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Transgenic mice with defined combinations of drug-inducible reprogramming factors

Abstract

Proviruses carrying drug-inducible Oct4, Sox2, Klf4 and c-Myc used to derive 'primary' induced pluripotent stem (iPS) cells were segregated through germline transmission, generating mice and cells carrying subsets of the reprogramming factors. Drug treatment produced 'secondary' iPS cells only when the missing factor was introduced. This approach creates a defined system for studying reprogramming mechanisms and allows screening of genetically homogeneous cells for compounds that can replace any transcription factor required for iPS cell derivation.

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Figure 1: 'Reprogrammable' mice carrying single copies of reprogramming factors.
Figure 2: Library of MEF lines carrying different combinations of reprogramming factors.

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Acknowledgements

We thank G. Bell, R. Flannery and members of the Jaenisch lab for assistance and comments. R.J. is supported by grants from the National Institutes of Health: 5-RO1-HDO45022, 5-R37-CA084198 and 5-RO1-CA087869. J.H. is a Novartis Fellow by the Helen Hay Whitney Foundation.

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Correspondence to Rudolf Jaenisch.

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R.J. is an advisor to Stemgent.

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Supplementary Methods, Figures 1–9, Tables 1–3 (PDF 764 kb)

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Markoulaki, S., Hanna, J., Beard, C. et al. Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27, 169–171 (2009). https://doi.org/10.1038/nbt.1520

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  • DOI: https://doi.org/10.1038/nbt.1520

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