Just as the first clinical trial to be conducted on embryonic stem cells was announced two weeks ago, another report reveals the molecular workings of these complex and controversial cells.
The laboratory of Andrew Feinberg at the School of Medicine recently published a paper in Nature Genetics on the epigenetic markings of embryonic stem cells and their descendent, differentiated cells.
DNA is contained inside most human cells (red blood cells lose their DNA as they mature). Attached to the DNA can be markings, termed epigenetic, which include chemical modifications.
Think of the DNA as text in a book and the epigenetic markings as flags on certain pages that tell "readers" to do specific things at certain DNA sequences.
It has been known for some time that the DNA is compacted differently in embryonic stem cells than it is in its descendent adult stem cells and terminally differentiated cells, the cells that make up muscle, brain and the other tissues of your body.
The epigenetic marks play a crucial role in this different compaction between cell types.
In embryonic stem cells, the DNA is loosely compacted, which allows most genes to be expressed. In differentiated cells, the DNA is tightly compacted and therefore has restricted gene expression.
Depending on the epigenetic marking attached to a DNA sequence, the DNA will be loosely or tightly compacted. One signal for tight packing is adding methyl groups to DNA (a carbon with three hydrogens attached to it).
Feinberg's team found that embryonic cells have very little - only four percent - methylation of its DNA, whereas differentiated tissues like liver and brain have as much as 45 percent of its DNA methylated.
Not only did more DNA get methylated but the size of the regions that were methylated also increased from embryonic to differentiated cells.
Interestingly, but not surprisingly, each cell type has a distinct and specific methylation pattern on its DNA. So the methylated DNA is different in the liver than in the brain. This helps to explain why each cell can have the exact same DNA but be completely different cells with totally different identities.
When the researchers looked at which genes were being expressed in the liver compared to the brain, they found that the genes expressed in the liver were not expressed in the brain and vice versa. And the genes that were not expressed were found in these methylated regions.
Finally, when the researchers looked at cancer they found something surprising. A cancer of the blood system would be expected to have similar DNA methylated patterns to normal cells from the blood system, because the cancer is from that system.
However, the DNA methylation is much less in cancers than in differentiated tissues.
This research raises many interesting questions for stem cell research as well as cancer research.
From this work, the team hopes to propose new models of how the nucleus (where DNA is stored) is organized and its relation to making stem cells and forming cancer.
