Comparative Transcriptomics Reveals a Dual Role of the Epidermal Differentiation Complex in the Skin and the Oesophagus.

The epidermal differentiation complex (EDC) is a cluster of genes implicated in the control of the skin barrier. However, some EDC genes are also expressed at high levels in the human oesophagus. To determine whether the expression of EDC genes in the oesophagus is evolutionarily conserved, we performed comparative transcriptomic analyses of the skin and the oesophagus in humans, mice and chickens. Transcriptomes from public databases and newly generated RNA-sequencing data of the chicken oesophagus were compared. We found that the EDC of both mammals and birds contains genes that are predominantly expressed in the skin and others that are predominantly expressed in the oesophagus. Cornulin is strongly enriched in the oesophagus of humans and chickens. Similar to small proline-rich proteins in the human and murine oesophagus, an EDC protein rich in proline is predominantly expressed in the chicken oesophagus. Further oesophagus-enriched EDC genes are specific to phylogenetic lineages. This study indicates that the EDC plays evolutionarily ancient roles not only in the epidermis of the skin but also in the epithelium of the oesophagus. In line with the dual function of the EDC, dysregulation of EDC gene expression is associated with pathological changes in both stratified epithelia.