骨髓基质细胞与唾液腺细胞共培养的基因表达的基因芯片分析。
Microarray analysis of gene expression of bone marrow stem cells cocultured with salivary acinar cells.
机构信息
Dentistry Department, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan, ROC; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan, ROC.
出版信息
J Formos Med Assoc. 2013 Nov;112(11):713-20. doi: 10.1016/j.jfma.2012.08.006. Epub 2012 Sep 4.
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.
背景/目的：我们之前的工作表明，大鼠骨髓间充质干细胞（BMSCs）在与大鼠颌下腺腺泡细胞共培养后可以转分化为产生α-淀粉酶的细胞。这些转分化的细胞可能用于受损唾液腺的再生。本研究的目的是探讨大鼠 BMSCs 与大鼠颌下腺腺泡细胞共培养后其整体基因表达情况，以及诱导这种转分化的因素。
方法
采用双室系统间接共培养大鼠 BMSCs 与大鼠颌下腺腺泡细胞 5 天和 10 天，通过微阵列分析研究 BMSCs 在向腺泡细胞转分化过程中的整体基因表达。
结果
使用了 45018 个探针，检测到 41012 个基因。共培养 5 天后，有 1409 个基因上调超过 2 倍，1417 个基因下调超过 2 倍（p<0.005）。此外，共培养 10 天后，有 1356 个基因上调超过 2 倍，1231 个基因下调超过 2 倍（p<0.005）。骨形成蛋白 6（BMP-6）是上调最明显的基因之一。在早期和晚期反应基因组中，枢纽基因分别为白细胞介素 6 和 CCAAT/增强子结合蛋白β（CEBPB）。
结论
这被认为是首例关于大鼠 BMSCs 与大鼠腺泡细胞共培养后的整体基因表达研究。许多与唾液腺腺泡细胞功能相关的基因（如负责产生α-淀粉酶蛋白的基因）上调，许多与 BMSCs 向脂肪细胞和成骨细胞分化相关的基因下调。此外，发现 BMP-6 基因高度上调。我们提出，三个靶基因 BMP-6、白细胞介素 6 和 CEBPB 在 BMSCs 向腺泡细胞的转分化中发挥重要作用，值得进一步研究。
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