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Human embryo gene expression starts at one-cell stage

10 January 2022
Appeared in BioNews 1127

A new study shows that embryos begin to show gene expression when they are just at the single-cell stage, right after fertilisation

Previous investigations could only detect genetic transcription activity once the embryo had grown to four or eight cells, around two or three days after fertilisation. 

'This is the first good look at the beginning of a biological process that we all go through – the transit through the one-cell embryo stage,' said Professor Tony Perry, one of the researchers who led the study, at the University of Bath.

A team of scientists, co-led by Professor Perry, Dr Giles Yeo at the University of Cambridge and Dr Matthew VerMilyea at Ovation Fertility in the USA, used high-resolution single-cell RNA sequencing to measure genetic transcription in 12 human egg cells provided by seven donors and 12 human embryos provided by six different donors.  

Conversely, the team found reduced gene expression in embryos that did not go on to develop healthily, such as those fertilised by two sperm cells, suggesting that this early genetic activity is essential for successful development. 'Without genome awakening, development fails, so it's a fundamental step.' Professor Perry continued. 

The team found that while the genes expressed in the single-cell embryo continued to be expressed at the two, four and eight-cell stages, their activity was substantially diminished by eight-cell stage. 'It looks as if there is a sort of genetic shift-work in early embryos: the first shift starts soon after fertilisation, in one-cell embryos, and a second shift takes over at the eight-cell stage,' said Professor Perry.

Their findings may lead to a better understanding of what triggers the activation of transcription, something that is not well-understood. 'Although the trigger for activation is thought to come from the egg, it's not known how; now we know which genes are involved, we can locate their addresses and use molecular techniques to find out,' said Professor Perry.

Some factors involved in the activation process are also associated with cancer, suggesting that they may be responsible for triggering the activity in healthy embryos, while abnormalities could later manifest as a risk of cancer. It is also possible that epigenetic traits, may be passed from parent to child at this early stage, by altering the gene activation after fertilisation.

'If true, we should be able to see this altered gene activation signature at the one-cell stage,' Dr Yeo suggested.

The research was published in the journal Cell Stem Cell.

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Human embryonic genome activation initiates at the one-cell stage
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