A pressure lasting a few milliseconds helps skin cells transform into nerve cells.
Yet a skin cell and a neuron have little in common. One protects our body, while the other transmits messages in the brain. But they possess almost the same DNA. What changes is the part of these instructions that each cell uses.
For several years, researchers have known how to act on these instructions to change a cell's function. The problem is that some are difficult to reach. DNA is tightly packed inside the nucleus, and the genes needed for the transformation sometimes remain inaccessible to the tools used in the laboratory.
A team from the University of California, Los Angeles, tried an unexpectedly simple approach: passing mouse skin cells through microscopic channels narrower than their nuclei. For a few milliseconds, the nucleus is compressed. The DNA temporarily loosens as a result.
The researchers combined this pressure with a tool called CRISPRa. Unlike techniques that cut DNA to modify it, CRISPRa is used to activate genes that are already present. It can thus trigger instructions that encourage a skin cell to adopt the characteristics of a neuron.
With CRISPRa alone, about 3% of the cells became neuronal cells. When compression was added, this proportion reached about 10%. The team then prepared the cells by activating another gene, which makes them easier to transform, before starting the conversion. The rate then rose to nearly 40%.
Why seek to make neurons in this way? Human nerve cells are difficult to collect. Producing them in the laboratory could help study certain brain diseases and test new drugs without needing to collect tissue directly from the brain.
For now, the experiment involves mouse cells grown in the laboratory. The researchers will now need to test the method on other cell types, particularly human cells.