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Molecular atlas of postnatal mouse heart development

ABSTRACT: Shotgun proteomics analysis of heart left ventricles from mice of ages 1, 4, 9, and 23 days (P01, P04, P09, and P23, respectively). The data set contains two experiments, first with P01, P04, and P09, and second with P01, P04, P09, and P23.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Risto Kostiainen Heikki Ruskoaho Markku Varjosalo

PROVIDER: MSV000082290 | MassIVE | Thu Apr 19 05:16:00 BST 2018

SECONDARY ACCESSION(S): PXD009544

REPOSITORIES: MassIVE

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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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Molecular atlas of postnatal mouse heart development

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