title: Transcriptional atlas of cardiogenesis maps congenital heart disease interactome.
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.
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota;
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota;
authors.forename: Almudena
authors.initials: A
authors.lastname: Martinez-Fernandez
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota;
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hartjes
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota;
authors.forename: Jean-Pierre A
authors.initials: JP
authors.lastname: Kocher
authors.affiliation: 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;
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Olson
authors.affiliation: 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;
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
authors.affiliation: 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.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nelson
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D060066:Protein Interaction Maps / Q000235:genetics*
keywords: cardiogenesis; congenital heart disease; heart development; time course microarray; transcriptome