TY - JOUR
T1 - Transcriptional atlas of cardiogenesis maps congenital heart disease interactome
AU - Li, Xing
AU - Martinez-Fernandez, Almudena
AU - Hartjes, Katherine A.
AU - Kocher, Jean Pierre A.
AU - Olson, Timothy M.
AU - Terzic, Andre
AU - Nelson, Timothy J.
PY - 2014/7/1
Y1 - 2014/7/1
N2 - 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.
AB - 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.
KW - Cardiogenesis
KW - Congenital heart disease
KW - Heart development
KW - Time course microarray
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=84903396361&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903396361&partnerID=8YFLogxK
U2 - 10.1152/physiolgenomics.00015.2014
DO - 10.1152/physiolgenomics.00015.2014
M3 - Article
C2 - 24803680
AN - SCOPUS:84903396361
SN - 1094-8341
VL - 46
SP - 482
EP - 495
JO - Physiological Genomics
JF - Physiological Genomics
IS - 13
ER -