Ancient Viral DNA Plays a Key Role in Embryonic Development

More than half of the human genome comprises remnants of ancient viral DNA, known as transposable elements, which are widespread across life forms. Once thought to be "junk" DNA, researchers from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) have uncovered their vital role in early embryonic development.

During the initial hours and days after fertilization, transposable elements—relics of ancient viral infections—reactivate. This reactivation coincides with the remarkable plasticity of embryonic cells, a stage where cells possess the ability to differentiate into any cell type. Despite their importance, the molecular mechanisms and factors governing this process remain poorly understood.

Studies in model organisms like mice suggest that transposable elements are crucial for cellular plasticity. However, whether this principle holds true across all mammals is unclear due to the varied evolutionary histories of these genetic remnants. Understanding the regulatory mechanisms of these elements is essential for advancing reproductive medicine and revealing the basic principles of genome regulation.

To explore this, researchers led by Professor Maria-Elena Torres-Padilla developed a novel technique to study the transcription of these ancient DNA sequences. By analyzing embryos from multiple mammalian species, including mice, cows, pigs, rabbits, and rhesus macaques, they created a comprehensive single-embryo atlas.

Their findings revealed that early mammalian embryos re-express transposable elements previously thought to be extinct. Interestingly, different species express distinct forms of these elements, but the activation of these ancient sequences is conserved across mammals. This discovery sheds light on a shared evolutionary mechanism regulating early development.

Pinpointing specific transposable elements offers new possibilities for gene regulation. These elements provide a way to control thousands of genes simultaneously, paving the way for advancements in stem cell differentiation and cellular reprogramming.

"Our research highlights the importance of understanding the regulatory principles behind transposable elements," said Dr. Marlies Oomen Torres-Padilla, co-first author and professor at Helmholtz Munich. "By leveraging these insights, we can influence cell fate, which is critical for stem cell research and regenerative medicine."

Professor Torres-Padilla also emphasized the broader significance of the findings. “Transposable element activation is a unique feature of early embryos in multiple mammalian species. Understanding how these cells regulate ancient viral elements enhances our grasp of cellular plasticity mechanisms and opens doors to future therapeutic applications.”

This study has generated an unprecedented dataset, offering valuable insights for researchers studying early development across species. While most studies focus on single species like humans or mice, this comparative approach identified regulatory pathways shared across mammals, providing a rich resource for developmental and reproductive biology research.

The findings not only deepen our understanding of early embryo development but also highlight the potential of ancient viral DNA to transform research on gene regulation, cell plasticity, and regenerative medicine.