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

Eric K Johnson,Scot J Matkovich,Jeanne M Nerbonne

doi:10.1038/s41598-018-32154-2

Eric K Johnson, Scot J Matkovich + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-32154-2

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Journal: Scientific Reports	Publication Date: Sep 17, 2018
Citations: 32	License type: open-access

Affiliation: Washington University in St. Louis

Abstract

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.

Highlights

Transcription of mammalian genomes is complex, and includes the expression of many different RNA species[8]
We used RNA Sequencing (RNASeq) to provide global transcriptome profiling of cardiac mRNAs and long noncoding RNAs (lncRNAs) from transmural tissue samples obtained from the left (LA) and right (RA) atrial appendages, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N = 8)
From each (N = 8) heart, five paired, transmural tissue samples were obtained; these were from the left (LV) and right (RV) ventricles, the left (LA) and right (RA) atrial appendages, and the interventricular septum (IVS)

Summary

Introduction

Transcription of mammalian genomes is complex, and includes the expression of many different RNA species[8]. LncRNAs have not been previously included in analyses of regional differences in transcriptome profiles in the human heart. We used RNA Sequencing (RNASeq) to provide global transcriptome profiling of cardiac mRNAs and lncRNAs from transmural tissue samples obtained from the left (LA) and right (RA) atrial appendages, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N = 8). Differential expression analysis of paired samples (n = 40) identified regional differences in both the mRNA and lncRNA expression profiles in the atria and ventricles, as well as in comparisons between the LA and RA, and the LV, RV and IVS. Functional classification of differentially expressed transcripts revealed chamber-specific differences in numerous signaling pathways

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