Project description:Comprehensive detail of the molecular mechanisms that govern heart development is essential for identifying the etiology of congenital heart disease. We used high-throughput quantitative proteomics to measure temporal changes in the cardiac proteome at eight critical stages of murine embryonic heart development. We identified more than 7,300 proteins, assessed global temporal changes in protein expression, identified cardiac protein interaction networks, and linked protein dynamics with molecular pathways. Using this dataset, we identified and defined a function for the mevalonate pathway in the regulation of embryonic cardiomyocyte proliferation and cell signaling. Overall, our proteomic datasets are an invaluable resource for studying molecular events that regulate embryonic heart development and that contribute to congenital heart disease.
Project description:Chromatin State Profilining using multiple histone modifications in human embryonic heart tissue spanning 4 post conception weeks (pcw) to 8 pcw
Project description:Human heart tissue transcriptome was analyzed over a developmental period of 4-8 weeks post-conception. The analysis identifies several modules of co-expressed genes. These modules were tested for significance and disease relevance using other publically available data. This gene expression data was also integrated with the epigenetic data generated in this study to elucidate complex regulatory networks.
Project description:In order to understand genes expressed during posterior second heart field (pSHF) development, we performed microdissections of the region for transcriptomic analysis at mouse embryonic day 9.5.
Project description:Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, the transcriptional landscape of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide expression profile of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, prioritized stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling the bioinformatics of the congenital heart disease interactome, we deconstructed disease-centric regulatory networks encoded within this cardiogenic atlas to reveal stage-specific developmental disturbances clustered on epithelial-to-mesenchymal transition (EMT), BMP regulation, NF-AT signaling, TGFb-dependent induction, and Notch signaling. Therefore, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease. To interrogate the temporal and spatial expression profiles across the entire genome during mammalian heart development, we designed a time-course microarray experiment using the mouse model at defined stages of cardiogenesis, starting with embryonic stem cells (ESC, R1 stem cell line), early embryonic developmental stages: E7.5 whole embryos, E8.5 heart tubes, left and right ventricle tissues at E9.5, E12.5, E14.5, E18.5 to 3 days after birth (D3) and adult heart (Figure 1A). At each time point, microarray experiments were performed on triplicate biological samples. Starting at E9.5, tissue samples from left ventricles (LV) and right ventricles (RV) were microdissected for RNA purification and microarray analysis to determine spatially differential gene expression between LV and RV during heart development.
Project description:We performed a detailed analysis of gene expression in the 2-day (HH12) embryonic chick heart. RNA-seq of 13 microdissected heart regions reveals regionalised expression of about 15,000 genes (Dataset 1). Of these, 131 genes that are differentially expressed (FPKM ≥20, fold change ≥1.1-4.0) within a region compared to the other 12 regions were studied by in situ hybridisation (bold text in Dataset 1) and used to generate a 3D molecular map of the heart at this stage of development.