Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles.

Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles.
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DOI:
10.1038/s41598-018-32154-2
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发表时间:
2018-09-17
期刊:
影响因子:
4.6
通讯作者:
Nerbonne JM
Nerbonne JM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Johnson EK;Matkovich SJ;Nerbonne JM

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人类心脏的四个心腔在维持正常心脏功能方面发挥着不同的作用,并且受到遗传性/获得性心血管疾病的不同影响。为了探索这些功能差异的分子决定因素,我们检测了左(LA)和右(RA)心房、左(LV)和右(RV)心室以及非衰竭人类心脏(N = 8)的室间隔(IVS)的mR NA和lncRNA的表达谱。对配对的心房和心室样本(n = 40)的分析发现,5,747个mRNAs和2,794个lncRNAs差异表达(>1.5倍;fdr < 0.05)。房室(RA/LA)和室壁(RV/LV/IVS)标本之间的差异最大。在每个病例中(例如,LA与LV、LA与RV等),有2,300个mRNAs和1,200个lncRNAs差异表达,相当于总转录本的17-28%。在LA和RA以及LV、RV和IVS中的mRNA/lncRNA表达谱也显示出异质性,尽管差异表达转录本的数量要少得多。在不衰竭的人的心房和心室中,mRNA和lncRNA表达谱的性别差异也很明显。差异表达基因集的基因本体论分类揭示了许多信号通路的小室特异性富集性。
The four chambers of the human heart play distinct roles in the maintenance of normal cardiac function, and are differentially affected by inherited/acquired cardiovascular disease. To probe the molecular determinants of these functional differences, we examined mRNA and lncRNA expression profiles in the left (LA) and right (RA) atria, the left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N = 8). Analysis of paired atrial and ventricular samples (n = 40) identified 5,747 mRNAs and 2,794 lncRNAs that were differentially (>1.5 fold; FDR < 0.05) expressed. The largest differences were observed in comparisons between the atrial (RA/LA) and ventricular (RV/LV/IVS) samples. In every case (e.g., LA vs LV, LA vs RV, etc.), >2,300 mRNAs and >1,200 lncRNAs, corresponding to 17–28% of the total transcripts, were differentially expressed. Heterogeneities in mRNA/lncRNA expression profiles in the LA and RA, as well as in the LV, RV and IVS, were also revealed, although the numbers of differentially expressed transcripts were substantially smaller. Gender differences in mRNA and lncRNA expression profiles were also evident in non-failing human atria and ventricles. Gene ontology classification of differentially expressed gene sets revealed chamber-specific enrichment of numerous signaling pathways.
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