P. Pérez Madrid
Madrid
Updated Wednesday, January 24, 2024-20:00
Health "Whether we like it or not, the history of microbes is also our history"
The evolution of human beings on the planet is linked to
viruses and bacteria
.
Sometimes with better luck than others.
We live with them, they are part of us.
What mark did those who populated the Earth leave us millions of years ago?
A recent study has discovered the key role of an endogenous retrovirus in the formation of embryos.
A working group from the National Cancer Research Center (CNIO) is responsible for the discovery.
The research, published in
Science Advances
, demonstrates that
the virus that infected animals millions of years ago is key today in the development of human life.
The research that is now coming to light
highlights the role of the endogenous retrovirus MERVL
in setting the pace in the development of the embryo, specifically during the specific step of the transition from totipotency to pluripotency, and explains the mechanism by which this happens.
This is what happens a few hours after fertilization: the transition to pluripotency, when the oocyte goes from having two to four cells.
This is going from a cell's ability to generate a complete organism, totipotency, to the ability of a cell to generate different types of tissues and organs.
Hence the importance of
knowing what happens at these key moments to address needs
in the area of
regenerative medicine
and the creation of artificial embryos.
The advance opens a new avenue in the generation of stable cell lines in the totipotency phase.
To know more
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At the moment the discovery has been carried out in mouse models.
"It is a completely new role for endogenous retroviruses," says
Nabil Djouder,
senior author of the work and head of the Growth Factors, Nutrients and Cancer Group at the CNIO, as stated in a statement.
"
We discovered a new mechanism that explains how an endogenous retrovirus controls pluripotency factors directly
."
Along with Djouder,
Sergio de la Rosa
is the first signatory of the publication.
This researcher sought the answer to why when the URI gene is deleted in laboratory animals, the embryos do not even develop.
Djouder's group thoroughly investigates the role of URI.
In humans, this protein is part of a process whose function is to help other proteins adopt the correct folding.
Upon finding the answer, De la Rosa discovered its relationship with the endogenous retrovirus called MERVL.
"Our findings
reveal the symbiotic coevolution of endogenous retroviruses with their host cells,
to ensure smooth and timely progression of early embryonic development," the authors write in the publication.
Nabil Djouder, head of the Growth Factors, Nutrients and Cancer Group at the CNIO.ANTONIO TABERNEROCNIO
In other words, the three-way relationship between the viral protein, URI, and pluripotency factors is very finely modulated, "to give the embryo sufficient time to adjust and coordinate the smooth transition from totipotency to pluripotency, and the specification of the cell lineage during embryonic development," emphasizes Djouder.
How does the virus come to play a role in embryonic development?
The genetic material of the so-called endogenous retroviruses was integrated into the genome of the beings possibly protagonists of the Cambrian explosion, a time more than 500 million years ago when the planet's seas experienced a biodiversity boom.
Over the last decade it has been discovered that the genetic sequences from
these viruses constitute at least 8-10% of the human genome
.
"Until recently,
these viral remains were considered 'junk DNA',
useless or even harmful genetic material," explains De la Rosa.
"Intuitively, it was thought that having viruses in the genome could not be good. But in recent years we are realizing that these retroviruses, which have co-evolved with us over millions of years, fulfill important functions, such as regulating other genes "It is a very active field of research."
The three-way relationship: MERVL virus, URI gene and pluripotency
The results of the CNIO research show that one of the functions of URI is to enable the action of essential molecules to acquire pluripotency;
If URI does not act, neither do the pluripotency factors and the cell is left in a state of totipotency.
Thus, it turns out that
it is a protein of the endogenous retrovirus, MERVL-gag, which in turn modulates the action of URI
.
The scientists find that, throughout the totipotency phase, when there are only two cells in the oocyte, the expression of the viral protein
MERVL-gag
is high;
This protein binds to URI and prevents it from acting.
But little by little the levels change, so that the MERVL-gag viral protein levels drop and URI can come into action: pluripotency appears.
As De la Rosa explains, it is "a smooth transition, when you have a high expression of viral protein, you have fewer pluripotency factors; when the expression of endogenous retroviruses (ERV) decreases, you let URI stabilize those factors."
In the conclusions of the
paper
, the authors state that "the transcriptional burst of endogenous retroviruses during the activation of the zygotic genome could
control the stability of the pluripotent factor
to give the embryo enough time to adjust and coordinate the smooth transition from totipotency to pluripotency." and cell lineage specification during embryo development. ERV activation could constitute
an additional heterogeneous source of developmental potency bias
in the blastomere, playing a key role in cell lineage segregation in the early embryo."
Therefore, they emphasize that "
ERVs have evolved symbiotically with host cells
to finely modulate cellular potency transitions and ensure timely progression and cell lineage specification during early embryo development."