A single-cell transcriptomic dataset profiling traumatic brain injury and NeuroD1-based gene therapy in mice.

Traumatic brain injury (TBI), a leading cause of death and disability globally, often results in functional impairments due to complex pathological mechanisms and limited therapeutic options. Recently, astrocytes, the most abundant glia in the central nervous system, have been recognized as therapeutic targets for TBI due to their roles in neuroinflammation and neuroprotection. While NeuroD1-based gene therapy demonstrates therapeutic potential by reversing glial scar, suppressing neuroinflammation, and repairing brain tissue, the underlying mechanisms remain incompletely understood. To elucidate the molecular and cellular mechanisms involved, we conducted single-cell RNA sequencing using cortical stab injury mice of TBI to compare the effects of vehicle treatment with those of NeuroD1-based gene therapy. Single-cell RNA sequencing reveals significant shifts in cellular composition and astrocyte subtypes. These changes involve upregulated synaptic assembly and myelination pathways alongside downregulated mitochondrial and metabolic functions in TBI mice. Conversely, NeuroD1-based gene therapy restores mitochondrial and metabolic functions and attenuates aberrant synaptic and myelination processes. This single-cell transcriptomic dataset provided a valuable resource for mechanistic and therapeutic research for TBI.