Genetic and epigenetic properties of mouse male germline stem cells during long-term culture
Genetic and epigenetic properties of mouse male germline stem cells during long-term culture
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DOI：
10.1242/dev.02004
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发表时间：
2005-09-01
期刊：
影响因子：
4.6
通讯作者：
Shinohara, T
中科院分区：
文献类型：
--
作者：
Kanatsu-Shinohara, M;Ogonuki, N;Shinohara, T
尽管干细胞被认为可以通过自我更新分裂进行无限分裂，但很少有证据表明其无限的复制潜力。精原干细胞是精子发生的奠基细胞群。最近，精原干细胞的体外培养被描述。精原干细胞在胶质细胞源性神经营养因子（GDNF）的存在下可以在体外扩增，并在移植到睾丸后保持生精能力。在这里，我们研究了稳定性和增殖能力的精原干细胞培养细胞。精原干细胞培养超过2年，并实现了类似的10（85）倍扩增。与其他生殖细胞在体外经常获得遗传和表观遗传变化不同，精原干细胞在2年的实验期间保留了整倍体核型和雄激素发生印记，并产生正常的精子发生和可育后代。然而，精原干细胞中的端粒在培养过程中逐渐缩短，表明它们不是永生的。然而，精原干细胞显著的稳定性和增殖潜力表明，它们具有独特的机制来防止遗传和表观遗传损伤传递给后代，这些特性使它们成为生殖系修饰的有吸引力的靶点。
Although stem cells are believed to divide infinitely by self-renewal division, there is little evidence that demonstrates their infinite replicative potential. Spermatogonial stem cells are the founder cell population for spermatogenesis. Recently, in vitro culture of spermatogonial stem cells was described. Spermatogonial stem cells can be expanded in vitro in the presence of glial cell line-derived neurotrophic factor (GDNF), maintaining the capacity to produce spermatogenesis after transplantation into testis. Here, we examined the stability and proliferative capacity of spermatogonial stem cells using cultured cells. Spermatogonial stem cells were cultured over 2 years and achieved similar to 10(85)-fold expansion. Unlike other germline cells that often acquire genetic and epigenetic changes in vitro, spermatogonial stem cells retained the euploid karyotype and androgenetic imprint during the 2-year experimental period, and produced normal spermatogenesis and fertile offspring. However, the telomeres in spermatogonial stem cells gradually shortened during culture, suggesting that they are not immortal. Nevertheless, the remarkable stability and proliferative potential of spermatogonial stem cells suggest that they have a unique machinery to prevent transmission of genetic and epigenetic damages to the offspring, and these characteristics make them an attractive target for germline modification.