Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Retrovirus in the human genome is active in pluripotent stem cells

24.01.2013
Discovery may offer new insights into the development of stem cell therapies

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 information:
http://www.umassmed.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>