Pluripotency of spermatogonial stem cells from adult mouse testis
Pluripotency of spermatogonial stem cells from adult mouse testis
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DOI：
10.1038/nature04697
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发表时间：
2006-04-27
期刊：
影响因子：
64.8
通讯作者：
Hasenfuss, G
中科院分区：
文献类型：
--
作者：
Guan, K;Nayernia, K;Hasenfuss, G
胚胎生殖细胞以及来自新生小鼠睾丸的生殖系干细胞是多能的，并且具有与胚胎干细胞相似的分化潜能（1，2），这表明生殖系谱系可以保留产生多能细胞的能力。然而，到目前为止，还没有证据表明成年精原干细胞（SSC）的多能性和可塑性，这些干细胞负责维持男性一生的精子发生（3）。在这里，我们展示了使用遗传选择从成年小鼠睾丸中分离SSCs，成功率为27%。这些分离的精原干细胞对培养条件有反应并获得胚胎干细胞特性。我们将这些细胞命名为多能成体生殖系干细胞（maGSC）。它们能够在体外自发分化为三个胚胎胚层的衍生物，并在免疫缺陷小鼠中产生畸胎瘤。当注射到早期胚泡中时，SSC有助于各种器官的发育并显示生殖系传播。因此，形成多能细胞的能力在成年小鼠睾丸中持续存在。从睾丸活检建立人maGSC可以允许基于个体细胞的治疗，而没有与人胚胎干细胞相关的伦理和免疫学问题。此外，这些细胞可能为研究各种细胞谱系中的遗传疾病提供新的机会。
Embryonic germ cells as well as germline stem cells from neonatal mouse testis are pluripotent and have differentiation potential similar to embryonic stem cells(1,2), suggesting that the germline lineage may retain the ability to generate pluripotent cells. However, until now there has been no evidence for the pluripotency and plasticity of adult spermatogonial stem cells (SSCs), which are responsible for maintaining spermatogenesis throughout life in the male(3). Here we show the isolation of SSCs from adult mouse testis using genetic selection, with a success rate of 27%. These isolated SSCs respond to culture conditions and acquire embryonic stem cell properties. We name these cells multipotent adult germline stem cells (maGSCs). They are able to spontaneously differentiate into derivatives of the three embryonic germ layers in vitro and generate teratomas in immunodeficient mice. When injected into an early blastocyst, SSCs contribute to the development of various organs and show germline transmission. Thus, the capacity to form multipotent cells persists in adult mouse testis. Establishment of human maGSCs from testicular biopsies may allow individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells. Furthermore, these cells may provide new opportunities to study genetic diseases in various cell lineages.