Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Cell Transplant. 2011;20(2):193-203. doi: 10.3727/096368910X514305. Epub 2010 Aug 17.
It is possible to generate induced pluripotent stem (iPS) cells from mouse and human somatic cells by ectopic expression of defined sets of transcription factors. However, the recommendation that somatic cells should be utilized at early passages for induced reprogramming limits their therapeutic application. Here we report successful reprogramming of human fibroblasts after more than 20 passages in vitro, to a pluripotent state with four transcription factors: Oct4, Sox2, Klf4, and c-Myc. The late passage-derived human iPS cells resemble human embryonic stem cells in morphology, cell surface antigens, pluripotent gene expression profiles, and epigenetic states. Moreover, these iPS cells differentiate into cell types representative of the three germ layers in teratomas in vivo, and directed neuronal differentiation in vitro.
通过异位表达定义的转录因子组合，可以从鼠和人体细胞中生成诱导多能干细胞（iPS 细胞）。然而，建议体细胞应在早期传代时用于诱导重编程，这限制了它们的治疗应用。在此，我们报告了在体外传代 20 代以上后，利用四种转录因子（Oct4、Sox2、Klf4 和 c-Myc）成功将人成纤维细胞重编程为多能状态。晚期传代的人 iPS 细胞在形态、细胞表面抗原、多能基因表达谱和表观遗传状态上与人类胚胎干细胞相似。此外，这些 iPS 细胞在体内畸胎瘤中分化为三个胚层的代表性细胞类型，并在体外进行定向神经元分化。
