Highly rapid and efficient conversion of human fibroblasts to keratinocyte-like cells.
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.
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.
Yifang
Y
Chen
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.
Devendra S
DS
Mistry
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.
George L
GL
Sen
D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D061252:Feeder Cells / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D052816:Foreskin / Q000166:cytology*; D015870:Gene Expression / Q000502:physiology; D045325:HCT116 Cells; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D000074462:Positive Regulatory Domain I-Binding Factor 1; D061251:Primary Cell Culture; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; C473143:GRHL3 protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; C490319:OVOL1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1