Genome editing, OCT4 and human embryo development

UK scientists have used CRISPR-CAS9 to study the role of the OCT4 protein in early human embryo development.

A team of researchers, led by Kathy Niakan from The Francis Crick Institute, London, UK, used genome editing to stop a key gene from producing a protein called OCT4, which normally becomes active in the first few days of human embryo development. After the egg is fertilised, it divides until at about seven days it forms a ball of around 200 cells called the ‘blastocyst’, the researchers said in a press release. The study, published in Nature, found that human embryos need OCT4 to correctly form a blastocyst.

“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 Dr Norah Fogarty from The Francis Crick Institute, first author of the study. “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.”

As well as human embryo development, OCT4 is thought to be important in stem cell biology. ‘Pluripotent’ stem cells can become any other type of cell, and they can be derived from embryos or created from adult cells such as skin cells. Human embryonic stem cells are taken from a part of the developing embryo that has high levels of OCT4. “We have the technology to create and use pluripotent stem cells, which is undoubtedly a fantastic achievement, but we still don’t understand exactly how these cells work,” said Dr James Turner, co-author of the study from the Francis Crick Institute. “Learning more about how different genes cause cells to become and remain pluripotent will help us to produce and use stem cells more reliably.”

Infographic explaining the CRISPR/Cas9 genome editing technique and the stages of human embryo development. Click here to view full-size image. Image courtesy of The Francis Crick Institute.

Dr Kathy Niakan from The Francis Crick Institute, said, “One way to find out what a gene does in the developing embryo is to see what happens when it isn’t working. Now we have demonstrated an efficient way of doing this, we hope that other scientists will use it to find out the roles of other genes. If we knew the key genes that embryos need to develop successfully, we could improve IVF treatments and understand some causes of pregnancy failure. It may take many years to achieve such an understanding — our study is just the first step.”

The team spent over a year optimising their techniques using mouse embryos and human embryonic stem cells before starting work on human embryos. To inactivate OCT4, they used an editing technique called CRISPR/Cas9 to change the DNA of 41 human embryos. After seven days, embryo development was stopped and the embryos were analysed.

The research was led by scientists at the Francis Crick Institute, in collaboration with colleagues at Cambridge University, Oxford University, the Wellcome Trust Sanger Institute, Seoul National University and Bourn Hall Clinic. It was chiefly funded by the UK Medical Research Council, Wellcome and Cancer Research UK.