Genome editing reveals a role for OCT4 in human embryogenesis

Scientists in Britain have snipped a "master gene" out of human embryos in an experiment that could lead to better fertility treatments and galvanise stem cell medicine.

Dr Kathy Niakan led the research at the Francis Crick Institute in London. A £650m biomedical research base opened previous year in London. "We could maybe use a test of the protein that the embryos secrete into the media, and not manipulate the embryos at all, to increase IVF clinical rates", says Niakan.

Kathy Niakan and his team said the United Kingdom has a competitive edge in human embryology because the country has a supportive regulatory framework, as well as public and charitable agencies prepared to fund research in the field. The study could also be helpful for improving in vitro fertilization (IVF) technology. The embryos were redesigned shortly after fertilisation and allowed to develop for seven days. This knowledge can be used to improve IVF treatment and improve our understanding of how some pregnancies fail. The first few steps on that journey are hard to understand.

"If we are to truly understand human embryonic development and improve human health, we need to work directly on human embryos", he says. In the current study, for example, it's clear that Oct4 is an important gene for helping human embryos develop normally. Dusko Ilic, a reader in stem cell science at King's College London, told The Guardian that this research contradicts the thought that experiments in mammalian species can always be extrapolated to humans.

OCT4 normally becomes active in the first few days of embryo development. "Knowing which genes and the pathways they control will be key to all of this".

The latest work switches the spotlight to the basic biological sequence that plays out as a fertilised egg turns into a ball of cells, known as a blastocyst, during the first seven days of development. "Other research methods, including studies in mice, suggested a later and more focused role for OCT4, so our results highlight the need for human embryo research". Not only did the blastocyst not form in the majority of embryos that had CRISPR editing, but there were also differences in the placenta-related cells, as well. "That role is so different from what we would have predicted that it's a super exciting part of the research for me", she says.

It is the first time that researchers have carried out this pioneering procedure to reach a deeper understanding of the earliest stages of human life.

Dr Kay Elder, the study co-author from the Bourn Hall Clinic, has said: "Successful IVF treatment is crucially dependent on culture systems that provide an optimal environment for healthy embryo development".

"We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role", said Norah Fogarty of the Francis Crick Institute, first author of the study, which was published Wednesday in the journal Nature.

In both cases, the embryos did not develop into fetuses and it still may be a while off before such studies allow it. CRISPR and gene editing technology is extremely controversial, with protesters calling it "playing God" or creating "designer babies".


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