Abstract 18584: Decoding the Regulatory LncRNAs in Neonatal Heart During Perinatal Circulatory Transition

Abstract

Background: Fetal to neonatal transition of heart is an elaborate process, during which, neonatal cardiomyocytes undergo functional maturation and terminal exit from the cell cycle. However, transcriptome programming in neonatal cardiac chambers during perinatal stages is understudied. In particular, the changes in long non-coding RNAs (lncRNAs) in neonatal heart have not been explored. Objective: To achieve transcriptome-wide analysis of lncRNAs in neonatal left ventricle (LV) and right ventricle (RV) during maturation stages using deep RNA-Sequencing Methods: Deep RNA-sequencing was performed on male newborn mouse (C57 BL) LV and RV at 3 time points of perinatal circulatory transition: P0, P3 and P7. Reads were mapped to mouse genome (mm10). The lncRNAs annotated in NONCODE database were identified. Differentially expressed lncRNAs were defined as those with coefficient of variation ≥0.2, at a false discovery rate ≤0.05, and expressed at ≥3 RPKM in at least one sample. Correlated lncRNAs/ gene pairs were identified using Pearson’s (r2≥0.8, P≤0.05). A subset of LncRNAs/gene expression was validated using qRT-PCR. Results: Out of the 70, 983 observed unique lncRNAs, approximately 7000 were identified exhibiting significant variation during maturation windows with highly spatial-temporal dependent expression patterns, including approximately 5000 known and 2000 novel lncRNAs. Notably, 20% of these lncRNAs were located within 50 KB of a protein coding gene. Out of a total of 2400 lncRNAs/gene pairs, 10 % exhibited significantly concordant (lncRNA/gene) expression patterns. These correlated genes were significantly enriched in metabolism, cell cycle and contractility functional ontology. Interestingly, some of these lncRNAs exhibited concordance with their neighboring gene in human tissues with congenital heart defects, suggesting conserved, potentially significant, regulatory function. Conclusions: Transcriptome programming during neonatal heart maturation involves global changes in lncRNAs. Their expression concordance with neighboring protein coding genes implicates potential important regulatory role of lncRNAs in neonatal heart chamber specification and congenital diseases.