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出 处:《中华肝脏病杂志》2015年第11期849-853,共5页Chinese Journal of Hepatology
基 金:国家自然科学基金(30971472、31171310)
摘 要:目的比较分析人肝脏前体细胞定向肝实质细胞分化过程中基因表达的变化。方法分别提取体外培养的人胚肝脏前体细胞及体外诱导分化后具有功能的肝实质样细胞的mRNA,通过基因芯片技术检测二者基因表达的变化,利用火山图及DAVID软件分析差异表达基因与细胞功能的相互关系。结果与人胚肝脏前体细胞相比,肝实质样细胞中1878个核苷酸序列表达上调,1441个核苷酸序列表达下调。表达上调的基因主要涉及糖代谢、凋亡调节、血管发育、细胞迁移、蛋白磷酸化等生物学过程;表达下调的基因则与细胞周期、DNA代谢、细胞骨架的组装、细胞周期的调控、染色体的分离有关。结论肝实质样细胞中与肝实质细胞功能相关的基因表达明显增加,而与细胞周期调控的基因表达下降。Objective To identify the genes playing a functional role in differentiation of human hepatic progenitor cells to hepatocytes by comparing the gene expression and functional profiles of the two cell types. Methods mRNA was isolated from human fetal hepatic progenitor cells (hFHPCs) and functional hepatocyte-like cells (HLCs) that had diferenfiated from hFHPCs. Global gene expression profiling was performed on triplicate samples of each cell type. The differential gene expression was analyzed using volcano plot filtering and functional annotation was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results Compared to the hFHPCs, the HLCs had a total of 1878 significantly up-regulated genes and 1441 significantly down-regulated genes. The up-regulated genes included functional groups related to the hexose metabolic process, positive regulation of apoptosis, angiogenesis, regulation of cell motion, and protein amino acid phosphorylation. The down-regulated genes included functional groups related to cell cycle, DNA metabolic process, cytoskeleton organization, regulation cell cycle, and chromosome segregation. Conclusion Differentiation of HLCs fi'om hFHPCs may involve increased expression of genes related to hepatocyte function and decreased expression of genes related to cell cycle regulation.
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