Researchers, led by an Indian-origin scientist, have for the first time used human embryonic stem cells to create primordial germ cells that give rise to egg and sperm.
Although this had already been done using rodent stem cells, scientists at the University of Cambridge in UK and the Weizmann Institute in Israel are the first to achieve this feat using human stem cells.
“The creation of primordial germ cells is one of the earliest events during early mammalian development,” said Dr Naoko Irie, first author of the paper from the Wellcome Trust/Cancer Research UK Gurdon Institute at 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.
“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,” said Irie.
Professor Azim Surani at the Gurdon Institute, who led the research, and his colleagues found that a gene known as SOX17 is critical for directing human stem cells to become primordial germ cells (PGCs).
This was a surprise as the mouse equivalent of this gene is not involved in the process, suggesting a key difference between mouse and human development.
The group showed that PGCs could also be made from reprogrammed adult cells, such as skin cells, which will allow investigations on patient-specific cells to advance knowledge of the human germline, infertility and germ cell tumours.
The research also has potential implications for understanding the process of ‘epigenetic’ inheritance.
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.
These methylation patterns can be passed down to the offspring.
Surani and colleagues have shown that during the PGC specification stage, a programme is initiated to erase these methylation patterns, acting as a ‘reset’ switch. However, traces of these patterns might be inherited – it is not yet clear why this might occur.
“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 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,” Surani added.
The study was published in the journal Cell.