Navigation Links
Probing matters of the heart
Date:9/14/2012

CAMBRIDGE, Mass. 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 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.


'/>"/>
Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology
Source:Eurekalert

Related biology news :

1. Probing the roots of depression by tracking serotonin regulation at a new level
2. Size matters: Large Marine Protected Areas work for dolphins
3. For the rooster, size matters
4. Heart-powered pacemaker could one day eliminate battery-replacement surgery
5. Geological Society of America Cordilleran section meets in the heart of Mexico
6. Cell therapy using patients own bone marrow may present option for heart disease
7. New analysis of premature infants heartbeats, breathing could be cues for leaving NICU
8. Minneapolis Heart Institute selected to participate in Cardiovascular Cell Therapy Research Network
9. Second-generation drug used for hypertension aids heart function independent of blood pressure
10. Scientists develop new technique that could improve heart attack prediction
11. Heart study suggests city center pollution doubles risk of calcium build-up in arteries
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/26/2016)... India and LONDON ... Infosys Finacle, part of EdgeVerve Systems, a product ... and Onegini today announced a partnership to integrate ... solutions.      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ... to provide their customers enhanced security to access ...
(Date:4/15/2016)... , April 15, 2016  A new ... make more accurate underwriting decisions in a fraction ... timely, competitively priced and high-value life insurance policies ... screenings. With Force Diagnostics, rapid testing ... lifestyle data readings (blood pressure, weight, pulse, BMI, ...
(Date:4/13/2016)... CHICAGO , April 13, 2016  IMPOWER physicians ... are setting a new clinical standard in telehealth ... By leveraging the higi platform, IMPOWER patients can ... weight, pulse and body mass index, and, when they ... quick and convenient visit to a local retail location ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... , June 27, 2016 /PRNewswire/ - BIOREM Inc. (TSX-V: ... been advised by its major shareholders, Clean Technology Fund ... United States based venture capital funds ... of Biorem (on a fully diluted, as converted basis), ... disposition of their entire equity holdings in Biorem to ...
(Date:6/27/2016)... ... 27, 2016 , ... Cancer experts from Austria, Hungary, Switzerland, ... a new and helpful biomarker for malignant pleural mesothelioma. Surviving Mesothelioma has just ... now. , Biomarkers are components in the blood, tissue or body fluids ...
(Date:6/27/2016)... , ... June 27, 2016 , ... ... bring innovative medical technologies, services and solutions to the healthcare market. The company's ... of various distribution, manufacturing, sales and marketing strategies that are necessary to help ...
(Date:6/27/2016)... 2016  Liquid Biotech USA ... a Sponsored Research Agreement with The University of ... from cancer patients.  The funding will be used ... with clinical outcomes in cancer patients undergoing a ... be employed to support the design of a ...
Breaking Biology Technology: