This research from Nature Neuroscience explores how the mammalian central nervous system regulates gene expression following injury. By utilizing single-nucleus multiomics, the authors identified thousands of injury-responsive enhancers (IRENs) that control cell-type-specific repair and stress programs in the mouse spinal cord. They developed deep learning models to decode the complex DNA sequences of these enhancers, revealing how generic stimulus signals combine with specific cell identity programs. The study demonstrates that these decoded sequences can be used to selectively target reactive astrocytes with therapeutic gene delivery vectors. Ultimately, this work provides a blueprint for engineering precision genomic tools to treat disease-associated cell states in the brain and spinal cord.

References:

• Zamboni M, Martínez-Martín A, Rydholm G, et al. The regulatory code of injury-responsive enhancers enables precision cell-state targeting in the CNS[J]. Nature Neuroscience, 2026, 29(2): 337-349.

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