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A chemical platform for improved induction of human iPSCs

Abstract

The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (200-fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, nonviral methods for reprogramming human somatic cells.

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Figure 1: Compound treatment for 7 d is sufficient to induce pluripotent stem cells from human fibroblasts transduced with the four reprogramming factors.
Figure 2: Prolonged compound treatment and cell passaging dramatically increased the number of reprogrammed colonies.
Figure 3: In vitro and in vivo differentiation of iPSCs generated with three-compound treatment.

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Acknowledgements

This work was supported by funding from US National Institutes of Health and Fate Therapeutics to S.D. We thank C.V. Wright (Vanderbilt University medical center) for the gift of Pdx1 antibody, R. Coleman for the assistance in the preparation of the manuscript and all the members of Ding lab for helpful discussions.

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Authors and Affiliations

Authors

Contributions

T.L. and S.D. initiated the study. S.D., R. Am. and T.L. made the hypothesis, designed the experiments and wrote the manuscript. T.L., R. An, X.Y., H.S.H., and W.L. conducted the experiments. S.H., R. Ab. and X.L. provided assistance in some of the experiments. E.H. generated teratomas, and A.H. supervised E.H. S.D. supervised the study.

Corresponding author

Correspondence to Sheng Ding.

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Supplementary Figures 1–4 and Supplementary Table 1 (PDF 732 kb)

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Lin, T., Ambasudhan, R., Yuan, X. et al. A chemical platform for improved induction of human iPSCs. Nat Methods 6, 805–808 (2009). https://doi.org/10.1038/nmeth.1393

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