Let’s describe this research backwards – from (potential) result to experiment. One of the most important areas of stem cell research involves how to make stem cells, bypassing the need for extracting and maintaining (controversial) embryonic stem cell lines. So far there have been two approaches. One way is to introduce adult cell nuclei into an egg. The egg contains factors that wipe away all the adult cell markers (epigenetic markers that define what a cell should be – how its genes are expressed). This results in a stem cell, but involves the ethical issues of using live eggs. Another way is to get adult cells to express critical stem cell factors, thus forcing them back to a stem cell state. However, this approach requires using retroviruses to force the gene expression – retroviruses that can potentially cause cancer. What if there is another way?
The approach used by researchers at the University of North Carolina, School of Medicine began with searching for a specific protein complex that is responsible for removing the epigenetic markers from male (sperm) cells. Epigenetic markers are also proteins, created by DNA/RNA but separate from the genetic material. They accompany the genetic material like chemical tags on the genomes of each cell and help determine when and how the genes are expressed. By experimenting with the process of removing epigenetic markers, called DNA demethylation, the researchers eventually isolated a particular protein – elongator, which is required for demethylation when the egg strips epigenetic markers from the sperm.
“The implications of such research have always been clear, and that is why for years researchers have tried to identify a factor responsible for erasing these epigenetic markers,” said senior author Yi Zhang, Ph.D., Howard Hughes Medical Institute Investigator and Kenan Distinguished Professor of biochemistry and biophysics at UNC.
“Many of the genes that are active in stem cells are not active in adult cells because they are methylated. If elongator can catalyze global demethylation, it could be the critical ingredient to these reprogramming cocktails, enabling us to generate stem cells quickly and safely.”
[Source: Cell News]
The findings on the role of the elongator protein complex are significant, but incomplete. Zhang and his team are actively pursuing more detailed knowledge of the structure and composition of elongator, while also experimenting with its use in creating stem cells from adult cells. This is to say that while the research may lead to a third way of producing stem cells, there’s a longish road ahead before the process is reasonably well understood and can be successfully applied to real-world requirements.