Scientists map the genomic blueprint of the heart

September 13, 2012
This shows a group of embryonic stem cells currently being transformed into beating heart muscle cells, or cardiomyocytes in a petri dish. Credit: Jeff Alexander

Scientists at the Gladstone Institutes have revealed the precise order and timing of hundreds of genetic "switches" required to construct a fully functional heart from embryonic heart cells—providing new clues into the genetic basis for some forms of congenital heart disease.

In a study being published online today in the journal Cell, researchers in the laboratory of Gladstone Senior Investigator Benoit Bruneau, PhD, employed stem cell technology, next-generation DNA sequencing and to piece together the instruction manual, or "genomic blueprint" for how a heart becomes a heart. These findings offer renewed hope for combating life-threatening heart defects such as arrhythmias () and ventricular septal defects ("holes in the heart").

" are the most common type of birth defects—affecting more than 35,000 newborn babies in the United States each year," said Dr. Bruneau, who is the associate director of at Gladstone, an independent and nonprofit biomedical-research organization. "But how these defects develop at the has been difficult to pinpoint because research has focused on a small set of genes. Here, we approach with a wide-angle lens by looking at the entirety of the that gives heart cells their unique identity."

"Congenital heart defects are the most common type of birth defects—affecting more than 35,000 newborn babies in the United States each year," said Dr. Bruneau, who is the associate director of cardiovascular research at Gladstone, an independent and nonprofit biomedical-research organization. "But how these defects develop at the genetic level has been difficult to pinpoint because research has focused on a small set of genes. Here, we approach heart formation with a wide-angle lens by looking at the entirety of the genetic material that gives heart cells their unique identity."

The video will load shortly.
The video shows beating heart muscle cells, or cardiomyoctes, at day 10 of differentiation. Credit: Jeff Alexander

In this research—conducted in large part at Gladstone's Roddenberry Center for Stem Cell Biology and Medicine, as well as in collaboration with the laboratory of Laurie Boyer, PhD, at the Massachusetts Institute of Technology—the scientists took embryonic stem cells from mice and reprogrammed them into beating heart cells by mimicking embryonic development in a petri dish. Next, they extracted the DNA from developing and mature heart cells, using an advanced gene-sequencing technique called ChIP-seq that lets scientists "see" the epigenetic signatures written in the DNA.

"But simply finding these signatures was only half the battle—we next had to decipher which aspects of heart formation they encoded," said Jeffrey Alexander, a Gladstone and UCSF graduate student and one of the paper's lead authors. "To do that, we harnessed the computing power of the Gladstone Bioinformatics Core. This allowed us to take the mountains of data collected from gene sequencing and organize it into a readable, meaningful blueprint for how a heart becomes a heart."

The team made some unexpected discoveries. They found that groups of genes appear to work together in in a coordinated fashion—switching on and off as a group at designated times during embryonic development. The scientists not only identified a whole host of new genes involved in heart formation, but they also refined exactly how these newly discovered genes interact with previously known genes.

The human-health implications of mapping the genomic blueprint of the heart are far reaching. Now that scientists understand how these genes control the heart, they can begin to piece together how heart disease disrupts this regulation. Eventually, they can look for therapies to prevent, interrupt or counteract those disruptions in children who suffer from congenital heart disease.

"Our findings reveal new clues as to how complex genetic and epigenetic patterns are precisely regulated during heart formation," said Dr. Boyer. "In particular, our identification of key segments of the genome that contribute to this process will hopefully allow us to identify the genetic causes of many forms of congenital heart disease—an important first step in the fight against this devastating disease."

"Next, we hope to examine the DNA of patients living with , in the hopes that we can pinpoint the specific genetic disruption that caused their heart defect," said Dr. Bruneau, who is also a professor of pediatrics at the University of California, San Francisco, with which Gladstone is affiliated. "Once we identify that disruption, we can begin exploring ways to restore normal gene function during early heart formation—and reduce the number of babies born with debilitating, and sometimes fatal, congenital heart defects."

Explore further: Researchers find genetic mechanism linked to congenital heart disease

Related Stories

Researchers find genetic mechanism linked to congenital heart disease

January 22, 2012
Scientists at the Gladstone Institutes have identified a finely tuned mechanism by which fetal heart muscle develops into a healthy and fully formed beating heart—offering new insight into the genetic causes of congenital ...

Scientist discovers genetic factor implicated in heartbeat defect

August 8, 2011
A scientist at the Gladstone Institutes has discovered how gene regulation can make hearts beat out of sync, offering new hope for the millions who suffer from a potentially fatal heart condition.

New mouse model helps explain gene discovery in congenital heart disease

June 26, 2012
Scientists now have clues to how a gene mutation discovered in families affected with congenital heart disease leads to underdevelopment of the walls that separate the heart into four chambers. A Nationwide Children's Hospital ...

Recommended for you

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Inhibiting a protein found to reduce progression of Alzheimer's and ALS in mice

August 17, 2017
(Medical Xpress)—A team of researchers with Genetech Inc. and universities in Hamburg and San Francisco has found that inhibiting the creation of a protein leads to a reduction in the progression of Alzheimer's disease ...

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.