A joint Israeli-British group today announced a breakthrough in reverting adult cells into primordial human germ cells in the lab – in other words, into the embryonic cells that give rise to sperm and ova.
This is the first time that human cells have been programmed to "go back in time" into this early developmental stage, say the scientists.
The work of turning back the clock on the adult cells was done by groups at the Weizmann Institute of Science and Cambridge University
Their study, which was published today in Cell, could help shed light on fertility problems and early stages of embryonic development.
The real "primordial germ cells" form at an early stage of embryonic development. A fetus, as is known, develops from a single cell (called a zygote) created by the fusion of the mother's egg and the father's sperm. The zygote splits into two identical ones, which each split into two identical ones, until cellular differentiation begins in the next stage, which is when the germ cells – from which sperm and ova arise - are created.
Once differentiation begins, it doesn't go backwards, which scientists have found irksome. “Researchers have been attempting to create human primordial germ cells in the petri dish for years,” says Dr. Jacob Hanna of the Institute’s Molecular Genetics Department, who led the study together with research student Leehee Weinberger.
Efforts to send adult cells back in time, as it were, really took off with the 2006 development of induced pluripotent stem (iPS) cells – adult cells whose development had been reversed, so they looked and acted like embryonic stem cells, and could then theoretically differentiate into any cell type.
That involved Japanese scientists working on mouse cells, but efforts to do the same with human cells failed. This has been the first such endeavor that worked, says the team, following research on how murine and human induced pluripotent stem cells differed.
For reasons unknown, mouse embryonic cells can easily be kept in their stem cell state in the lab. Human induced pluripotent stem cells tend to differentiate.
Hanna and the team created a method to subdue the genetic mechanism responsible for this differentiation, creating a human stem cell that was more like the mouse one – and indeed, did manage to induce these to differentiate into what certainly appears to be primordial germ cells.
Together with the lab group of Prof. Azim Surani of Cambridge University, the scientists further tested and refined the method jointly in both labs.
So will science be able to start from adult cells that undergo reversion, and make sperm and ova in test tubes? Not any time soon; Hanna says primordial germ cells are only the first step in that endeavor. But one day he feels it could be doable, which theoretically could enable women who have undergone chemotherapy or premature menopause to conceive.
In the meantime, the study has already yielded some interesting results. It discovered a gene called Sox17 that directs the human stem cell to differentiate into a primordial germ cell. This doesn't exist in mice.