Geneticists Shed Light On Early Human Development
U.S. geneticists say that for the first time ever they have successfully managed to induce human embryonic stem cells to transform into germ cells capable of producing egg and sperm cells “” a discovery that not only illuminates a previously ill-understood phase of human development but one that also carries practical potential for the treatment of infertility.
Dr. Renee Riejo Pera of Stanford University in California explained that getting back to the earliest phases of human life and elucidating their genetic pathways was critical to all future advances in the field.
“We are really trying to look at the origins of normal and abnormal human development by going to the source,” explained Pera in a telephone interview with Reuters.
“For years and years, we haven’t had the ability to look at how germ cells “” the cells that give rise to eggs and sperm “” how they are made, what genes are required, what pathways are active.”
The authors of the study, which will appear in this month’s issue of Nature, explained that this phase of the research had to be conducted with human cells because the genes that come into play are specific to humans and not found in animals.
“Germ cells in humans normally develop between day 12 after fertilization through the first trimester,” said Pera.
“That is a place we can’t look. We can’t see because, obviously, it is in utero,” Pera said.
Pera’s team is confident that their findings will open new paths of research into early human development, eventually shedding light on the transmission of inherited disease and the mechanics of infertility.
University of Kent geneticist Darren Griffin says that the “potential is enormous” for what researchers will be able to do with these newfound insights, noting that them may allow scientists to make headway in understanding secondary factors that may influence fertility, such as environmental pollution.
The team’s breakthrough was made possible when Pera’s colleague, Dr. Kehkooi Kee, discovered an ingenious method of isolating germ cells from embryonic stem cells by inserting a gene that produces green glowing proteins whenever germ cells become active.
Pera explained the elegant simplicity of Dr. Kee’s identification method.
“A green light comes on when a germ cell has been formed. It raises its hand.”
When the researchers were confident that they had located germ cells, they began to systematically activate and deactivate a variety of genes they suspected were key players in the conversion of stem cells to immature germ cells.
Their hunch proved correct.
The team observed that a gene known as DAZL was critical for stimulating embryonic stem cells into germ cells, while two other genes known as DAZ and BOULE were responsible for causing the cells to undergo meiosis “” the process by which cells split their number of chromosomes in half before combining with another cell for fertilization.
Pera explained that some of the sperm cells even went through the entire process of meiosis in vitro, indicating her team had “hit the nail on the head.”
One known cause of infertility in humans is the production of too few germ cells or the production of low quality germ cells.
“We think if there’s immature germ cells that are available in a person, we might be able to use this system to mature them and push them forward into development,” explained Pera, an approach that they hope might also prove useful with induced pluripotent stem cells””adult cells that have been genetically manipulated to act like embryonic stem cells.
The group’s hope is to one day be able to extract cells from people with infertility problems and reprogram them to produce germ cells which could then be used to study what specific factors are causing that person’s infertility. Only a few years ago such method of infertility therapy would have been considered the stuff of scientific fantasy, but as the field of genetic research advances more rapidly than most anyone expected, it seems to have become a question of “when” rather than “if” such technology will be available.
—
On the Net: