Comparative gene expression profiling reveals key pathways and genes different in skin epidermal stem cells and corneal epithelial cells.

Abstract

Corneal epithelial cells (CECs) are required for corneal transparency and visual function, and corneal injuries may cause corneal blindness. Skin epidermal stem cells (SESCs), which share the same origin with CECs and have the potential of multi-directional differentiation are ideal seed cells for tissue engineered corneal construction to treat corneal blindness. This study aims to investigate critical genes and pathways that may modulate the transdifferentiation from SESCs to CECs. Isolated SESCs and CECs were used for gene expression analysis by microarray. GO and KEGG pathway of differently expressed genes (DEGs) were enriched using DAVID. The protein-protein interaction (PPI) network were then constructed using Cytoscape and highly interconnected module was subsequently isolated from the network by Molecular Complex Detection. Expression of the hub genes and other selected genes were then verified by qRT-PCR. We found 112 upregulated and 105 downregulated genes in CECs compared with SESCs. These DEGs were significantly enriched in focal adhesion, PI3K-Akt and TNF signaling pathway. Highly interconnected module of PPI network contains ten genes. Further regulatory network of these genes showed that ESR1 and SLC2A4 were hub genes. Our study identified gene expression in SESCs and CECs and suggested that several crucial genes and pathways may play critical roles in transdifferentiation from SESCs to CECs. It may help uncover molecular mechanisms and offer a foundation for promoting tissue-engineered cornea into clinical application.