The human egg's ability to transform into a new life, or into new cells that may someday save lives, is well documented. The mystery lies in the mechanics - in how a single cell can transform so nimbly.
Scientists at Michigan State University report this week in the Proceedings of the National Academy of Sciences that they have identified genes unique to the human egg. The identification opens the way to understanding these genes' functions, which may lead to solving problems from infertility to degenerative diseases.
"What's in the egg to have that power?" asked Jose Cibelli, MSU professor of physiology and animal science. "Some of those genes are responsible for the magic trick that the egg has. This paper takes a peek at what genes are in the egg waiting to make these changes."
Combined with sperm, the egg divides and organizes cells to ultimately create a human being.
Combined with technology, the unfertilized egg might be coaxed to produce other specific cells, including stem cells, which can be directed to grow into new tissue. This potential could be used to combat diseases.
Cibelli said his team's mission is to grow stem cells without using fertilized embryos, which can be controversial. This work used only unfertilized human eggs that were obtained from women seeking fertility treatment at a clinic in Santiago, Chile. Women at the clinic must be reproductively healthy, no older than 35, and the cause of infertility must lie within the man. This presented the availability of exceptionally healthy eggs, Cibelli said. All the donors granted informed consent for their surplus eggs to be used for this research.
Cibelli worked with researchers in Chile to extract the RNA from the unfertilized eggs soon after they were harvested. That material (a treasure of genetic information,) was frozen and shipped to MSU.
Cibelli's team, Arif Murat Kocabas, Pablo Ross, Zeki Beyhan and Robert Halgren, started analyzing the thousands of genes represented in the human egg to identify those which are unique to the egg. They teamed with Beth Israel Deaconess Medical Center at Harvard Medical School in Boston to work with sophisticated bioinformatics software.
To make a comparison that would show which genes were uniquely active in the human egg, they used RNA of all parts of the human body - except that of the ovaries, where eggs are produced.
Then the computer analysis began. In a highly sophisticated game of match, every gene in the egg that was found in other tissues was eliminated, so that only unique genes remained.
Cibelli said that the team identified 5,331 human genes that are overexpressed in the egg. Of those, 1,430 are mysteries - their function unknown.
The group also compared the human egg genes with those of a mouse as well as human and mouse embryonic stem cells. On the final intersection, 66 genes were found to be common between the four sets of data.
"There are thousands of genes that are redundant. We found about one in a thousand genes that are unique to the eggs - and some of them, they don't have a known function yet," Cibelli said. "Now we can clone these genes and put them into cells and see if they may have a role in the creation of stem cells - without fertilization or destruction of human embryos."
Cibelli believes some of those genes know the big secrets - such as when a cell should slow down and later become a cell that can grow into any cell of the human body. The computer work of this preliminary search will give way to further experiments.
This research was funded by the MSU Office of the Vice President for Research and Graduate Studies, and supported by the Michigan Agricultural Experiment Station.
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