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Endogenous retroviruses shape pluripotency specification in mouse embryos.

Sergio de la Rosa1, María Del Mar Rigual1, Pierfrancesco Vargiu2

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Science Advances
|January 24, 2024
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Endogenous retroviruses (ERVs) and MERVL-gag protein regulate embryonic development by controlling pluripotent factors OCT4 and SOX2. This ensures the crucial totipotency-to-pluripotency transition for proper cell formation.

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Area of Science:

  • Developmental Biology
  • Genomics
  • Molecular Biology

Background:

  • Embryonic development involves a critical transition from totipotency to pluripotency.
  • Endogenous retroviruses (ERVs) play essential roles in early development, but their specific functions are unclear.
  • Pluripotent factors like OCT4 and SOX2 are key regulators of cell fate.

Purpose of the Study:

  • To investigate the role of endogenous retroviruses (ERVs) in the totipotency-to-pluripotency transition during mouse embryonic development.
  • To identify specific viral proteins and their interactions with key pluripotency factors.
  • To elucidate the molecular mechanisms by which ERVs influence early lineage specification.

Main Methods:

  • Utilized advanced genetic and biochemical techniques in mouse models.
  • Investigated the function of MERVL-gag, an endogenous retroviral protein.
  • Analyzed the interaction between MERVL-gag, URI protein, and pluripotent factors OCT4 and SOX2.

Main Results:

  • Identified MERVL-gag as a critical regulator of OCT4 and SOX2 during lineage specification.
  • Demonstrated that MERVL-gag functions with URI protein, which is essential for the totipotency-to-pluripotency transition.
  • Showed that loss of URI leads to a stable totipotent state and embryo arrest at the 2-cell (2C) stage.
  • Revealed that URI shields OCT4 and SOX2 from degradation, while MERVL-gag promotes their degradation by displacing URI.

Conclusions:

  • MERVL-gag and URI protein are crucial for the timely progression of early embryonic development.
  • ERVs have coevolved with host cells to ensure proper regulation of pluripotency.
  • The interplay between MERVL-gag, URI, and pluripotent factors is vital for successful embryonic lineage specification.