Expression Programs of Intestinal Cell Differentiation

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DESCRIPTION (provided by applicant): Intestinal epithelial cells undergo rapid and continuous cell renewal through out life. This self-renewal is maintained by a group of multipotent stem cells located at intestinal crypts. These stem cells give rise to progenitor cells, which then differentiate into different cell lineages and migrate up along the intestinal villi. Molecular genetics of this differentiation process is still poorly defined. Intestinal stem cells provide promising treatment strategy for some GI diseases, for example, inflammatory bowel disease and gut failure. However, little is known of specific markers for these stem cells, which make the isolation and culture of the stem cells difficult in vitro. We hypothesize that there are distinct gene expression programs that are associated with the developmental program of the intestine, i.e., different regions of the intestinal villi have different expression profiles. We further hypothesize that the stem cells located in the crypt side of the intestine share similar "sternness" genes with human embryonic stem cells. In this application, we propose the following aims: Aim 1: To obtain a gene expression profile of different regions of intestinal villi; Aim 2: To identify genes that are associated with different regions of intestinal epithelium, as well as genes that may be related to the intestinal stem cells; and Aim 3: To validate the expression and study the cellular localization of candidate genes. In summary, the proposed exploratory study of gene expression patterns associated with intestinal epithelial cells will provide a comprehensive picture of the differentiation program of these cells. Moreover, the genes that may be associated with intestinal stem cells will provide markers for identification, purification and characterization of these cells.