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Transient expression of OCT4 is sufficient to allow human keratinocytes to change their differentiation pathway

Gene Therapy volume 18, pages 294–303 (2011)Cite this article

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Abstract

In this study, we describe a simple system in which human keratinocytes can be redirected to an alternative differentiation pathway. We transiently transfected freshly isolated human skin keratinocytes with the single transcription factor OCT4. Within 2 days these cells displayed expression of endogenous embryonic genes and showed reduced genomic methylation. More importantly, these cells could be specifically converted into neuronal and contractile mesenchymal cell types. Redirected differentiation was confirmed by expression of neuronal and mesenchymal cell mRNA and protein, and through a functional assay in which the newly differentiated mesenchymal cells contracted collagen gels as efficiently as authentic myofibroblasts. Thus, to generate patient-specific cells for therapeutic purposes, it may not be necessary to completely reprogram somatic cells into induced pluripotent stem cells before altering their differentiation and grafting them into new tissues.

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Acknowledgements

We thank the members of the Bickenbach lab for helpful discussion, Matthew Fitzgerald and Dr Frederick Domann for assistance with the bisulfite technique and members of the UI Flow Cytometry Core. This research was funded in part by grants from the National Institutes of Health to JRB (R21AR053936 and R01AR053619) and by a grant from the Maryland Stem Cell Research Fund to RLE and JRB (MSCRFII-0178-01).

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  1. D Racila and M Winter: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    D Racila, M Winter, M Said, A Tomanek-Chalkley, S Wiechert & J R Bickenbach

  2. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA

    R L Eckert

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  1. D Racila
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Correspondence to J R Bickenbach.

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Racila, D., Winter, M., Said, M. et al. Transient expression of OCT4 is sufficient to allow human keratinocytes to change their differentiation pathway. Gene Ther 18, 294–303 (2011). https://doi.org/10.1038/gt.2010.148

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