Completing the map of the human genome, back in 2000 and 2003, was a monumental task and a milestone on the road to understanding our genetics. Here’s another milestone: A map that shows in detail how the human genome is modified during embryonic development. Just completed and published by a team of researchers from the Genome Institute of Singapore, IBM Thomas J. Watson Research Center, and Scripps Research Institute, the new study provides the genomic map (a map of genes in human chromosomes) for each of three stages in the development of stem cells from embryonic pluripotent (when the cell can become any other type of cell), to embryonic stem cells partially differentiated into skin cells, and finally into adult (fully differentiated) skin cells.
The underlying targets of these ‘genomic snapshots’ was to map the changes in DNA methylation. Chemically, this is the process whereby a methyl (CH3, related to methane CH4) is attached to genes. In most cases, methylation turns off the gene, that is, suppresses its expression. Once a gene has been methylated, it typically remains that way throughout the life of the cell and is also passed on to any cell created from it. In short, this is how cells become differentiated – how a stem cell becomes a skin cell – various genes are shut down, and the end result is a skin cell.
In reviewing the data produced by the study—information on the methylation of three billion base pairs of DNA—the scientists were able to identify previously unknown patterns of DNA methylation. They identified cases where DNA methylation appeared to enhance, rather than repress, the activity of the surrounding DNA, and found evidence to suggest a role for DNA methylation in the regulation of mRNA splicing.
“We produced a very large amount of data,” said Loring [Scripps Research Professor Jeanne Loring, co-author of the paper], “but it actually simplifies the picture. We identified patterns of many genes that are methylated or de-methylated during differentiation. This will allow us to better understand the exquisitely choreographed changes that cells undergo as they develop into different cell types.”
The data from this study are being made publicly available. For one thing, there is an enormous amount of data, and it will take many researchers many years to work through it. For another, it is usually in collateral studies based on genomic analysis that eventually lead to the most revealing information. This has been the case with the human genome and will be expected for this genome study of stem cell development.