Congenital Heart Defects; Each year, 9 months of dreams and anticipation shared by millions of parents-to-be turn to despair and fright when learning their child is born with a birth defect; an often-devastating event affecting one out of 20 children born worldwide. The formation of our organs, limbs, and face are the result of carefully choreographed movement and behavior by millions of cells, much like dancers in a troupe. If even a few cells don’t get to the right position and do their job correctly, the end result is a birth defect.
In a new study publish in the scientific journal Nature, a team of researchers at the Gladstone Institutes; hence in collaboration with the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg; which reveal for the first time the full spectrum of cells that come together to make a heart at the earliest stages of embryo formation. They also uncover how the cells are controlled; also how a mutation in just one gene can have catastrophic consequences by affecting a tiny group of cells that make up the organ.
Congenital heart defects
Congenital heart defects are the most common and most lethal human birth defect. Thanks to the advent of a powerful new technology known as single-cell RNA sequencing; so the researchers were finally able to discern the role of tens of thousands of individual cells during the formation of the heart, which is essential to determine how genetic mutations cause disease.
“This sequencing technique allow us to see all the different types of cells present; so at various stages of heart development and help us identify which genes are activate and suppress along the way,” said Casey A. Gifford, Ph.D., a staff scientist at Gladstone who is a senior author on the paper. “They were not only able to uncover the existence of unknown cell types; but we also gain a better understanding of the function and behavior of individual cells information we could never access before.”
The computational prediction turn out to be correct. The team discover that hearts without the Hand2 gene never made cells of the outflow tract; but did make right ventricular cells. In the choreography of the heart; so it is not enough for a cell to be made, it must also get to the right place relative to the other “dancers.” Without Hand 2, right ventricle cells were create; but stuck at their origin, failing to move into the developing heart.
The genetic variations
The study has reveal the mechanisms by which relatively small populations of cells; which are affect during development and lead to defects in the formation of the heart. It also represents a discovery that could not have been possible; so without single-cell RNA sequencing technology. “Single-cell technologies can inform us about how organs form in ways they couldn’t understand before; also can provide the underlying cause of disease associate with genetic variations,” said Gifford.
When children with a birth defect are fortunate enough to survive, the same genetic condition; so that cause the developmental problem can lead to ongoing difficulties; so with maintaining a healthy heart over a lifetime. “They’re beginning to see the long-term consequences in adults, and right now; so they don’t really have any way to treat them,” Srivastava added. “My hope is that if we can understand the genetic causes and the cell types affected; so they could potentially intervene soon after birth to prevent the worsening of their state over time.”
For Srivastava, the holy grail would be to get such a clear picture of the mechanisms; which involve in causing congenital heart defects that they could develop preventive strategies for people who are genetically at risk. “Folic acid being the best paradigm expecting mothers now take higher levels of this vitamin and can successfully prevent nearly two thirds of cases of spina bifida,” he said. “The ultimate goal is to create similar public health measures that could reduce the overall incidence of birth defects through prevention. But first, we have to know where and how to intervene.”