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
Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg
Bio-fabrication of Artificial Blood Vessels with Laser Light
28.08.2015 | Fraunhofer-Institut für Lasertechnik ILT
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.
For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...
It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.
Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
28.08.2015 | Physics and Astronomy
28.08.2015 | Health and Medicine
28.08.2015 | Life Sciences