Early mammalian development is a highly complex process involving elaborate and highly coordinated biological processes. One such process is zygotic genome activation (ZGA) which occurs following the union of the sperm and egg, marking the beginning of life. The resultant early embryos, termed ‘zygotes’ are capable of generating the entire organism, a property known as totipotency.

Totipotent cells sit atop the developmental hierarchy and have the greatest potency of all cell types, giving it limitless therapeutic potential. Surpassing pluripotent embryonic stem cells, which are only able to differentiate into all cell types within the embryo, the totipotent zygote loses its totipotency as it matures into pluripotency.

Scientists at the National University of Singapore’s Yong Loo Lin School of Medicine have now found a way to manipulate pluripotent cells into acquiring the totipotent capacity previously thought to exist only in the zygote. This not only provides key insights into how totipotency is formed and the earliest events in mammalian development, but opens new doors for potential cell therapies that were previously unexplored.