Abstract
Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing. The coding genes associated with differentially expressed lncRNAs were mainly involved in metabolic processes and cell proliferation, and also were potentially associated with several key regeneration signalling pathways, including PI3K-Akt, MAPK, Hippo and Wnt. In addition, we identified some correlated targets of highly-dysregulated lncRNAs such as Igfbp3, Trnp1, Itgb6, and Pim3 by the coding-noncoding gene co-expression network. These data may offer a reference resource for further investigation about the mechanisms by which lncRNAs regulate cardiac regeneration.
Highlights
In recent years, the traditional view that the heart is a terminally differentiated organ with no capacity for cardiomyocyte renewal has been emphatically refuted by an increasing number of studies in humans and other mammals [1,2,3]
We found that 685 long noncoding RNA (lncRNA) and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing
Charting the transcriptional profile of lncRNAs in regenerative hearts from neonatal mice is a key step in understanding the role of lncRNAs, and this study was the first to examine the expression of lncRNAs in regenerative hearts
Summary
The traditional view that the heart is a terminally differentiated organ with no capacity for cardiomyocyte renewal has been emphatically refuted by an increasing number of studies in humans and other mammals [1,2,3]. Further study by our group examined the global gene expression patterns of the neonatal mouse heart at key time points (1 and 7 days old) [7] and found several differentially expressed genes involved in transient regeneration of the neonatal mouse heart. A recent study showed that many lncRNAs are expressed in the heart and confirmed the essential role of lncRNAs in the cardiovascular system such as modulating cardiac development [10]. Knocking out the gene lncRNA-H19 has been shown to promote differentiation of parthenogenetic embryonic stem cells to cardiomyocytes with strong heart-like beating [14]. Our understanding of the role of lncRNAs in regeneration of heart tissue in mice is still limited. Two key time points (1 and 7 days old) were selected for the analysis of global lncRNA expression profiles in C57BL/6 mice using next-generation highthroughput RNA sequencing techniques
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