞同时进行自我更新并提供分化为成熟精子的后代的能力。我们在此报告，睾丸来源的细胞移植到不育小鼠的睾丸中，将定植于生精小管，并在> 70%的受体中启动精子发生。来自新生小鼠的睾丸来源的细胞在移植受体睾丸中的效果不如来自5至15或21至28天龄小鼠的细胞。增加供体细胞群中支持细胞的数量并没有增加定殖的效率。未经修饰的胚胎干细胞不能替代睾丸来源的细胞，而是在同基因和非同基因宿主中形成肿瘤。最后，对于维持内源性精子发生的受体，睾丸细胞移植产生的小鼠中高达80%的后代是由供体来源的精子产生的。随着精原细胞培养技术的发展，精原细胞移植技术应能在多种物种中产生生殖细胞修饰，并在生物学、医学和农业方面有更多的应用。
Spermatogenesis is a complex, highly organized, very efficient process that is based upon the capacity of stem cell spermatogonia simultaneously to undergo self-renewal and to provide progeny that differentiate into mature spermatozoa. We report here that testis-derived cells transplanted into the testis of an infertile mouse will colonize seminiferous tubules and initiate spermatogenesis in > 70% of recipients. Testis-derived cells from newborn mice were less effective in colonizing recipient testes than cells from 5- to 15- or 21- to 28-day-old mice. Increasing the number of Sertoli cells in the donor cell population did not increase the efficiency of colonization. Unmodified embryonic stem cells were not able to substitute for testis-derived cells in colonizing testes but instead formed tumors in syngeneic as well as nonsyngeneic hosts. Finally, with recipients that maintained endogenous spermatogenesis, testis cell transplantation yielded mice in which up to 80% of progeny were sired by donor-derived spermatozoa. The technique of spermatogonial cell transplantation should pro vide a means to generate germline modifications in a variety of species following development of spermatogonial culture techniques and should have additional applications in biology, medicine, and agriculture.