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Whole genome expression differences in human left and right atria ascertained by RNA sequencing.

ABSTRACT: The left and right atria have different susceptibilities toward developing arrhythmias, with left atrial arrhythmias more commonly observed. To understand the molecular basis for such differences, we catalogued micro (mi)RNA and mRNA expression differences by next generation sequencing.Four human left-right atrial pairs were subjected to whole-genome expression analyses via next-generation sequencing of small RNAs, including miRNAs, and poly-A-enriched mRNAs. Using a paired sample design, significant differences in the expression of 32 miRNAs were found in between the left and right atria at a probability value of <0.01. Hsa-miR-143 was the most highly expressed miRNA in the atria, as quantified by RNA sequencing. There were 746 and 2292 differentially expressed mRNAs between the left and right atria at false discovery rates of <0.001 and <0.05, respectively. Transcription factor binding elements within 2 kb of RefSeq genes were determined and specific motifs were identified that were enriched in differentially expressed genes. Similarly, specific miRNA target sequences in 3' UTRs were also enriched in differentially expressed genes. In addition, 11 novel noncoding RNAs of unknown function were found to be differentially expressed between the left and right atria.There are significant differences in miRNA and mRNA expression profiles between the left and right atria, which may yield insight into increased the arrhythmogenesis of the left atria.

SUBMITTER: Hsu J

PROVIDER: S-EPMC3380143 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Whole genome expression differences in human left and right atria ascertained by RNA sequencing.

Hsu Jeffrey J Hanna Peter P Van Wagoner David R DR Barnard John J Serre David D Chung Mina K MK Smith Jonathan D JD

Circulation. Cardiovascular genetics 20120403 3

<h4>Background</h4>The left and right atria have different susceptibilities toward developing arrhythmias, with left atrial arrhythmias more commonly observed. To understand the molecular basis for such differences, we catalogued micro (mi)RNA and mRNA expression differences by next generation sequencing.<h4>Methods and results</h4>Four human left-right atrial pairs were subjected to whole-genome expression analyses via next-generation sequencing of small RNAs, including miRNAs, and poly-A-enric ...[more]

PMID: 22474228

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Project description:BACKGROUND:Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. METHODS:We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. RESULTS:We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGF? family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c(+/-) atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. CONCLUSIONS:Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining "leftness" in the atrium in adult murine and human hearts.

Dataset Information

Whole genome expression differences in human left and right atria ascertained by RNA sequencing.

Publications

Whole genome expression differences in human left and right atria ascertained by RNA sequencing.

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