Abstract
Heart development is a complex process, tightly regulated by numerous molecular mechanisms. Key components of the regulatory network underlying heart development are transcription factors (TFs) and microRNAs (miRNAs), yet limited investigation of the role of miRNAs in heart development has taken place. Here, we report the first parallel genome-wide profiling of polyadenylated RNAs and miRNAs in a developing murine heart. These data enable us to identify dynamic activation or repression of numerous biological processes and signaling pathways. More than 200 miRNAs and 25 long non-coding RNAs were differentially expressed during embryonic heart development compared to the mature heart; most of these had not been previously associated with cardiogenesis. Integrative analysis of expression data and potential regulatory interactions suggested 28 miRNAs as novel regulators of embryonic heart development, representing a considerable expansion of the current repertoire of known cardiac miRNAs. To facilitate follow-up investigations, we constructed HeartMiR (http://heartmir.sysbiolab.eu), an open access database and interactive visualization tool for the study of gene regulation by miRNAs during heart development.
Highlights
Heart development comprises a series of temporally and spatially coordinated processes, involving distinct cell populations.[1]
More than 200 miRNAs and 25 long non-coding RNAs were differentially expressed during embryonic heart development compared to the mature heart; most of these had not been previously associated with cardiogenesis
Alternative to the data-driven clustering approach connecting the temporal profiles of differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs), we aimed to link individual miRNAs to specific genes that are known to be involved in heart development and that we examined earlier (Figure 2)
Summary
Heart development comprises a series of temporally and spatially coordinated processes, involving distinct cell populations.[1] In mice, a primitive linear heart tube is formed from the lateral mesoderm at embryonic day 8 (E8.0). Extrinsic signaling molecules, such as bone morphogenic proteins (BMPs) in the anterior lateral plate mesoderm, are essential for the initiation of myocardial differentiation and cardiac developmental processes.[9] More recently, small non-coding RNAs, termed microRNAs (miRNAs) have been recognized as key regulators of organ development in several organisms, such as Caenorhabditis elegans, Drosophila melanogaster, and humans.[10,11,12,13]
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