Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Probing matters of the heart

17.09.2012
New study of stem cell differentiation could help researchers better understand the genetic basis of heart disease.

The fate of an embryonic stem cell, which has the potential to become any type of body cell, is determined by a complex interaction of genes, proteins that bind DNA, and molecules that modify those genes and proteins.

In a new paper, biologists from MIT and the University of California at San Francisco have outlined how those interactions direct the development of stem cells into mature heart cells. The study, the first to follow heart-cell differentiation over time in such detail, could help scientists better understand how particular mutations can lead to congenital heart defects. It could also assist efforts to engineer artificial heart tissue.

“We’re hoping that some of the information we’ve been able to glean from our study will help us to approach a new understanding of heart development, and also lead to the possibility of using cells that are generated in a dish to replace heart cells that are lost as a consequence of aging and disease,” says Laurie Boyer, an associate professor of biology at MIT and a senior author of the paper, which appears in the Sept. 13 online edition of Cell.

Research in Boyer’s lab focuses on how DNA is organized and controlled in different cell types to create the wide variety of cells that make up the human body.

Inside a cell, DNA is wrapped around proteins called histones, which help control which genes are accessible at any given time. Histones may be tagged with different chemical modifications, which influence whether a particular stretch of DNA is exposed or hidden.

“These modifications cause structural changes that can act as docking sites for other factors to bind,” says Joe Wamstad, a postdoc in Boyer’s lab and one of the lead authors of the Cell paper. “It may make the DNA more or less accessible to manipulation by other factors, helping to ensure that you don’t express a gene at the wrong time.”

In this paper, the researchers found that histone-modification patterns shift rapidly as a stem cell differentiates. Furthermore, the patterns reveal genes that are active at different stages, as well as regulatory elements that control those genes.

Tracking development

To discover those patterns, the researchers grew mouse embryonic stem cells in a lab dish and treated them with proteins and growth factors that drive heart cell development. The cells could be followed through four distinct stages, from embryonic stem cells to fully differentiated cardiomyocytes (the cells that compose heart muscle). At each stage, the researchers used high-throughput sequencing technology to analyze histone modifications and determine which genes were being expressed.

“It’s basically watching differentiation over time in a dish, and being able to take snapshots of that and put it all together to try to understand how the complex process of cardiac commitment is regulated,” Boyer says.

The researchers found that they could identify groups of genes with related functions by comparing their modification patterns and whether they were being transcribed at a particular time. They also identified regulatory regions located far away from the genes they regulate. Many of these regions were located in sections of DNA previously thought to be “junk.” Recent studies have revealed that much of this DNA actually plays important roles in regulating gene expression.

“We’re starting to link genes with the regulatory elements that may be activating them, and beginning to draw a picture of the molecular circuitry that is controlling and driving these cardiac-specific programs — the DNA elements that are important for turning on all the genes that you need to make a heart cell,” Wamstad says.

The team also identified transcription factors — proteins that initiate the expression of genes — that appear to work collaboratively at regulatory regions to drive transcription of genes important for cardiac development. Defects in many of these transcription factors have previously been linked to congenital heart defects.

Linking disease with DNA

Previous genome-wide sequencing studies have revealed genetic variations that are more common in people with congenital heart disease or cardiovascular disease. The data obtained in this study should help researchers figure out why those variations give rise to such diseases.

The findings could also help researchers figure out how to create heart cells for possible therapeutic use, says Richard Lee, a professor of medicine at Harvard Medical School and member of the Harvard Stem Cell Institute.

“It’s a roadmap of how the heart cell develops, and it’s a tremendous achievement,” says Lee, who was not part of the research team. “The work shows that the heart cell develops through coordinated gene expression transitions, and how those transitions are controlled. This study will help us to understand how to make new heart cells, which has been a big challenge for treating heart failure.”

The researchers are now looking for other combinations of transcription factors that are involved in controlling cardiac differentiation. They are also studying variations in the regulatory sequences they identified to figure out how these sequences might give rise to congenital heart disease or susceptibility to cardiovascular disease later in life.

The research was funded by the National Heart, Lung and Blood Institute; the National Institutes of Health; the Lawrence J. and Florence A. DeGeorge Charitable Trust; the Massachusetts Life Sciences Center; and the Pew Scholars Program in the Biomedical Sciences.

Written by: Anne Trafton

Sarah McDonnell | EurekAlert!
Further information:
http://www.mit.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>