Scientists create first-ever primordial precursors to sperm, eggs

Chuck Bednar for redOrbit.com – Your Universe Online
For the first time, researchers from the University of Cambridge and the Weizmann Institute in Chiacago have created the precursors to egg and sperm using human stem cells.
While these primordial germ cells had previously been created from rodent stem cells, the new research – which was funded Wellcome Trust and BIRAX (the Britain Israel Research and Academic Exchange Partnership) and is detailed in the latest edition of the journal Cell – marks the first time they have been achieved efficiently using human embryonic stem cells.
As an egg cell is fertilized by a sperm, it begins to divide into a cluster of cells known as a blastocyst, the researchers explained. The blastocyst, which is the earliest stage of the embryo, contains cells that form the inner mass and will become the fetus, as well as some that form the outer wall and will become the placenta.
Cells contained within the inner cell mass are ‘reset’ into stem cells, which allows them to form into any type of cell in the human body. Some of those cells develop into primordial germ cells (PGCs), and they have the potential to become egg or sperm cells (also known as germ cells) later on in life, allowing them to pass on the offspring’s genetic information to its own children.
“The creation of primordial germ cells is one of the earliest events during early mammalian development,” said first author Dr. Naoko Irie of the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge.
“It’s a stage we’ve managed to recreate using stem cells from mice and rats, but until now few researches have done this systematically using human stem cells,” Dr. Irie added. “It has highlighted important differences between embryo development in humans and rodents that may mean findings in mice and rats may not be directly extrapolated to humans.”
Lead investigator Professor M. Azim Surani from the Wellcome Trust Cancer Research UK Gurdon Institute, Dr. Irie and their colleagues discovered that a gene known as SOX17 was essential for coaxing human stem become PCGs. This discovery was described as a surprise, because the mouse equivalent of the gene was not involved in the process at all, suggesting that this is one key difference in the development of rodents and humans.
Previously, scientists had demonstrated that SOX17 was involved in directing stem cells to become endodermal cells, which then develop into cells for the lung, gut and pancreas. However, this marks the first time that it has ever been observed becoming involved in PGC specification.
The researchers demonstrated that PCGs could also be make from reprogrammed adult cells, including skin cells, which will allow them to investigate on patient-specific cells to gain new insights into the human germline, infertility and germ cell tumors.
“The research also has potential implications for understanding the process of ‘epigenetic’ inheritance,” Cambridge University explained. “Scientists have known for some time that our environment – for example, our diet or smoking habits – can affect our genes through a process known as methylation whereby molecules attach themselves to our DNA, acting like dimmer switches to increase or decrease the activity of genes.”
Those methylation patterns can be passed down to the offspring, and Professor Surani’s team has found that during the PGC specification stage, a program is launched that can serve as a type of ‘reset’ switch, erasing these methylation patterns. However, traces of these patterns might be inherited, and it is currently unclear why this could occur, the study authors noted.
“Germ cells are ‘immortal’ in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next,” said Professor Surani. “The comprehensive erasure of epigenetic information ensures that most, if not all, epigenetic mutations are erased, which promotes ‘rejuvenation’ of the lineage and allows it to give rise to endless generations. These mechanisms are of wider interest towards understanding age-related diseases, which in part might be due to cumulative epigenetic mutations.”
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