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  • The Role of Endogenous Retroviruses in Human Development

    Research conducted by the Spanish National Cancer Research Centre (CNIO) has unveiled a critical role of endogenous retroviruses in human embryonic development, as detailed in the journal Science Advances. This study provides an in-depth look at the transition from totipotency to pluripotency in the early stages of embryonic development, a few hours after fertilization.

    From Junk DNA to Essential Genetic Material
    Historically, the genetic remnants of viruses, specifically 'endogenous retroviruses', have been dismissed as 'junk DNA'. However, these viral sequences, constituting 8-10% of the human genome, are now understood to play significant roles. "Intuitively, it was thought that having viruses in the genome could not be good. However, in recent years we are starting to realize that these retroviruses, which have co-evolved with us over millions of years, have important functions, such as regulating other genes. It's an extremely active field of research,” explains Sergio de la Rosa, the first author of the study.

    Discovering a New Role for Endogenous Retroviruses
    The CNIO research, led by Nabil Djouder, delves into the impact of the MERVL endogenous retrovirus during the critical phase when an embryo's cells transition from being totipotent—capable of developing into any cell type—to pluripotent, where they can differentiate into any specialized tissue. "We discovered a new mechanism that explains how an endogenous retrovirus directly controls pluripotency factors," says Djouder.

    The Interplay of MERVL, URI, and Pluripotency
    A pivotal aspect of this research is the discovery of how the MERVL-gag viral protein interacts with the URI gene. Initially, high levels of the MERVL-gag protein inhibit URI's function, maintaining the cells in a totipotent state. As the levels of this viral protein decrease, URI becomes active, facilitating the transition to pluripotency. "It's a smooth transition. When there is a high expression of viral protein, there are fewer pluripotency factors; as ERV expression decreases, URI stabilizes such factors,” elaborates De la Rosa.

    A Symbiotic Evolutionary Relationship
    The study underscores the symbiotic co-evolution of endogenous retroviruses with their host cells, ensuring the precise and timely progression of early embryonic development. The three-way relationship between the viral protein, URI, and pluripotency factors is finely modulated, “to allow sufficient time for the embryo to adjust and coordinate the smooth transition from totipotency to pluripotency and cell lineage specification during embryonic development," stated Djouder.

    This research marks a significant advancement in our understanding of embryonic development and the hidden roles of viral genetic material in our genome, furthering the field of developmental biology and regenerative medicine.

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