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Multi-omics profiling visualizes dynamics of cardiac development and functions

ABSTRACT: The function and phenotype transitions of heart may be specific to one or other chamber. To provide the omics data sets from chambers separately, we conducted spatial transcriptomics of E10.5 hearts to identify unique gene profiles that correspond to distinct anatomical regions in early cardiac development. We obtained curated expression data consisting of 6,798 genes across 332 individual capture spots. We then performed differential gene expression (DGE) analysis between anatomical regions and gene set enrichment analysis of each cluster’s upregulated genes to characterize identified clusters in early cardiogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE213666 | GEO | 2023/01/13

REPOSITORIES: GEO

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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.

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Multi-omics profiling visualizes dynamics of cardiac development and functions

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