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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 chromatin differences between different cell types and their potential roles in brain function. Here, we employed single-cells ATAC-seq to generate a chromatin accessibility dataset from 16 adult rat brain regions, obtained 174,593 high-quality nuclei. We identified cell subtypes of two cell types (neuronal and non-neuronal) with highly specific distributions and characterized gene regulatory elements associated with cell type-specific regions. To further investigate the gene regulatory network of spinal cord regeneration process, we integrated our scATAC-seq data with published single- nucleus RNA-seq data of spinal cord, identified more detailed regeneration related elements to drawGRNs centered on the transcription factor Jun in OPC. Simultaneously, we also performed similar integration analysis in midbrain. Our findings provide a solid foundation for comprehensively dissecting the molecular architecture of the mammalian nervous system.

哺乳动物神经系统通过高度特化且相互作用的结构调控复杂生理功能。单细胞测序（single-cell sequencing）可获取细胞类型特异性的染色质结构与调控元件信息，揭示不同细胞类型间的染色质差异及其在脑功能中的潜在作用。本研究采用单细胞ATAC-seq（single-cell ATAC-seq），对16个成年大鼠脑区生成染色质可及性数据集，最终获得174593个高质量细胞核。我们鉴定出神经元与非神经元两类细胞的亚型，其分布具有高度特异性，并表征了与细胞类型特异性区域相关的基因调控元件。为进一步探究脊髓再生过程中的基因调控网络，我们将本研究的scATAC-seq数据与已发表的脊髓单细胞核RNA-seq（single-nucleus RNA-seq）数据进行整合，鉴定出更多与再生相关的精细调控元件，构建以转录因子Jun为核心的少突胶质细胞前体细胞（oligodendrocyte progenitor cell, OPC）基因调控网络（Gene Regulatory Networks, GRNs）。同时，我们在中脑中开展了类似的整合分析。本研究结果为全面解析哺乳动物神经系统的分子架构提供了坚实基础。