‘Velcro-like’ protein clusters offer fresh insight into stem cell biology

Scientists have uncovered an unexpected mechanism that a key stem cell protein uses to regulate genes.

The study, led by researchers from the University of Edinburgh and the University of Glasgow, suggests that genes can be regulated - not only through chemical signals - but also through the physical organisation and movement of DNA itself.

Embryonic stem cells are the body's ultimate shape-shifters, capable of developing into any tissue. To maintain this flexible, blank-slate state, they rely on a protein called NANOG. Although scientists have known for years that NANOG binds to DNA, exactly how it influences gene activity has remained a mystery.

The research team discovered that NANOG molecules spontaneously assemble into sticky clusters that behave much like the rough side of a Velcro strip. When these rough hooks encounter DNA strands (the soft loop side), they latch on and cross-link multiple strands simultaneously, effectively creating a connected network. This interaction transforms what would otherwise be a fluid mixture of NANOG protein and DNA into a think gel-like material, changing the physical properties of the material.

The team also discovered that the NANOG-DNA network becomes increasingly rigid over time. As the structure ages, it develops a form of ‘mechanical memory’, making the DNA progressively less mobile and potentially helping cells maintain their identity over extended periods.

Rather than acting solely as chemical messengers, proteins such as NANOG may also function as architects of the genome, organizing DNA into structures that influence how genes behave.

The discovery opens a new avenue for understanding stem cell biology and could have implications for regenerative medicine, developmental biology, and diseases in which cellular identity becomes disrupted.