Study reveals role of key gene in human embryo development

Scientists use gene-editing technology to knock out genes in human embryos for first time

Niakan's group focused on a gene called OCT4 (also known as POU5F1), a master regulator of gene activity, which is important in mouse embryo development.

This is the first time CRISPR techniques have been used to study how human embryos develop, and the researchers say their study shows how it can be useful.

Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development...

Stopping a gene from working and exploring what happens when it's gone is a good way to find out the gene's goal.

"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.

The study, published in the journal Nature, found Oct4 appeared to be necessary for an embryo to become a blastocyst, a tiny ball of 200 cells that develops a week after conception and marks a key point in embryonic growth. Without it, the blastocyst can not form or develop normally.

Lead author Kathy Niakan (Francis Crick Institute, London) says she hopes the technique can be used by others to identify a whole host of genetic factors that affect pregnancy, but are now poorly understood: "One way to find out what a gene does in the developing embryo is to see what happens when it isn't working". 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.

The scientists discovered a gene called Oct4 is vital to the successful development of an embryo after fertilisation, and without it, a viable pregnancy is highly unlikely. "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. "In mice, (the gene) just maintains the integrity of the embryo". "Of the ones that do, only about 50% will implant, and we don't know why". These were the result of in vitro fertilization (IVF) treatments generated in fertility clinics. "Now we have demonstrated an efficient way of doing this", said Kathy Niakan, one of the Francis Crick Institute authors.

"It may take many years to achieve such an understanding, our study is just the first step". The first few steps on that journey are hard to understand.

The study, which marks a first for the United Kingdom, could help uncover the cause of recurrent miscarriages and lead to more effective fertility treatments.

Researchers usually conduct such studies on mice embryos.

Other experts welcomed the study findings. When inhibited, it prevented the formation of a "blastocyst", which is basically the outer shell of the embryo.

The controversy surrounding gene editing in human embryos partly stems from concern the changes CRISPR makes in DNA can be passed down to the offspring of the embryos, from generation to generation. "This paper opens up a new era of human functional genetics".

It is controversial because, say critics, it evokes a future in which humans can order "designer" babies with specific features, perhaps even intelligence.

Niakan says this study could eventually lead to improvements in the development and therapeutic use of stem cells and in IVF treatment. "Knowing which genes and the pathways they control will be key to all of this".

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