The mammalian brain consists of millions to billions of cells that are organized into many cell types with specific spatial distribution patterns and structural and functional properties^1,2,3. Here we report a comprehensive and high-resolution transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The cell-type atlas was created by combining a single-cell RNA-sequencing (scRNA-seq) dataset of around 7 million cells profiled (approximately 4.0 million cells passing quality control), and a spatial transcriptomic dataset of approximately 4.3 million cells using multiplexed error-robust fluorescence in situ hybridization (MERFISH). The atlas is hierarchically organized into 4 nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. We present an online platform, Allen Brain Cell Atlas, to visualize the mouse whole-brain cell-type atlas along with the single-cell RNA-sequencing and MERFISH datasets. We systematically analysed the neuronal and non-neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell-type organization in different brain regions—in particular, a dichotomy between the dorsal and ventral parts of the brain. The dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. Our study also uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types. Finally, we found that transcription factors are major determinants of cell-type classification and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole mouse brain transcriptomic and spatial cell-type atlas establishes a benchmark reference atlas and a foundational resource for integrative investigations of cellular and circuit function, development and evolution of the mammalian brain.

哺乳动物大脑由数百万到数十亿个细胞组成，这些细胞被组织成许多细胞类型，具有特定的空间分布模式以及结构和功能特性^1,2,3 。在这里，我们报告了整个成年小鼠大脑的全面且高分辨率的转录组和空间细胞类型图谱。该细胞类型图谱是通过使用多重分析技术将约 700 万个细胞（约 400 万个细胞通过质量控制）的单细胞 RNA 测序 (scRNA-seq) 数据集与约 430 万个细胞的空间转录组数据集相结合而创建的。抗差错荧光原位杂交（MERFISH）。该图谱按层次结构分为 4 个嵌套分类级别：34 个类、338 个子类、1,201 个超类型和 5,322 个簇。我们推出了一个在线平台 Allen Brain Cell Atlas，用于可视化小鼠全脑细胞类型图谱以及单细胞 RNA 测序和 MERFISH 数据集。我们系统地分析了大脑中的神经元和非神经元细胞类型，并确定了每种细胞类型的转录组身份和空间特异性之间的高度对应性。结果揭示了不同大脑区域细胞类型组织的独特特征，特别是大脑背侧和腹侧部分之间的二分性。背侧部分包含相对较少但高度分化的神经元类型，而腹侧部分包含更多数量的神经元类型，并且彼此关系更密切。我们的研究还揭示了不同细胞类型中神经递质和神经肽表达以及共表达模式的非凡多样性和异质性。 最后，我们发现转录因子是细胞类型分类的主要决定因素，并确定了定义大脑所有部分细胞类型的组合转录因子代码。全小鼠大脑转录组和空间细胞类型图谱为哺乳动物大脑的细胞和电路功能、发育和进化的综合研究建立了基准参考图谱和基础资源。