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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • Cell Transformation, Neoplastic / genetics
  • DNA-Binding Proteins / genetics
  • Feeder Cells / physiology
  • Fibroblasts / cytology*
  • Fibroblasts / physiology
  • Foreskin / cytology*
  • Gene Expression / physiology
  • HCT116 Cells
  • Humans
  • Infant, Newborn
  • Keratinocytes / cytology*
  • Keratinocytes / physiology
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Phenotype
  • Positive Regulatory Domain I-Binding Factor 1
  • Primary Cell Culture
  • Repressor Proteins / genetics
  • Transcription Factors / genetics

Substances

  • CKAP4 protein, human
  • DNA-Binding Proteins
  • GRHL3 protein, human
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Membrane Proteins
  • OVOL1 protein, human
  • Repressor Proteins
  • Transcription Factors
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1