Transcriptional atlas of cardiogenesis maps congenital heart disease interactome

Xing Li, Almudena Martinez-Fernandez, Katherine A. Hartjes, Jean Pierre A. Kocher, Timothy M. Olson, Andre Terzic, Timothy J. Nelson

Research output: Contribution to journalArticle

29 Scopus citations

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 stagespecific 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.

Original languageEnglish (US)
Pages (from-to)482-495
Number of pages14
JournalPhysiological Genomics
Volume46
Issue number13
DOIs
StatePublished - Jul 1 2014

Keywords

  • Cardiogenesis
  • Congenital heart disease
  • Heart development
  • Time course microarray
  • Transcriptome

ASJC Scopus subject areas

  • Physiology
  • Genetics

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