Study reveals role of key gene in human embryo development

Study reveals role of key gene in human embryo development

But the latest study highlights key differences between the role of OCT4 in human and in mouse embryos, underscoring the limitations of relying on animal models, says stem-cell scientist Dieter Egli of Columbia University in New York City.

Researchers commonly delete and disable genes in mice, fruit flies, yeast and other laboratory critters to investigate the genes' normal roles, but have never done this before in human embryos.

"One of the most fundamental aspects of becoming human is, how do egg and sperm cells combine to form embryos that develop into a person?"

"This is in a way unexpected, because of the dogma that the earliest stages of development are common for all mammalian and even some non-mammalian species", said Dusko Ilic, reader in stem cell science at King's College London.

The research is controversial as it involves altering "germ line" genes in embryos that could be inherited by future generations.

They found Oct4 appeared to be necessary for an embryo to become a blastocyst, a tiny ball of 200 cells that arises a week after conception and marks a key point in embryonic development.

For the study, the researchers mostly used surplus embryos that had been frozen after in vitro fertilization (IVF) treatments and that couples had donated to research. This could then improve IVF treatments for infertile couples and also help doctors understand why so many pregnancies fail. Only when an embryo successfully reaches the blastocyst stage does it stand any chance of implanting in the womb. To learn about its role in human embryonic development, the researchers used CRISPR-Cas9 to inactivate POU5F1, the gene encoding OCT4, in about 40 embryos.

"It may take many years to achieve such an understanding, our study is just the first step", Niakan said.

Niakan calls her team's work simple research.

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Study reveals role of key gene in human embryo development

The work shows that that "you can do [CRISPR] effectively enough and efficiently enough" to study development, says Janet Rossant, a developmental biologist at The Hospital for Sick Children and the University of Toronto in Canada.

"That tells us that OCT4 is really important for the development of a human blastocyst", Niakan told reporters during a briefing.

It was this sub-set of 10 to 20 cells that went on to produce the foetus and newborn baby after implantation.

"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" says Dr Norah Fogarty from the Francis Crick Institute, first author of the study.

Researchers have traditionally done such studies in mouse embryos, which are more plentiful and carry fewer ethical considerations than human embryos.

The gene they removed makes a protein called OCT4.

Using a "genome editing tool" called "CRISPR/Cas9", her team blocked the formation of the protein that helps days-old embryos form into cell clusters known as blastocysts.

Rob Buckle, chief science officer at Britain's Medical Research Council, praised Niakan's research and findings: "Genome editing technologies - particularly CRISPR-Cas9 used in this study - are having a game-changing effect on our ability to understand the function of critical human genes", he said.