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Physiol Genomics. 2014 Jul 1;46(13):482-95. doi: 10.1152/physiolgenomics.00015.2014. Epub 2014 May 6.

Transcriptional atlas of cardiogenesis maps congenital heart disease interactome.

Author information

1
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota;
2
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota;
3
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota;
4
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota; Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota;
5
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota;
6
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota; Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota; Transplant Center, Mayo Clinic, Rochester, Minnesota; and Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota nelson.timothy@mayo.edu.

Abstract

Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, knowledge of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Mapping the dynamic transcriptional landscape of cardiogenesis from a genomic perspective is essential to integrate the knowledge of heart development into translational applications that accelerate disease discovery efforts toward mechanistic-based treatment strategies. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide dynamic expression landscape of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, revealed stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling known genetic underpinnings of CHD, we deconstructed a disease-centric dynamic interactome encoded within this cardiogenic atlas to identify stage-specific developmental disturbances clustered on regulation of epithelial-to-mesenchymal transition (EMT), BMP signaling, NF-AT signaling, TGFb-dependent EMT, and Notch signaling. Collectively, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease.

KEYWORDS:

cardiogenesis; congenital heart disease; heart development; time course microarray; transcriptome

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