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Transient folate deprivation in combination with small-molecule compounds facilitates the generation of somatic cell-derived pluripotent stem cells in mice

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Summary

Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical research. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel approach to generating iPSCs. In this study, a new combination of small-molecule compounds (SMs) (sodium butyrate, A-83-01, CHIR99021, Y-27632) under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts (MEFs) in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs. The resulting cell lines resembled mouse embryonic stem (ES) cells with respect to proliferation rate, morphology, pluripotency-associated markers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcinogenicity and the use of exogenous reprogramming factors.

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Authors and Affiliations

  1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Wen-tao Hu  (胡文涛), Yu Fang  (方 瑜), Zhan-dong qiu  (邱占东) & Su-ming Zhang  (张苏明)

  2. Department of Neurology, Cangzhou Central Hospital, Cangzhou, 061000, China

    Qiu-yue Yan  (闫秋月)

Authors
  1. Wen-tao Hu  (胡文涛)
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  2. Qiu-yue Yan  (闫秋月)
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  3. Yu Fang  (方 瑜)
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  4. Zhan-dong qiu  (邱占东)
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  5. Su-ming Zhang  (张苏明)
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Corresponding author

Correspondence to Su-ming Zhang  (张苏明).

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81271407), and the Chinese Postdoctoral Scientific Research Fund (No. 20110490453).

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Hu, Wt., Yan, Qy., Fang, Y. et al. Transient folate deprivation in combination with small-molecule compounds facilitates the generation of somatic cell-derived pluripotent stem cells in mice. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 151–156 (2014). https://doi.org/10.1007/s11596-014-1249-5

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  • DOI: https://doi.org/10.1007/s11596-014-1249-5

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