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iPS cells produce viable mice through tetraploid complementationnear-final version
Xiao-yang Zhao1,2,5, Wei Li1,2,5, Zhuo Lv1,2,5, Lei Liu1, Man Tong1,2, Tang Hai1, Jie Hao1,2, Chang-long Guo1,2, Qing-wen Ma3, Liu Wang1, Fanyi Zeng3,4 & Qi Zhou1
1 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2 Graduate School of Chinese Academy of Sciences, Beijing 100049, China
3 Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China
4 Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
5 These authors contributed equally to this work.
6 Correspondence to: Fanyi Zeng3,4Qi Zhou1 Correspondence and requests for materials should be addressed to Q.Z.
Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat1, 2, 3, 4, 5, 6. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells7, 8. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.
