Cancer can mimic a gene mutation in early embryos

When an embryo is formed, its genes – provided by the sperm and egg – are silenced. Somehow, early in development, the embryo’s genes must be turned on. Without this important ‘genetic’ switch in the womb, none of us would exist, yet surprisingly little is known about what the switch looks like, or what the information is. they are the ‘molecular finger’ that flips the switch.

Thanks to research published today in Cell Reports, however, embryologists have already described the change and can reveal who the pusher is. The study was a collaborative effort between biologists at the University of Bath, Cambridge University and colleagues in Germany and the US.

The team made the discovery in mice by combining the latest method of sperm implantation with the latest methods of messenger RNA (mRNA) sequencing.

mRNA is the genetic ‘middle man’ that reads information from the genes and carries it to the places in the cell where proteins (things of life) are made. mRNA is produced in eggs before fertilization but also in embryos when the genome has been opened: the researchers were able to distinguish between the two types and identify the change in the embryo ‘on’.

Their method showed how the genes work at the right time after contact with the new eggs. It was found that in the eggs of mice, the process begins within four hours after the sperm injection and follows a program: genes do not change randomly, but in order preset.

The team identified the gene sequence in this pre-set sequence of a single-cell embryo for the first time in any species – and showed that the functions of the functional genes corresponded to the features of early fetal development.

Scientists have worked in many cases to determine which ‘molecular fingerprints’ modify which genes, and because of this, the authors of the new study were able to predict which fingerprints were responsible for early embryonic development: the fingers of others were present. the embryo’s genes, which allow fingerprints to be identified.

Surprisingly, this detective work showed that many of the suspected causes were also linked to cancer.

“Many factors responsible for gene activation in embryos have long been known as major oncogenes,” said Professor Tony Perry who led the research from the Department of Life Sciences in Bath. He added: “Maybe, carcinogeneis recapitulates embryogenesis.”

The team followed up their detective work by showing that suspicious substances (‘molecular fingerprints’) were present in single-cell embryos, inheriting the eggs. When they stopped the factors from working by using inhibitors that block their activity after fertilization, the eggs stopped growing almost immediately.

The researchers continued with one molecular fingerprint – a cancer-related factor called c-Myc. If c-Myc was indeed responsible for changing genes early in development, the team reasoned that blocking it should prevent the change. That’s what they found: without the activity of c-Myc, many genes were not turned on, indicating that c-Myc is a molecular fingerprint that changes the genes of the embryo.

The team suggests that c-Myc and other factors lie dormant in eggs until they are also activated by fertilization. This work in mice overlaps with findings recently published by researchers that show gene activation in human eggs also begins at the single-cell stage.

“Most of the genes that have been changed from entering mice and human one-cell embryos are the same,” said Dr Maki Asami, also from Bath and lead author of the work. “Involvement of the same oncogenic transcription factor is predicted in two models.”

It therefore appears that the findings of this study not only shed light on the mechanisms that control the initiation of mammalian development but also promise to set the stage for game-changing cancer-causing processes, which are often difficult and complex. unknown.

“Our work could open a new chapter in medicine for early cancer detection,” said Professor Perry.

He added that he hopes to follow the instructions given by the detectives of that group so that in the future the comparison between embryos and cancer can be used to prevent cracks in the understanding of both of us.

Reference: Asami M, Lam BYH, Hoffmann M, et al. A program for sequencing genes in single-cell embryos. Cell Rep. 2023;42(2). doi: 10.1016/j.celrep.2023.112023

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