State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Key Laboratory of Translational Stem Cell Research, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Translational Stem Cell Research, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
J Biol Chem. 2013 Sep 20;288(38):27150-27158. doi: 10.1074/jbc.M113.492900. Epub 2013 Aug 7.
The rat is an important animal model for human disease research. Using inhibitors of glycogen synthase kinase 3 and MAPK signaling pathways, rat embryonic stem cells and rat induced pluripotent stem cells (riPSCs) have been derived. However, unlike rat embryonic stem cells, germ line competent riPSCs have only been derived from Wistar rats at low efficiency. Here, we found that an optimized induction medium containing knock-out serum replacement and vitamin C improved the rate and efficiency of riPSCs generation from Dark Agouti rat fibroblasts and Sertoli cells. riPSCs maintained an undifferentiated status for >30 passages and could differentiate into various cells types including germ cells when injected into rat blastocysts. Moreover, transgenic riPSCs could be generated through the PiggyBac transposon, which could be used to generate transgenic rats through germ line transmission. riPSCs can be used as a novel tool in genetic and genomic studies of the rat.
大鼠是研究人类疾病的重要动物模型。使用糖原合酶激酶 3 和 MAPK 信号通路的抑制剂，已经从大鼠胚胎干细胞和大鼠诱导多能干细胞（riPSC）中得到。然而，与大鼠胚胎干细胞不同的是，种系相容的 riPSC 仅从 Wistar 大鼠中以低效率获得。在这里，我们发现，含有无血清替代物和维生素 C 的优化诱导培养基可提高 Dark Agouti 大鼠成纤维细胞和 Sertoli 细胞生成 riPSC 的效率和速度。riPSC 保持未分化状态超过 30 代，并且当注入大鼠囊胚时可以分化为各种细胞类型，包括生殖细胞。此外，通过 PiggyBac 转座子可以产生转基因 riPSC，通过种系传递可以用于产生转基因大鼠。riPSC 可作为大鼠遗传和基因组研究的新工具。
