A retrovirus called HERV-H, which inserted itself into the human genome millions of years ago, may play an important role in pluripotent stem cells, according to a new study published in the journal Retrovirology by scientists at UMass Medical School. Pluripotent stem cells are capable of generating all tissue types, including blood cells, brain cells and heart cells.
The discovery, which may help explain how these cells maintain a state of pluripotency and are able to differentiate into many types of cells, could have profound implications for therapies that would use pluripotent stem cells to treat a range of human diseases.
"What we've observed is that a group of endogenous retroviruses called HERV-H is extremely busy in human embryonic stem cells," said Jeremy Luban, MD, the David L. Freelander Memorial Professor in HIV/AIDS Research, professor of molecular medicine and lead author of the study. "In fact, HERV-H is one of the most abundantly expressed genes in pluripotent stem cells and it isn't found in any other cell types."
In the study, Dr. Luban and colleagues describe how RNA from the HERV-H sequence makes up as much as 2 percent of the total RNA found in pluripotent stem cells. The HERV-H sequence is controlled by the same factors that are used to reprogram skin cells into induced pluripotent stem (iPS) cells, a discovery that garnered the 2012 Nobel Prize in Physiology or Medicine. "In other words, HERV-H is a new marker for pluripotency in humans that has the potential to aid in the development of iPS cells and transform current stem cell technology," said Luban.
When a retrovirus infects a cell, it inserts its own genes into the chromosomal DNA of the host cell. As a result, the host cell treats the viral genome as part of its own DNA sequence and begins making the proteins required to assemble new copies of the virus. And because the retrovirus is now part of the host cell's genome, when the cell divides, the virus is inherited by all daughter cells.
In rare cases, it's believed that retroviruses can infect human sperm or egg cells. If this happens, and if the resulting embryo survives, the retrovirus can become a permanent part of the human genome, and be passed down from generation to generation. Scientists estimate that as much as 8 percent of the human genome may be comprised of extinct retroviruses left over from infections that occurred millions of years ago. Yet these sequences of fossilized retrovirus were thought to have no discernible functional value.
"The human genome is filled with retrovirus DNA thought to be no more than fossilized junk," said Luban. "Increasingly, there are indications that these sequences might not be junk. They might play a role in gene expression after all."
An expert in HIV and other retroviruses, Luban and his colleagues were seeking to understand if there was a rationale behind where, in the expansive human genome, retroviruses inserted themselves. Knowing where along the chromosomal DNA retroviruses might attack could potentially lead to the development of drugs that protect against infection; better gene therapy treatments; or novel biomarkers that would predict where a retrovirus would insert itself in the genome, said Luban.
Turning these same techniques on the retrovirus sequences already in the human genome, they discovered a sequence, HERV-H, that appeared to be active. "The sequences weren't making proteins because they had been so disrupted over millions of years, but they were making these long, noncoding RNAs," said Luban.
Specifically, the HERV-H sequence was making abundant amounts of RNA in human embryonic stem cells—and only stem cells. In total, there are more than 1,000 HERV-H retrovirus genomes scattered throughout the human genome. The Luban lab also found high levels of HERV-H RNA in some iPS cells. Other iPS cells, perhaps those lines that were not sufficiently reprogrammed to pluripotency, had lower levels of the HERV-H RNA, another indication that HERV-H may be an important marker for pluripotency.
Interestingly, the HERV-H genes that were expressed in human pluripotent stem cells are only found in the human and chimpanzee genomes, indicating that HERV-H infected a relatively recent ancestor to humans, said Luban.
"Once upon a time HERV-H was an invader to our genome and perhaps caused diseases like AIDS or cancer," said Luban. "Now it seems that a kind of détente has been reached. Not only that, but this ancient invader may one day be exploited by clinicians to cure people of a wide range of diseases using stem cell therapies."
Luban and colleagues will next try to determine the specific mechanisms by which HERV-H contributes to pluripotency.
About the University of Massachusetts Medical School
The University of Massachusetts Medical School has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $250 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.
Jim Fessenden | EurekAlert!
Further reports about: > DNA > Medical Wellness > Memorial > Nobel Prize > RNA > Retrovirus > blood cell > brain cell > cell type > chromosomal DNA > embryonic stem > embryonic stem cell > human embryonic stem cell > human genome > iPS cells > pluripotent stem > pluripotent stem cells > skin cell > stem cells
Carbon nanotubes grown in combustion flames
02.06.2015 | Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University
Constructing complex molecules with atomic precision
02.06.2015 | Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
Researchers at the U.S. Department of Energy's Princeton Plasma Physics Laboratory (PPPL) have for the first time simulated the formation of structures called "plasmoids" during Coaxial Helicity Injection (CHI), a process that could simplify the design of fusion facilities known as tokamaks.
The findings, reported in the journal Physical Review Letters, involve the formation of plasmoids in the hot, charged plasma gas that fuels fusion reactions....
Many joining and cutting processes are possible only with lasers. New technologies make it possible to manufacture metal components with hollow structures that are significantly lighter and yet just as stable as solid components. In addition, lasers can be used to combine various lightweight construction materials and steels with each other. The Fraunhofer Institute for Laser Technology ILT in Aachen is presenting a range of such solutions at the LASER World of Photonics trade fair from June 22 to 25, 2015 in Munich, Germany, (Hall A3, Stand 121).
Lightweight construction materials are popular: aluminum is used in the bodywork of cars, for example, and aircraft fuselages already consist in large part of...
Using ultrashort laser pulses, scientists in Max Planck Institute of Quantum Optics have demonstrated the emission of extreme ultraviolet radiation from thin dielectric films and have investigated the underlying mechanisms.
In 1961, only shortly after the invention of the first laser, scientists exposed silicon dioxide crystals (also known as quartz) to an intense ruby laser to...
The only professorship in Germany to date, one master's programme, one laboratory with worldwide unique equipment and the corresponding research results: The University of Würzburg is leading in the field of biofabrication.
Paul Dalton is presently the only professor of biofabrication in Germany. About a year ago, the Australian researcher relocated to the Würzburg department for...
Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.
Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...
01.06.2015 | Event News
20.05.2015 | Event News
18.05.2015 | Event News
02.06.2015 | Life Sciences
02.06.2015 | Life Sciences
02.06.2015 | Power and Electrical Engineering