Project description:As the fetal heart develops, cardiomyocyte proliferation potential decreases while fatty acid oxidative capacity increases, a highly regulated transition known as cardiac maturation. Small noncoding RNAs, such as microRNAs (miRNAs), contribute to the establishment and control of tissue-specific transcriptional programs. However, small RNA expression dynamics and genome wide miRNA regulatory networks controlling maturation of the human fetal heart remain poorly understood. Transcriptome profiling of small RNAs revealed the temporal expression patterns of miRNA, piRNA, circRNA, snoRNA, snRNA and tRNA in the developing human heart between 8 and 19 weeks of gestation. Our analysis revealed that miRNAs were the most dynamically expressed small RNA species throughout mid-gestation. Cross-referencing differentially expressed miRNAs and mRNAs predicted 6,200 mRNA targets, 2134 of which were upregulated and 4066 downregulated as gestation progresses. Moreover, we found that downregulated targets of upregulated miRNAs predominantly control cell cycle progression, while upregulated targets of downregulated miRNAs are linked to energy sensing and oxidative metabolism. Furthermore, integration of miRNA and mRNA profiles with proteomes and reporter metabolites revealed that proteins encoded in mRNA targets, and their associated metabolites, mediate fatty acid oxidation and are enriched as the heart develops.This study revealed the small RNAome of the maturing human fetal heart. Furthermore, our findings suggest that coordinated activation and repression of miRNA expression throughout mid-gestation is essential to establish a dynamic miRNA-mRNA-protein network that decreases cardiomyocyte proliferation potential while increasing the oxidative capacity of the maturing human fetal heart.
Project description:We report an integrative analysis of miRNA-seq and mRNA-seq to identify miRNAs, genes, and miRNA-mRNA interactions for human atrial aging (AA). We found that seven miRNAs (4 upregulation and 3 downregulation) and 42 genes (23 upregulation and 19 downregulation) show differential expression between older samples and younger samples in human right atrial tissues. Pearson correlation analysis identified 114 pairs of putative miRNA-mRNA interactions for AA. Pathway enrichment analysis identified three important pathways including rhythmic process, senescence and autophagy in cancer, and positive regulation of cytokine biosynthetic process. Our study revealed novel miRNA-mRNA interaction networks and signaling pathways for AA, providing novel insights into the development of human AA. This dataset includes data generation and processing steps for the miRNA-seq data generated from twelve SR samples.
Project description:Objective: Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available regarding the relationship of miRNAs expression profile, biological pathway and cellular phenotype during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA expression profile in human adipocytes is related to adipogenesis and to test whether miRNA profile in human subcutaneous adipose tissue is associated to human obesity and co-morbidities. Keywords: miRNA expression
Project description:We have identified several nucleotide motifs (caug, cgggag=S2) that promote exosome sorting of miRNA in different cell types including brown adipocytes. In order to identify which proteins might recognize and bind to these motifs, we have performed co-precipitations of proteins binding biotinylated forms of miRNAs containing the aforementioned motifs or none - using streptavidin beads incubated with brown adipocytes cell lysates. We have included two types of controls: negative poly-A control and a scramble miRNA.