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J Invest Dermatol. 2014 Feb;134(2):335-344. doi: 10.1038/jid.2013.327. Epub 2013 Aug 6.

Highly rapid and efficient conversion of human fibroblasts to keratinocyte-like cells.

Author information

1
Division of Dermatology, Department of Medicine, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, California, USA.
2
Division of Dermatology, Department of Medicine, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, California, USA. Electronic address: gsen@ucsd.edu.

Abstract

Cell fate commitment during development is achieved through the expression of lineage-specific transcription factors. Recent studies have suggested that the expression of combinations of these lineage-specific transcription factors can convert adult somatic cells from one type to another. Here we report that the combination of p63, a master regulator of epidermal development and differentiation, and KLF4, a regulator of epidermal differentiation, is sufficient to convert dermal fibroblasts to a keratinocyte phenotype. Induced keratinocytes (KCs) expressed KC-specific proteins and had a transcriptome similar to KCs. Reprogramming to a KC phenotype was rapid and efficient with a vast majority of cells morphologically resembling and expressing KC-specific genes within a week of p63 and KLF4 transduction. Furthermore, p63 and KLF4 are capable of inducing a KC phenotype even in a cancerous cell line, highlighting their importance for epidermal specification. The robustness of the conversion process also allows the use of this as a model system to study the mechanisms of reprogramming.

PMID:
23921950
PMCID:
PMC3875612
DOI:
10.1038/jid.2013.327
[Indexed for MEDLINE]
Free PMC Article

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