Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model

The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFβ1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes.Our results reveal potential new signaling pathways and several new genes affected by TGFβ in epithelial cell differentiation. The differentiation induced by TGFβ1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells.The intestinal epithelium comprises multiple cell types which are progenitors of the stem cells located in crypt region. During their migration along the crypt axis epithelial cells differentiate from proliferative cells into secretory cells or absorptive enterocytes [1] Epithelial cell growth, motility and morphogenesis are controlled by soluble factors such as transforming growth factor beta (TGFβ) [1], a multifunctional growth factor [2-4]. Mesenchymal cells producing TGFβ are in turn regulated by various hormonal, paracrine and exogenous factors [5,6]. Epithelial cells can also regulate their own gene expression via negative regulatory feedback loops [7]. The role of the specific signaling pathways across the crypt axis, and the transcription factors controlling the crypt-specific expression of specific g