Serial analysis of gene expression in differentiated cultures of human epidermal keratinocytes

Keratinocyte gene expression was surveyed more comprehensively than before, by means of serial analysis of gene expression. A total of 25,694 tags der ived from expressed mRNA, were analyzed in a model for normal differentiati on and in a model where cultured keratinocytes were stimulated for a prolon ged period of time with tumor necrosis factor-alpha, thus mimicking aberran t differentiation in the context of cutaneous inflammation. Serial analysis of gene expression revealed many transcripts derived from unknown genes an d a large number of genes that are not known to be expressed in keratinocyt es; furthermore, these data provide quantitative information about the rela tive abundance of transcripts, allowing the identification of differentiall y expressed genes. A major part of the identified transcripts accounted for genes involved in energy metabolism and protein synthesis. A large proport ion of all transcripts (6%) corresponded to genes associated with terminal differentiation and barrier formation. Another highly expressed functional group of genes (2% of all transcripts) corresponded to proteins involved in host protection such a antimicrobial proteins and proteinase inhibitors. T hree of these genes were not known to be expressed in keratinocytes, and so me were upregulated after prolonged tumor necrosis factor-alpha exposure. O ur data on expressed genes in keratinocytes are consistent with the known f unction of human epidermis, and provide a first step to generate a transcri ptome of human keratinocytes.