Fine-scale Spatiotemporal Mapping of Cellular Regulatory Networks Directing Heart Development

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Principal Investigator: Neil C Chi
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2024
Award: $620,622
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary
Congenital Heart Disease is the most common congenital anomaly in newborn babies, accounting for one third
of all major congenital anomalies. Despite recent congenital heart disease genetic studies highlighting the
critical role of cardiac transcriptional and chromatin regulators during heart development, our understanding of
how these developmental regulators interact to create the dynamic gene regulatory networks that mediate
heart development remains to be fully elucidated. Thus, we propose to define and assay the cardiovascular
developmental regulators and their gene regulatory networks that direct the development of the vast array of
cardiovascular cell types creating the mammalian heart. To achieve this goal, a multi-disciplinary experimental
and computational systems biology approach will be implemented to: (1) elucidate gene regulatory networks
that establish the cardiogenic cellular hierarchy of the developing mammalian heart, (2) investigate the
spatiotemporal organization of the cardiogenic cellular hierarchy during mouse embryogenesis and heart
morphogenesis and (3) functionally examine how distinct cardiovascular developmental sources create specific
cardiovascular lineages contributing to the developing heart.

Terms: <0-4 weeks old><21+ years old><Accounting><Adult><Adult Human><Animals><Assay><Behavior><Bioassay><Biological Assay><Cardiac><Cardiac Malformation><Cardiac development><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cell Body><Cells><Chromatin><Communities><Computer Analysis><Data Set><Development><Early identification><Embryo Development><Embryogenesis><Embryonic Development><Event><Expression Signature><FISH Technic><FISH Technique><FISH analysis><FISH assay><Family><Fluorescence In Situ Hybridization><Fluorescent in Situ Hybridization><Gene Expression Profile><Gene Transcription><Genes><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Genetic study><Goals><Heart><Heart Malformation><Heart Vascular><Human><In Situ><In Vitro><Label><Lead><Maps><Mediating><Mesoderm><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Monitor><Morphogenesis><Murine><Mus><Mutation><Newborn Infant><Newborns><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pb element><Phenotype><Physicians><Population Heterogeneity><Process><Progenitor Cells><RNA Expression><RNA Seq><RNA sequencing><RNAseq><Regulatory Pathway><Research><Role><Societies><Source><Specific qualifier value><Specified><Structure><Systems Biology><Transcription><Transgenic Organisms><Validation><abnormal heart development><adulthood><cardiogenesis><cell type><circulatory system><computational analyses><computational analysis><computer analyses><congenital anomaly><congenital cardiac abnormality><congenital cardiac anomalies><congenital cardiac disease><congenital cardiac disorder><congenital cardiac malformation><congenital heart abnormality><congenital heart anomaly><congenital heart disease><congenital heart disorder><congenital heart malformation><developmental><diverse populations><gene expression pattern><gene expression signature><gene network><gene regulatory network><genome mutation><heart development><heart formation><heavy metal Pb><heavy metal lead><heterogeneous population><human pluripotent stem cell><improved><insight><morphogenetic process><multidisciplinary><newborn child><newborn children><patient oriented outcomes><patient population><population diversity><progenitor><progenitor cell model><progenitor cell population><progenitor model><progenitor population><reconstruction><single cell analysis><social role><spatiotemporal><stem and progenitor cell model><stem and progenitor cell population><stem cell based model><stem cell derived model><stem cell model><stem cell population><stem cells><transcriptional profile><transcriptional signature><transcriptome sequencing><transcriptomic sequencing><transgenic><translational framework><validations>