ScienceDaily (Sep. 14, 2012) 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 rest is here:
Probing matters of the heart: Stem cell differentiation study sheds light on genetic basis of heart disease