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Transcriptome Sequencing Revealed Candidate Genes Relevant to Mesenchymal Stem Cells' Role in Aortic Dissection Patients

Molecular Medicine Reports(2017)

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摘要
Aortic dissection (AD) results from the imbalance between synthesis and degradation of extracellular matrices in aortic wall, which is characterized by chronic inflammation. Mesenchymal stem cells (MSCs) are known for anti-inflammatory and repairing effects and have therefore been studied for treatment for numerous diseases, including AD. However, it is unclear which genes or signaling pathways contribute to MSCs' role in AD. In the present study, RNA sequencing (RNA-seq) was conducted between MSCs from patients with AS (AD-MSCs) and those from age-matched healthy donors (HD-MSCs). RNA-seq revealed 201 differentially expressed genes (DEGs) under the filter of fold change>2 and P-value <0.05, in which 93 genes were upregulated and 108 downregulated. We selectively verified 9 out of 201 DEGs via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with an enlarged sample size. The trends of RT-qPCR results were consistent with RNA-seq data. Unsupervised hierarchical clustering of the 9-gene expression profiles enables the division of clinical samples into AD and HD groups. Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant change in adhesion-related signaling pathways in AD-MSCs compared with HD-MSCs, whereas gene ontology analysis demonstrated DEGs were enriched in functions associated with development and morphogenesis, from a functional perspective. The present results indicate that gene expression profiles of AD-MSCs were significantly changed compared with HD-MSCs. These changes are probably associated with MSCs' adhesion capacity and development. These results may provide important insights into the role of MSCs in AD pathogenesis.
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关键词
mesenchymal stem cells,aortic dissection,cell therapy,transcriptome profiling,mRNA differential display
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