Scientists have gained a new understanding of how mutations of a gene known as TBX5 can lead to congenital heart disease, sharing their findings in Developmental Cell.
These latest discoveries, the team hopes, may shine light on new ways to prevent some birth defects from ever happening. After mutating TBX5 genes and “coaxing” human induced pluripotent stem cells to become heart cells, the group used single-cell RNA sequencing to monitor how the ongoing mutation affected different genes. Some genes expressed at higher or lower levels when encountering the mutation, and some cells didn’t respond at all. This provided new context into what, exactly, happens inside the human body because of the mutation.
The researchers have been evaluating TBX5 mutations for quite some time now, but they had mostly used mice models in the past. This study represents a step forward, allowing the scientists to study these mutations in human cells.
“This is really the first time we’ve been able to study this genetic mutation in a human context,” senior author Benoit Bruneau, PhD, director of the Gladstone Institute of Cardiovascular Disease and a professor at the University of California San Francisco, said in a prepared statement. “The mouse heart is a good proxy for the human heart, but it’s not exactly the same, so it’s important to be able to carry out these experiments in human cells.”
Bruneau et al. see this study as a crucial step forward, one that could lead to a future where physicians are able to stop congenital heart disease from even occurring.
“We now have a better understanding of what genes are improperly deployed in some cases of congenital heart disease,” Bruneau said. “Eventually, this might help us get a handle on how to modulate genetic networks to prevent or treat the disease.”
The full Developmental Cell analysis is available here.
Michael has more than 16 years of experience as a professional writer and editor. He has written at length about cardiology, radiology, artificial intelligence and other key healthcare topics.