Molecular Atlas of the Adult Mouse Brain

Brain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain organization based on unbiased extraction of spatially-defining features. Applying whole-brain spatial transcriptomics, we captured the gene expression signatures to define the spatial organization of molecularly discrete subregions. We found that the molecular code contained sufficiently detailed information to directly deduce the complex spatial organization of the brain. This unsupervised molecular classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and a new division of striatum. The whole-brain molecular atlas further supports the identification of the spatial origin of single neurons using their gene expression profile, and forms the foundation to define a minimal gene set - a brain palette - that is sufficient to spatially annotate the adult brain. In summary, we have established a new molecular atlas to formally define the identity of brain regions, and a molecular code for mapping and targeting of discrete neuroanatomical domains. We hybridized 75 coronal sections from one brain hemisphere of 3 adult mice with Spatial Transcriptomics and defined a molecular atlas using clustering algorithms.脑图谱对于整合信息、解析神经环路与行为的结构-功能关联至关重要。本研究旨在通过无偏提取空间定义特征，对成年小鼠脑的组织结构开展系统性分类。本研究采用全脑空间转录组学（Spatial Transcriptomics）技术，获取基因表达特征以界定分子层面离散亚区的空间排布模式。研究发现，该分子编码蕴含足够精细的信息，可直接推导大脑复杂的空间组织结构。此次无监督分子分类揭示了全新的脑区及皮层分层特异性亚区——例如在新皮层（isocortex）与海马体（hippocampus）中——并发现了纹状体（striatum）的全新分区方式。该全脑分子图谱还可依托单神经元的基因表达谱辅助识别其空间起源，并为定义最小基因集——即“脑调色板（brain palette）”——奠定基础，该基因集足以对成年小鼠脑完成空间注释。综上，本研究构建了全新的分子图谱，可正式界定脑区的身份特征，并建立了用于映射和靶向离散神经解剖学结构域的分子编码体系。本研究将3只成年小鼠单侧大脑半球的75份冠状切片进行空间转录组学（Spatial Transcriptomics）杂交，并通过聚类算法构建了该分子图谱。