Abstract

BackgroundMicroRNAs (miRNAs) have been identified as important contributors to the regulation of early fetal cardiopulmonary development. However, miRNA expression profiles during late gestation and the early neonatal period are not fully elaborated in large mammals such as sheep (ovis aries). The aim of this study was to sequence miRNA from cardiopulmonary tissues in late gestation and neonate sheep to identify changes in miRNA expression.MethodsIllumina HiSeq next-generation deep sequencing (NGS) was performed on ovine tissues from the left (LV) and right ventricles (RV), lungs and pulmonary artery (PA) of preterm fetuses (128 days), near-term fetuses (140 days) (term = 148 days) and neonatal lambs (5 days). NGS reads were mapped to the sheep genome (OviAri) and published miRNA sequences.ResultsOf 1345 cardiopulmonary miRNAs that were sequenced, relatively few major shifts in miRNA expression were detected with increased age from near term to neonates, and were confirmed by quantitative real-time PCR: bta-miR-146a (lung), bta-miR-22-3p (lung, LV), hsa-miR-335* (lung, PA), and miR-210 (lung, PA, LV).ConclusionsSequencing of miRNA led to identification of four predominant miRNA in ovine cardiopulmonary tissues which alter expression during late gestation and the early neonatal period, concurrent with important functional changes in heart and lungs.

Highlights

  • MicroRNAs are short noncoding RNAs (18–25 nucleotides) that exert intricate regulation of cellular processes by post-transcriptional inhibition of specific gene expression

  • Of 1345 cardiopulmonary miRNAs that were sequenced, relatively few major shifts in miRNA expression were detected with increased age from near term to neonates, and were confirmed by quantitative real-time PCR: bta-miR-146a, bta-miR-22-3p, hsa-miR-335*, and miR-210

  • Sequencing of miRNA led to identification of four predominant miRNA in ovine cardiopulmonary tissues which alter expression during late gestation and the early neonatal period, concurrent with important functional changes in heart and lungs

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Summary

Introduction

MicroRNAs (miRNA) are short noncoding RNAs (18–25 nucleotides) that exert intricate regulation of cellular processes by post-transcriptional inhibition of specific gene expression. A critical role for miRNAs in mammalian cardiac development has been identified by studies in mice with cardiac-specific deficits of mature miRNAs that disrupt heart morphogenesis in early gestation [2,3,4]. A role for miRNAs in regulating lung development has been identified in rats [7,8,9], and mice [10,11,12]. MicroRNAs (miRNAs) have been identified as important contributors to the regulation of early fetal cardiopulmonary development. MiRNA expression profiles during late gestation and the early neonatal period are not fully elaborated in large mammals such as sheep (ovis aries). The aim of this study was to sequence miRNA from cardiopulmonary tissues in late gestation and neonate sheep to identify changes in miRNA expression

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