Chan Zuckerberg Initiative

You can’t use a rat to figure out how a child’s heart develops from fetus to adulthood, so researchers are working with human tissue, thanks to the Chan Zuckerberg Initiative (CZI), which has awarded Harvard Medical School a $1.75 million grant to support a project titled “Building a Pediatric Healthy Heart Cell Atlas Across Ancestries.”

“We intuitively know that the biology of children is different from adults and yet quite little is known about the actual cellular or molecular mechanisms that differ,” says Jonah Cool, PhD, program officer for the Single-Cell Biology program at CZI. “Funding pediatric research will help us decipher the origins of many childhood diseases, including heart diseases.”

The project will be led by Christine Seidman, AB ’74, MD, the Thomas W. Smith Professor of Medicine at Brigham and Women’s Hospital and a professor of genetics in the Blavatnik Institute at HMS. Seidman notes that congenital heart defects (CHDs) occur in just under 1% of births, but CHDs and other heart diseases are leading causes of pediatric deaths and cost more than $7 billion annually in U.S. health care expenditures.

Although researchers have been able to study diseased heart tissue before, until now there has been no prolonged observation of how the pediatric heart develops in humans, and the changes in the development of a child’s heart are dramatic—the heart triples in size in the first year of life and continues to grow with the child. Changes in the properties of the heart must occur to support its rapid growth and also to supply increased energy requirements of growing tissues throughout the body. The heart changes again when a child hits puberty so the organ can continue to pump blood to serve the needs of an adult for decades.

Although researchers have been able to study diseased heart tissue before, until now there has been no prolonged observation of how the pediatric heart develops in humans, and the changes in the development of a child’s heart are dramatic—the heart triples in size in the first year of life and continues to grow with the child. Changes in the properties of the heart must occur to support its rapid growth and also to supply increased energy requirements of growing tissues throughout the body. The heart changes again when a child hits puberty so the organ can continue to pump blood to serve the needs of an adult for decades.

“Dr. Seidman’s project sheds an important light on how pediatric heart research can improve our understanding of how a healthy heart develops, leading to disease detection and treatments,” Cool says.

Researchers previously studied rodent hearts, but the human heart structure and function are quite different. For example, a rat’s heart beats 10 times faster than the heart of a child. That’s why researchers need to find out how the human heart develops from fetus to newborn to early childhood to adolescence to adulthood. And while the newborn heart is similar in structure to the adult heart, the chemistry of the organ changes as the child develops.

“Today we have very few insights into how the healthy human heart changes throughout childhood growth and adolescent maturation,” Seidman says. “Support from the CZI will enable an international collaboration to define the cells of the human heart and their molecular properties during normal physiologic growth.”

Seidman says the researchers intend to freely share their data with the scientific community so as to improve insights into the consequences of pediatric heart disease and ultimately advance new treatment opportunities for many children with these serious conditions.