Tsukuba Primate Research Center (TPRC), National Institute of Biomedical Innovation (NIBIO), 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan.
Differentiation. 2013 Apr-Jun;85(4-5):131-9. doi: 10.1016/j.diff.2013.02.004. Epub 2013 Jun 19.
Induced pluripotent stem (iPS) cells established by introduction of the transgenes POU5F1 (also known as Oct3/4), SOX2, KLF4 and c-MYC have competence similar to embryonic stem (ES) cells. iPS cells generated from cynomolgus monkey somatic cells by using genes taken from the same species would be a particularly important resource, since various biomedical investigations, including studies on the safety and efficacy of drugs, medical technology development, and research resource development, have been performed using cynomolgus monkeys. In addition, the use of xenogeneic genes would cause complicating matters such as immune responses when they are expressed. In this study, therefore, we established iPS cells by infecting cells from the fetal liver and newborn skin with amphotropic retroviral vectors containing cDNAs for the cynomolgus monkey genes of POU5F1, SOX2, KLF4 and c-MYC. Flat colonies consisting of cells with large nuclei, similar to those in other primate ES cell lines, appeared and were stably maintained. These cell lines had normal chromosome numbers, expressed pluripotency markers and formed teratomas. We thus generated cynomolgus monkey iPS cell lines without the introduction of ecotropic retroviral receptors or other additional transgenes by using the four allogeneic transgenes. This may enable detailed analysis of the mechanisms underlying the reprogramming. In conclusion, we showed that iPS cells could be derived from cynomolgus monkey somatic cells. To the best of our knowledge, this is the first report on iPS cell lines established from cynomolgus monkey somatic cells by using genes from the same species.
诱导多能干细胞（iPS）通过引入多能性转录因子 POU5F1（也称为 Oct3/4）、SOX2、KLF4 和 c-MYC 等基因而建立，其具有与胚胎干细胞（ES）相似的全能性。使用来自同一物种的基因从食蟹猴体细胞中产生 iPS 细胞将是一个特别重要的资源，因为已经使用食蟹猴进行了各种生物医学研究，包括药物安全性和有效性研究、医疗技术开发和研究资源开发。此外，当表达异种基因时，会引起免疫反应等复杂问题。因此，在这项研究中，我们通过用含有食蟹猴 POU5F1、SOX2、KLF4 和 c-MYC 基因的 cDNA 的双嗜性逆转录病毒载体感染胎肝和新生皮肤细胞，建立了 iPS 细胞。出现了类似于其他灵长类 ES 细胞系的具有大核的扁平细胞集落，并稳定维持。这些细胞系具有正常的染色体数目，表达多能性标记物，并形成畸胎瘤。因此，我们在不引入ecotropic 逆转录病毒受体或其他额外转基因的情况下，使用这四个同种异体转基因成功生成了食蟹猴 iPS 细胞系。这可能使我们能够详细分析重编程的机制。总之，我们表明可以从食蟹猴体细胞中获得 iPS 细胞。据我们所知，这是首次使用来自同一物种的基因从食蟹猴体细胞中建立 iPS 细胞系的报告。
