Researchers in the UK have developed a powerful new technique that uses a single cell to map the epigenetic marks that life leaves on our DNA. The development is considered a breakthrough because it will allow scientists to better understand the effect of environment on DNA, such as during the early life of the embryo, and in the development of diseases like cancer.
The team, comprising members from the Babraham Institute – a research center funded by the Biotechnology and Biological Sciences Research Council (BBSRC) – and the Wellcome Trust Sanger Institute, both in Cambridge, reports its findings in the journal Nature Methods.
The fusing of sperm and egg produces a new organism with its own DNA, the fundamental boiler-plate of instructions on how growth and development should unfold. But recently in the history of DNA research, scientists have discovered there is another layer of instructions over the DNA boiler-plate – “epigenetic marks” or chemical tags that annotate the DNA.
Epigenetic marks do not change the underlying DNA sequence, but they add extra instructions that do various things like silence certain genes and switch others on to differentiate a skin cell from a brain cell; they also alter gene behavior according to environmental conditions.
Thus, as well as DNA itself, there is an epigenetic map that acts as a kind of “cellular memory” of a cell’s experience and response to environmental conditions.
This memory is preserved long after the condition in the environment that triggered it has faded. For example, a change in diet might result in a change in the epigenetic map and influence the long-term health of the organism.
Scientists are starting to realize that epigenetics research is as important to understanding health and disease as the study of the underlying DNA. But the tools to do this are not ideal. Researchers have had to rely on using mice as models for human early development, and tissue for analysis is very restricted.
The ability to study the map of all the epigenetic marks of a person by using just a single cell is a significant step forward and gives researchers an “unprecedented ability to study epigenetic processes,” explains corresponding author Dr. Gavin Kelsey, from the Babraham Institute:
“The ability to capture the full map of these epigenetic marks from individual cells will be critical for a full understanding of early embryonic development, cancer progression and aid the development of stem cell therapies.”
The team expects such an application may potentially reduce the number of mice currently used for epigenetic research.
One of the chemical processes that produce epigenetic marks is called DNA methylation, where a methyl tag is attached to the DNA. The method the researchers describe in their paper treats the DNA with bisulfite to locate all the epigenetic methylation marks across the whole genome.
The treated DNA is then amplified and read using high-throughput gene sequencers that show the locations of the methylation marks and the genes affected.
Current methods look for epigenetic marks in groups of cells. This means trying to track what has happened in an individual cell is not clear. The new technique allows researchers to follow what happens in individual cells at a critical time in the early development of an embryo – when each cell has the potential to develop in a unique way.
Using their new technique, the team has already found many of the epigenetic marks that are different between cells are in places that control gene activity.
Dr. Kelsey says the proof-of-principle study shows that “large-scale, single-cell epigenetic analysis is achievable to help us understand how epigenetic changes control embryonic development.”
“The application of single-cell approaches to epigenetic understanding goes far beyond basic biological research,” he adds. “Future clinical applications could include the analysis of individual cancer cells to provide clinicians with the information to tailor treatments, and improvements in fertility treatment by understanding the potential for epigenetic errors in assisted reproduction technologies.”
Funding for the study came from the BBSRC, the Medical Research Council (MRC), the Wellcome Trust, EU Blueprint and EU EpiGeneSys.
Medical News Today also recently learned how Stanford researchers have taken the first step in developing a tool that maps the origin of cancer from biological signatures. The team believes the tool, which traces the origin of certain types of cancer from the biological signature of their mutated cells, will help doctors decide the best treatments for their patients.