Building an Ethnoracial Heart Cell Atlas Throughout Pediatric Development

Grants and Contracts Details

Description

Heart diseases, led by congenital heart defects (CHD), are leading causes of pediatric death(Cunningham, Walton, and Carter 2018). Occurring in 0.8% of livebirths, often with lifelong health issues, CHD consumes over $7 billion annual U.S hospital expenditures.(CDC 2020) While many etiologies of CHD and other childhood heart disease are known and diseased tissues are available from surgical interventions, key molecular responses to disease remain uncertain due to the absence of a reference framework. To address this gap we propose to define heterogenous cellular composition and transcriptional profiles of the healthy heart during post-natal development. The heart undergoes substantial morphologic and hemodynamic changes at birth: closure of embryonic shunts (ductus arteriosus and foramen ovale), establishment of blood flow from the right ventricle into oxygenated lungs, and dramatically increased left ventricular pressure to systemic levels. By year one of life, the human hearts triples in size, right ventricular volumes increase 2-fold, and left ventricular walls thickened.(Hew and Keller 2003a). Somatic growth and puberty further increases heart growth to meet systemic hemodynamic requirements (Janz, Dawson, and Mahoney 2000). Studies of rodent heart development provide some insight into these events(DeLaughter et al. 2016a; Li et al. 2016; Talman et al. 2018), but cannot suffice for human data. Human hearts beat at 10-fold lower rates for decades longer, express different protein isoforms, and distinctly regulate calcium. To capture dynamic changes in cellular and transcriptional landscape of post-natal development we will create a longitudinal pediatric heart atlas using infant, childhood, and adolescent tissues.
StatusFinished
Effective start/end date10/1/219/30/22

Funding

  • Harvard University: $16,452.00

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