Microarray analysis of gene expression of bone marrow stem cells cocultured with salivary acinar cells.

BACKGROUND/PURPOSE:Our previous work has demonstrated that rat bone marrow stem cells (BMSCs) can transdifferentiate into α-amylase-producing cells after coculture with rat submandibular gland acinar cells. These transdifferentiated cells may be used for regeneration of damaged salivary gland. The purpose of this study was to investigate the global gene expression of rat BMSCs cocultured with rat submandibular gland acinar cells and the factors inducing this transdifferentiation. METHODS:Rat BMSCs were indirectly cocultured with rat submandibular gland acinar cells by using the double chamber system for 5 and 10 days. The global gene expression of BMSCs during transdifferentiation into acinar cells was investigated by microarray analysis. RESULTS:A total of 45,018 probes were used and 41,012 genes were detected. After coculture for 5 days, 1409 genes were upregulated more than twofold and 1417 genes were downregulated more than twofold (p<0.005). Moreover, after coculture for 10 days, 1356 genes were upregulated more than twofold and 1231 genes were downregulated more than twofold (p<0.005). Bone morphogenetic protein (BMP)-6 was one of the top-ranked upregulated genes. The hub genes were interleukin-6 and CCAAT/enhancer-binding protein β (CEBPB) in the early and late response gene groups, respectively. CONCLUSION:This is believed to be the first study on the global gene expression of rat BMSCs cocultured with rat acinar cells. Many genes related to the function of salivary acinar cells such as those responsible for the production of α-amylase protein were upregulated and many genes related to the differentiation of BMSCs into adipocytes and osteoblasts were downregulated. In addition, BMP-6 gene was found to be highly upregulated. We proposed that three target genes, BMP-6, interleukin-6 and CEBPB, play important roles in the transdifferentiation of BMSCs into acinar cells, and are worthy of further investigation.

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