Mammals may have hijacked ancient viruses to master cell fate

Health · Published 18 October 2026 Swipe more like this →

In short: We often think of viruses as mere invaders, but some may have become essential architects of life. New research suggests that placental mammals have co-opted endogenous retroviruses to regulate the very limits of what a cell can become, driving the transition from totipotency to pluripotency.

Cell potency describes a spectrum of developmental potential. At the peak is totipotency, the ability of a single cell—like a zygote or blastomere—to produce every cell type in an organism, including both embryonic tissues and extraembryonic tissues like the placenta. As development progresses, cells typically lose this 'privileged' state. By the time an embryo reaches the blastocyst stage, the inner cell mass becomes pluripotent; these cells can form all body tissues but lack the capacity to create the placenta.

However, researchers have identified a rare, transient population of cells within mouse embryonic stem (ES) and induced pluripotent stem (iPS) cultures that briefly 'revert' to a two-cell-like (2C) state. These 2C-like cells are unique because they lack standard pluripotency proteins like Oct4, Sox2, and Nanog, yet they regain the ability to contribute to extraembryonic tissues. This suggests that cells can cycle in and out of this high-potency state, a process partially governed by histone-modifying enzymes that manage the cell's epigenetic landscape.

The most startling finding is the mechanism behind this shift. Transcriptome sequencing revealed that many of the transcripts required for this 2C-like state are initiated by long terminal repeats derived from endogenous retroviruses. This suggests that placental mammals have effectively hijacked foreign genetic sequences to drive cell-fate regulation. These retroviral elements are not just dormant passengers; they appear to be active drivers of the complex regulatory networks that determine how an embryo organizes itself into a living animal.

This discovery reframes our understanding of evolutionary biology. It suggests that the very mechanisms allowing for complex pregnancy and development in mammals may rely on these ancient, hijacked sequences. By integrating these viral elements into the host's regulatory machinery, evolution has created a sophisticated system for toggling cell potency, moving between the ability to build an entire organism and the specialized instructions needed to build a body.

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