New technique maps life's effects on our DNA
Collaborators from the Wellcome Trust Sanger Institute-EBI Single Cell Genomics Centre and the BBSRC-funded Babraham Institute have developed a new approach that reveals how our environments affect our development and the traits we inherit from our parents. The DNA in each of our cells is tagged with chemical markers – known as epigenetic markers – that are added and removed in response to our environment and act as a cellular memory of what has gone before. This technique maps these marks within a single cell, enabling researchers to follow how and why one cell develops to become a skin cell while its neighbour becomes a nerve cell.
Placing epigenetics tags on a cell’s DNA is part of normal development; switching genes on or off to control how the cell develops. Skin cells have a different set of active genes when compared with nerve cells, for example. Environmental factors such as diet can also alter where epigenetic tags are laid on our cells’ DNA and these may affect our long-term health.
“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.
“Epigenetics research has mostly been reliant on using the mouse as a model organism to study early development. Our new single-cell method gives us an unprecedented ability to study epigenetic processes in human early embryonic development, which has been hampered by the very limited amount of tissue available for analysis.”
Dr Gavin Kelsey From the Babraham Institute
The technique, described in Nature Methods, analyses the distribution of one of the key epigenetic marks – DNA methylation – across the whole genome. The cell’s DNA is treated with the chemical bisulphite, amplified and sequenced using high-throughput sequencing machines that are able to detect the location of methylation marks, and analysis reveals which genes are affected.
“Our work provides a proof-of-principle 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. 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.”
Dr Gavin Kelsey At the Babraham Institute
These analyses will help to define how epigenetic changes in individual cells during early development drive cell fate. Current methods look at the methylation of DNA from many different cells within the same tissue. This mixture of cells contain a mixture of differently marked DNA, obscuring those changes that are taking place in an individual cell at the critical moment that its future development is set. By only analysing the DNA of an individual cell, is this new method able to precisely compare one cell to another and has revealed that many of the methylation marks that differ between cells are precisely located in sites that control gene activity.
“This exciting new method has already given some remarkable insights into how much variation there is in the epigenetic information in embryonic stem cells. This may underlie the enormous plasticity these cells have to develop into many different cell types in the body.”
Professor Wolf Reik A founder of the Wellcome Trust Sanger Institute-EBI Single Cell Genomics Centre
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Funding
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council (MRC) and the Wellcome Trust.
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The Babraham Institute
The Babraham Institute, which receives strategic funding (£28.8M 2013-2014) from the Biotechnology and Biological Sciences Research Council (BBSRC), undertakes international quality life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. The Institute’s research provides greater understanding of the biological events that underlie the normal functions of cells and the implication of failure or abnormalities in these processes. Research focuses on signalling and genome regulation, particularly the interplay between the two and how epigenetic signals can influence important physiological adaptations during the lifespan of an organism. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and healthier ageing.
BBSRC
The Biotechnology and Biological Sciences Research Council (BBSRC) invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. Funded by Government, BBSRC invested over £484M in world-class bioscience in 2013-14. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.
The Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
