Give your heart a break
Dr. Charles Murry explains stem-cell research in his lab at the South Lake Union campus.
Dr. Charles Murry explains stem-cell research in his lab at the South Lake Union campus.Photo by Matthew Toles
UW geneticists have recently come across a discovery that can possibly help alleviate the high prevalence of heart disease, which could have profound implications in the field of medicine.
The researchers discovered the gene MEIS-2 has a crucial role in regulating heart development. In the study, the scientists turned off MEIS-2 in zebra-fish embryos — allowing the usual effects of the gene to be dormant — and found that the zebra-fish hearts did not form properly.
The heart is made of four chambers, but when MEIS-2 was knocked out, the chambers of the zebra-fish hearts did not develop distinctly and the fish had a markedly slower heart rate.
Researchers think they could apply these findings to treatment methods for heart disease in humans.
A damaged guinea-pig heart repaired with human stem cells is tested for electrical synchronization. Dr. Murry believes his team will be ready to perform similar procedures in clinical trials as soon as 2016.
“Heart disease remains the No. 1 killer in the United States, still way ahead of cancer. The disease we spend the most time studying is heart attack, or myocardial infarction,” said Charles Murry, director of the Center for Cardiovascular Biology and co-director of the Institute for Stem Cell and Regenerative Medicine (ISCRM).
Heart attacks are typically caused by a blockage in one of the coronary arteries. However, if detected in time, the artery can be opened and blood flow restored. In spite of this quick action, heart muscle still dies quickly because of the heart’s high metabolism.
Murry said the heart is one of the least regenerative organs in the body. When heart muscle dies, the body makes scar tissue, but scar tissue doesn’t beat, making the heart weaker. A substantial number of people who have heart attacks go on to have heart failure, a syndrome in which the heart doesn’t beat enough to supply a sufficient amount of blood to the body.
“We want to address the root cause of this, which is not having enough muscle cells,” Murry said. “We would like to repopulate the injured heart with new muscle. That’s the big dream. And we want to use stem cells to do that.”
Sharon Paige, doctoral student and lead author of the study, has another aspect of the MEIS-2 testing to consider: the implications of this research on children. Paige, who is doing her residency at Seattle Children’s Hospital, sees many young patients a day who have dealt with heart disease.
“We have so many kids who come to us with these diseases, and many parents come to us asking about the risk of their future children having such diseases,” Paige said. “The more we understand about the genes that regulate cardiac development, the more we will understand about congenital heart disease.”
This research initially started at Murry Lab. The lab focused on determining how DNA was packaged — by winding around protein cores called histones. DNA and proteins combine to form chromatin.
The functions of chromatin led the scientists to ask themselves one major question: Could they find any of the rules on what regulates heart development by how these genes package their DNA?
Once the Murry Lab distinguished a chromatin pattern in known genes relating to heart development, another lab run by Dr. John Stamatoyannopoulos generated a list of which untested genes could also potentially affect heart development.
To check whether any of these genes were significant, Dr. Randall Moon’s lab tested the genes in zebra fish. Dr. Cristi Stoick-Cooper was responsible for the zebra-fish testing.
A monitor displays human embryonic stem cells under a microscope at the South Lake Union Campus. Based on environmental conditions, the cells pictured have the potential to develop into any of more than 100 different human cells.
“We wanted to know if any of the ‘new’ genes were actually required for heart development to proceed,” Stoick-Cooper said. “This list of ‘new’ genes was initially quite long, so we had to whittle it down.”
After testing thousands of zebra-fish embryos, the MEIS-2 gene was chosen for further testing.
“No one had ever done anything on this gene in heart development and seen its effects,” Murry said. “We know all this now because of chromatin signature.”
This study has revealed a gene that can affect how hearts are formed. More importantly, further research on genes with chromatin signatures like MEIS-2 can affect how heart diseases — whether heart attacks or congenital heart diseases — are combated in the future.
Reach contributing writer Jasmine Kim at firstname.lastname@example.org. Twitter: @JasmineKimUW
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