成人与新生儿来源的间充质干细胞circRNAs差异表达谱分析及功能预测
Differential expression profile and functional prediction of circRNAs in adult versus fetal mesenchymal stem cells
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摘要: 目的 筛选成人与新生儿来源的间充质干细胞(mesenchymal stem cells,MSCs)的差异表达circRNAs,为进一步探究circRNAs在增龄调控MSCs细胞命运中的作用及机制提供理论基础。方法 通过对微阵列数据GSE122178中的3例成人骨髓来源的间充质干细胞样本、3例围生期新生儿脐带血来源的间充质干细胞样本进行生物信息学分析,筛选差异表达的circRNAs,并预测其生物学功能和作用机制。结果 新生儿脐带血来源的间充质干细胞与成人骨髓来源的间充质干细胞相比,66个circRNAs表达显著上调,107个circRNAs表达显著下调。其中hsa_circ_0080170表达上调最显著,hsa_circ_0060055表达下调最显著。hsa_circ_0080170具有6个下游miRNAs结合位点,714个靶基因;hsa_circ_0060055具有28个下游miRNAs结合位点,591个靶基因。KEGG分析显示,hsa-miR370和hsa-miR203a的靶基因显著富集到多能干细胞调控通路等31条信号通路;hsa-miR1225-5p和hsa-miR197靶基因显著富集到肌动蛋白细胞骨架调控通路等17条信号通路。结论 成人和围生期新生儿来源的间充质干细胞circRNAs表达谱的差异提示,hsa_circ_0080170和hsa_circ_0060055可能在间充质干细胞的增龄调控中发挥作用。Abstract: Objective To screen the differentially expressed circRNAs in adult and fetal mesenchymal stem cells and explore the role and mechanism of circRNAs in regulating aging in MSCs. Methods Through bioinformatics analysis to 3 adult bone marrow-derived mesenchymal stem cell samples and 3 fetal cord blood-derived mesenchymal stem cell samples from microarray data GSE122178,the differentially expressed circRNAs were screened and its biological function and mechanism were predicted. Results Compared to adult MSCs,the expressions of 66 circRNAs in fetal MSCs were significantly up-regulated while the other 107 circRNAs were significantly down-regulated.Among them,the expression of hsa_circ_0080170 was up-regulated and the expression of hsa_circ_0060055 was down-regulated most significantly.hsa_circ_0080170 had 6 downstream miRNAs binding sites and 714 target genes;hsa_circ_0060055 had 28 downstream miRNAs binding sites and 591 target genes.KEGG analysis showed that the target genes of hsa-miR370 and hsa-miR203a were significantly enriched to 31 signal pathways such as signaling pathways regulating pluripotency of stem cells;hsa-miR1225-5p and hsa-miR197 target genes were significantly enriched to 17 signal pathways such as regulation of actin cytoskeleton. Conclusion Through the circRNAs differential expression profiles in adult and fetal mesenchymal stem cells,we have predicted that hsa_circ_0080170 and hsa_circ_0060055 may play a role in regulating the cell fate of mesenchymal stem cells with aging.
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