Identification of potential effectors in Sjögren’s syndrome using epithelial progenitor cells of the salivary gland
Patel, Trusha Nitin
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Sjögren’s syndrome (SS) is an autoimmune disease that affects predominantly the salivary glands and lacrimal glands, leading to dry mouth and dry eyes. Although significant effort targeting the activated immune cells in SS has been made, there is still no cure for SS. These observations implicate that immune cell may not be the unique source of the cells that drive the pathogenesis of SS. Recently, Senoo lab has made a novel observation that mice conditionally expressing the transcription factor p63 in progenitor cells of the salivary gland epithelia develop SS-like autoimmune disease. In this study, we investigated whether epithelial progenitor cells of the salivary glands in patients with SS express higher levels of p63 than those in non-disease controls. Our data show that expression of p63 in ductal epithelia of labial salivary glands in patients with SS was significantly higher than that of non-disease controls. Subsequently, we aimed at identifying the potential effectors that drive the pathogenesis of SS by comparing the gene expression profile of the p63-positive salivary gland epithelial progenitor cells of patients with SS and of non-disease controls. To address this issue, we employed novel culture of epithelial stem/progenitor cells we have established recently and used deep-RNA sequencing followed by verification of differential gene expression using quantitative PCR (q-PCR). Further, we cross-referenced our dataset with known SS-associated genes in literature and narrowed down to the top 11 candidate genes. Future studies should focus on the functional analysis of each p63-assocciated candidate gene in the pathogenesis of SS.