Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4
Name
Lyssiotis-2009-Reprogramming of mur.pdf
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Author(s)
Hanna, Jacob
Markoulaki, Styliani
Mathur, Divya
Staerk, Judith
Foreman, Ruth K.
Jaenisch, Rudolf
Schultz, Peter G.
Cho, Charles Y.
Brinker, Achim
Kunick, Conrad
Date Issued
April 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
United States National Academy of Sciences
Citation
Lyssiotis, Costas A et al. “Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4.” Proceedings of the National Academy of Sciences 106.22 (2009): 8912-8917. © 2009 National Academy of Sciences
Version
Final published version
Abstract
Ectopic expression of defined transcription factors can reprogram somatic cells to induced pluripotent stem (iPS) cells, but the utility of iPS cells is hampered by the use of viral delivery systems. Small molecules offer an alternative to replace virally transduced transcription factors with chemical signaling cues responsible for reprogramming. In this report we describe a small-molecule screening platform applied to identify compounds that functionally replace the reprogramming factor Klf4. A series of small-molecule scaffolds were identified that activate Nanog expression in mouse fibroblasts transduced with a subset of reprogramming factors lacking Klf4. Application of one such molecule, kenpaullone, in lieu of Klf4 gave rise to iPS cells that are indistinguishable from murine embryonic stem cells. This experimental platform can be used to screen large chemical libraries in search of novel compounds to replace the reprogramming factors that induce pluripotency. Ultimately, such compounds may provide mechanistic insight into the reprogramming process.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1073/pnas.0903860106
