Guan Kaomei, Nayernia Karim, Maier Lars S, Wagner Stefan, Dressel Ralf, Lee Jae Ho, Nolte Jessica, Wolf Frieder, Li Manyu, Engel Wolfgang, Hasenfuss Gerd
Department of Cardiology and Pneumology, Heart Center, Georg-August-University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Nature. 2006 Apr 27;440(7088):1199-203. doi: 10.1038/nature04697. Epub 2006 Mar 24.
Embryonic germ cells as well as germline stem cells from neonatal mouse testis are pluripotent and have differentiation potential similar to embryonic stem cells, 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. 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.
胚胎生殖细胞以及新生小鼠睾丸中的生殖系干细胞具有多能性，且具有与胚胎干细胞相似的分化潜能，这表明生殖系谱系可能保留了产生多能细胞的能力。然而，迄今为止，尚无证据表明成年精原干细胞（SSCs）具有多能性和可塑性，成年精原干细胞负责男性终生维持精子发生。在此，我们展示了利用基因筛选从成年小鼠睾丸中分离出精原干细胞，成功率为27%。这些分离出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年生殖系干细胞（maGSCs）。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形成畸胎瘤。当注入早期囊胚时，精原干细胞有助于各种器官的发育并显示种系传递。因此，成年小鼠睾丸中存在形成多能细胞的能力。从睾丸活检组织中建立人类多能成年生殖系干细胞可能允许进行基于个体细胞的治疗，而不会出现与人类胚胎干细胞相关的伦理和免疫问题。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。
