We’ve uncovered a master gene that switches on human development

Understanding embryonic development could improve IVF success PHILIPPE PLAILLY/SCIENCE PHOTO LIBRARY We now know the master gene that controls embryonic development in people. Called NANOG, its role has been identified a technique called CRISPR base editing. The discovery might lead to ways to boost the success rate of IVF, among other conditions. “The other reason we study these early stages of human development is that it has really profound importance for stem cell biology,” says Kathy Niakan at the University of Cambridge. “A better understanding will help stem cell research and regenerative medicine, and that could have a transformative impact that can affect all of our lives.” Common IVF test misses some genetic abnormalities in embryos It’s long been known from animal studies that NANOG plays a role in embryonic development. The gene was named after the Celtic world of the ever-young, Tír na nÓg, because its activation is what makes stem cells immortal. Crucially, though, the team’s work shows that NANOG has a different role in people than in other animals, such as mice. When a fertilised egg starts developing, the cells take on one of three different roles – forming the placenta, the yolk sac, which is also in mammalian embryos, or the embryo itself. When the team used base editing to disable NANOG in fertilised mouse eggs, none of the resulting cells developed into yolk sac progenitors. Base editing is a modified form of CRISPR that changes a single DNA letter at a time. By contrast, the original form of CRISPR slices through DNA strands, resulting in various kinds of mutations. “The precision of the technique reduces the likelihood of unintended chromosomal abnormalities, which can occur with the original version,” says Niakan. But when the team disabled NANOG in human eggs donated , none of the cells developed into those that form the embryo. In other words, the activation of NANOG is what initiates the developmental programme that results in cells forming a human body. These embryos still appeared normal under a microscope, however, and the selection of IVF for implantation is based largely on shape, Niakan says. “One out of two times, even though from the shape it looks like the embryo is developing well, it doesn’t have the potential to implant,” she says. “So perhaps , that knowledge could help improve on these rates.” Niakan’s team isn’t the first to base-edit human embryos.