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iPS cells produce viable mice through tetraploid complementation

Nature volume 461, pages 86–90 (2009)Cite this article

Abstract

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, fertile 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.

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Figure 1: Characterization of the iPS cells generated in 20% knockout serum replacement culture systems.
Figure 2: In vivo developmental potential of iPS cell lines generated by tetraploid complementation.
Figure 3: Global gene expression analysis of iPS cell lines competent for tetraploid complementation.

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Gene Expression Omnibus

Data deposits

The microarray data in this study have been deposited with the Gene Expression Omnibus repository (http://www.ncbi.nlm.nih.gov/geo) under accession number GSE16925.

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Acknowledgements

This study was supported in part by grants from the China National Basic Research Program 2006CB701500 (to Q.Z.), 2007CB947800 (to F.Z.), 2007CB947700 (to L.W.) and grants from the National Science Foundation of China 30525040 (to Q.Z.) and 30871379/C0607 (to F.Z.).

Author Contributions Q.Z. and F.Z. designed the experiments, supervised lab work, analysed and interpreted data, and wrote the paper; X.Z., W.L., Z.L., L.L., M.T., T.H., J.H., C.G., Q.M. and F.Z. performed experiments; L.L. and W.L. analysed data; W.L. supervised experiments; and X.Z., W.L. and Z.L. contributed to part of the Online Methods section.

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Author notes

  1. Xiao-yang Zhao, Wei Li and Zhuo Lv: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

    Xiao-yang Zhao, Wei Li, Zhuo Lv, Lei Liu, Man Tong, Tang Hai, Jie Hao, Chang-long Guo, Liu Wang & Qi Zhou

  2. Graduate School of Chinese Academy of Sciences, Beijing 100049, China

    Xiao-yang Zhao, Wei Li, Zhuo Lv, Man Tong, Jie Hao & Chang-long Guo

  3. Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China

    Qing-wen Ma & Fanyi Zeng

  4. Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

    Fanyi Zeng

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  1. Xiao-yang Zhao
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Correspondence to Fanyi Zeng or Qi Zhou.

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Zhao, Xy., Li, W., Lv, Z. et al. iPS cells produce viable mice through tetraploid complementation. Nature 461, 86–90 (2009). https://doi.org/10.1038/nature08267

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