Newly discovered embryonic cell type that self-destructs to protect the developing embryo

A new quality control system that removes damaged cells from early developing embryos.

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We need to understand much about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the fetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define.

While studying the gene activity data of the early human embryo, scientists discovered an overlooked cell type that self-destructs within days of forming as part of a quality control process to protect the developing fetus. The study offers insights into the early stages of life after fertilization which could, in the future, help improve IVF or regenerative medicine treatments.

A fourth of the cells from 5-day-old embryos did not fit the profile of any of the recognized cell categories (pre-embryo, pre-placenta, etc.), according to the analysis of previously published data on the gene activity of each cell.

Further research revealed that these cells possessed what are known as “Young transposable elements” or “jumping genes.” These rogue DNA components can replicate and re-insert themselves into human DNA, frequently causing harm in the process.

The cells with proteins resulting from the jumping genes were established by staining embryos by project collaborators in Spain.

A little later along in time, the team discovered that their offspring experienced both DNA damage and programmed cell death.

Scientists suggest that this process looks like a form of quality control: selection between cells in favor of the good ones.

Dr. Zsuzsanna Izsvák, co-senior author from the Max Delbrück Center and an expert on mobile DNA, said: “Humans, like all organisms, fight a never-ending game of cat and mouse with these harmful jumping genes.”

“While we try and suppress these jumping genes by any means possible, very early in development, they are active in some cells, probably because we cannot get our genetic defenses in place fast enough.”

Co-lead author Professor Laurence Hurst, from the Milner Centre for Evolution at the University of Bath, said: “If the jumping genes damage a cell – or any other sort of error such as having too few or too many chromosomes – then the embryo is better off removing these cells and not allowing them to become part of the developing baby.

“We are used to natural selection favoring one organism over another. What we see within embryos also looks like survival of the fittest but this time between almost identical cells. We’ve uncovered a novel part of our arsenal against these harmful genetic components.”

Contrarily, the single-cell data revealed that the inner cell mass, ICM, or the crucial cells that will develop into the embryo, do not include jumping genes but express a virus-like gene known as human endogenous virus H. This supports a developing pattern in which we deploy our old genetic foes to battle our new ones, which helps suppress the youthful jumping genes in the inner cell mass.

Scientists noted, “The authors suggest that if the quality control process is too sensitive, the embryo may die. This might explain why some mutations in our system to detect damage in early embryos are also associated with infertility.”

Journal Reference:

  1. Manvendra Singh, Aleksandra M. Kondrashkina et al. A new human embryonic cell type associated with the activity of young transposable elements allows the definition of the inner cell mass. PLOS Biology. DOI: 10.1371/journal.pbio.3002162
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