Step-by-step description of the transformation of an embryonic cell into a cardiomyocyte
From an embryonic stem cell to a cardiomyocyte:
a genomic map of the heart has been compiled
LifeSciencesToday based on MIT news: Probing matters of the heartThe fate of embryonic stem cells capable of becoming any type of body cells is determined by the complex interaction of genes, proteins that bind to DNA, and molecules that modify these genes and proteins.
In a new article published online in the journal Cell (Wamstad et al., Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage), biologists from the Massachusetts Institute of Technology (Massachusetts Institute of Technology) and the University of California at San Francisco described how these interactions control the transformation of embryonic stem cells into mature heart cells – cardiomyocytes. The study, which for the first time tracks the differentiation of heart cells in a temporal aspect in such detail, can help scientists better understand how certain mutations lead to congenital heart defects, as well as create artificial heart tissue.
"We hope that the information we were able to extract from our study will help to achieve a new understanding of heart development, and also open up the possibility of using cells grown in vitro to replace heart cells lost during aging and as a result of disease," says study leader Laurie Boyer, associate professor- Professor of biology at MIT.
Dr. Boyer's laboratory studies the organization of DNA and the regulation of gene expression, which makes it possible to create all the diversity of cells that make up the human body.
Inside the cell, DNA is wrapped around proteins called histones, which largely determine which genes are available to reading mechanisms at any given time. Histones can be labeled with various chemical labels that affect the availability of a particular DNA site.
"These modifications cause structural changes that can act as binding sites to other factors," explains Joe Wamstad, a postdoctoral fellow in Dr. Boyer's lab and one of the lead authors of the Cell paper. This can make DNA more or less accessible to the influence of other factors, ensuring that a particular gene is not expressed at an unnecessary time."
Womstad and his colleagues found that histone modification patterns change rapidly during embryonic stem cell differentiation. Moreover, these patterns make it possible to identify genes expressed at various stages of differentiation, as well as regulatory elements controlling these genes.
To establish these patterns, the scientists grew mouse embryonic stem cells and treated them with proteins and growth factors that induce their differentiation into heart cells. In this line of development, four stages can be distinguished – from embryonic stem cells to fully differentiated cardiomyocytes that make up the heart muscle.
Using high-performance sequencing technology, the researchers analyzed histone modification and identified expressed genes at each of the four stages of differentiation.
Comparison of modification patterns with gene activity at a particular time allowed identification of groups of genes with related functions. In addition, regulatory regions located far from the genes controlled by them were identified. Many of these regions are located in areas of DNA that were previously considered "junk". Recent studies have shown that most of the "junk" DNA actually plays an important role in regulating gene expression.
"We are beginning to link genes with regulatory elements that activate them and draw a picture of the molecular network that controls these heart–specific programs and activates them – DNA elements important for the inclusion of all genes necessary for the formation of a heart cell," comments the goals and results of his work Vomstad.
In addition, the researchers identified transcription factors – proteins that initiate gene expression – that apparently work together in regulatory areas, controlling the transcription of genes important for heart development. Defects in many of the transcription factors are associated by scientists with congenital heart defects.
Genome sequencing has already revealed genetic variations that are more common in people with congenital heart defects or cardiovascular diseases. The data obtained in this study should help to understand why these variations lead to such diseases.
In addition, according to Richard Lee, professor of medicine at Harvard Medical School and a researcher at the Harvard Stem Cell Institute, the results obtained can help in the creation of heart cells for use in regenerative medicine.
Currently, scientists are looking for other combinations of transcription factors involved in controlling the differentiation of stem cells into cardiac cells. In addition, they study changes in the regulatory sequences they have identified in order to find out how these sequences lead to congenital heart disease or determine predisposition to age-related cardiovascular diseases.
Portal "Eternal youth" http://vechnayamolodost.ru20.09.2012