Highly Rapid and Efficient Conversion of Human Fibroblasts to Keratinocyte-Like Cells

Abstract

Cell fate commitment during development is achieved through the expression of lineage specific transcription factors. Recent studies have suggested that 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 expressed keratinocyte specific proteins and had a transcriptome similar to keratinocytes. Reprogramming to a keratinocyte phenotype was rapid and efficient with a vast majority of cells morphologically resembling and expressing keratinocyte specific genes within a week of p63 and KLF4 transduction. Furthermore, p63 and KLF4 are capable of inducing a keratinocyte 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.