After a spinal cord injury, cells in the brain and spinal cord change to cope with stress and repair tissue. A new study from Karolinska Institutet published in Nature Neuroscience shows that this reaction is controlled by specific DNA sequences. This knowledge could help develop more targeted treatments.
When the central nervous system is damaged, for example in a spinal cord injury, many cells become reactive. This means they activate genes that change function and protect and repair tissues. However, it has long been unclear how this process is regulated.
Researchers at Sweden’s Karolinska Institute are currently mapping thousands of so-called enhancers. A small DNA sequence that acts like a “switch” on a gene, turning it on or increasing its activity. By using an AI model to analyze individual cell nuclei in mice with spinal cord injuries, researchers discovered that these genetic switches are activated after injury and direct specific cell types to respond. The main cells affected were glial cells (supporting cells that help protect and repair the nervous system) such as astrocytes and ependymal cells.
New opportunities for precision treatment
We showed how cells read these instructions through codes that tell them how to respond to injury. This code combines signals from common stressors with the identity of the cell itself. ”
Enric Llorens Bobadilla, Researcher, Department of Cellular and Molecular Biology, Karolinska Institutet
“This opens up the possibility of using the code to specifically target cells affected by damage with therapy,” said Margherita Zamboni, a researcher in the department and lead author of the study.
The study is a collaboration between researchers from Karolinska Institutet and Cylife Lab, and was supported by the European Research Council (ERC), the Swedish Research Council and the Swedish Foundation for Strategic Research. Some researchers have reported consulting roles and patent applications related to the technology.
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Reference magazines:
Zamboni, M., et al. (2025). The regulatory code for damage-responsive enhancers allows precise targeting of cellular states in the CNS. Natural neuroscience. doi: 10.1038/s41593-025-02131-w. https://www.nature.com/articles/s41593-025-02131-w
