A new single-cell bisulfite sequencing (scBS-seq) technique that can advance epigenetic experiments has been developed by researchers from BSRC-funded Babraham Institute and the Wellcome Trust Sanger Institute Single Cell Genomics Centre. Using this powerful technique, all epigenetic marks on the DNA within a single cell can be mapped out. This novel method could enhance our understanding of embryonic development and holds promise for improving clinical applications such as fertility treatments and cancer therapy. It may also reduce the amount of mice used for epigenetic research due to the typical use of the mouse model.
Dr. Gavin Kelsey, from the Babraham Institute, explains the far-reaching benefits this technique can have: “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 restricted by the very limited amount of tissue available for analysis.”
Recently published in Nature Methods, the research describes a novel single-cell technique that can analyze DNA methylation across the entire genome. According to the researchers, “Embryonic stem cells grown in serum or in 2i medium displayed epigenetic heterogeneity, with ‘2i-like’ cells present in serum culture.” They also found that the “integration of 12 individual mouse oocyte datasets largely recapitulated the whole DNA methylome.” This ground-breaking tool holds promise for exploring rare cells and heterogeneous populations and mapping the DNA methylation marks within these samples.
Current methods that are used to observe epigenetic changes use multiple, pooled cells. By looking at a collection of cells, the individual time-sensitive modifications occurring in each particular cell during development and differentiation go unnoticed. The scBS-seq technique has already shown that numerous methylation marks differing between cells are located in areas that have control over gene activity.
Dr. Gavin Kelsey said: “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.”
A founder of the Wellcome Trust Sanger Institute Single Cell Genomics Centre, Professor Wolf Reik, said: “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.”
Source: Learn all about it and read more about their findings here: Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Sébastien A Smallwood, Heather J Lee, Christof Angermueller, Felix Krueger, Heba Saadeh, Julian Peat, Simon R Andrews, Oliver Stegle, Wolf Reik & Gavin Kelsey. April 2014.
References: Science Daily. New technique maps life’s effects on our DNA: Powerful single-cell technique to study environmental effects on DNA. July 2014.