Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow 143028, Russia.
Stem Cell Reports. 2017 Nov 14;9(5):1706-1720. doi: 10.1016/j.stemcr.2017.09.013. Epub 2017 Oct 26.
Naked mole rats (NMRs) are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs) from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns. Interestingly, NMR embryonic fibroblasts and the derived iPSCs had propensity for a tetraploid karyotype and were resistant to forming teratomas, but within mouse blastocysts they contributed to both interspecific placenta and fetus. Gene expression patterns of NMR iPSCs were more similar to those of human than mouse iPSCs. Overall, we uncovered unique features of NMR iPSCs and report a mouse-NMR chimeric model. The iPSCs and associated cell culture systems can be used for a variety of biological and biomedical applications.
裸鼹鼠(NMRs)是一种极其长寿、抗癌的啮齿动物。确定这些特征的定义特征可能有助于揭示衰老和癌症的机制。在这里,我们报告了从 NMR 成纤维细胞中生成诱导多能干细胞(iPSCs)及其对鼠-裸鼹鼠嵌合胚胎的贡献。在 N2B27+2i 条件下可以观察到有效的重编程。iPSCs 表现出典型的形态,表达多能标记物,形成胚状体,并表现出典型的分化模式。有趣的是,NMR 胚胎成纤维细胞和衍生的 iPSCs 具有四倍体核型的倾向,并且不易形成畸胎瘤,但在小鼠囊胚中,它们有助于同种异体胎盘和胎儿的形成。NMR iPSCs 的基因表达模式与人类 iPSCs 更相似,而不是与小鼠 iPSCs 更相似。总的来说,我们揭示了 NMR iPSCs 的独特特征,并报告了一种鼠-裸鼹鼠嵌合模型。iPSCs 和相关的细胞培养系统可用于各种生物学和生物医学应用。