Single-cell chromatin accessibility landscape profiling reveals the diversity of epigenetic regulation in the rat nervous system.

The mammalian nervous system controls complex functions through highly specialized and interacting structures. Single-cell sequencing can provide information on cell-type-specific chromatin structure and regulatory elements, revealing differences in chromatin organization between different cell types and their potential roles of these differences in brain function. Here, we generated a chromatin accessibility dataset through single-cell ATAC-seq of 174,593 high-quality nuclei from 16 adult rat brain regions. We identified cell subtypes of both neuronal and non-neuronal cells with highly specific distributions and characterized gene regulatory elements associated with cell type-specific regions. To further investigate the gene regulatory network involved in spinal cord regeneration, we integrated our scATAC-seq data with published single-nucleus RNA-seq data from the spinal cord, and we identified more detailed regeneration related elements by drawing GRNs centered on the transcription factor Jun in the OPC. We also performed similar integration analyses in the midbrain. Our findings provide a solid foundation for the comprehensive dissection of the molecular architecture of the mammalian nervous system.