A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

The isocortex and hippocampal formation (HPF) in the mammalian brain play critical roles in perception, cognition, emotion and learning. We profiled ~1.3 million cells covering the entire adult mouse isocortex and HPF and derived a transcriptomic celltype taxonomy which includes many new glutamatergic and GABAergic neuron types. Contrary to the traditional view of HPF as having a simpler cellular organization, we discover a complete set of glutamatergic types in HPF homologous to all major subclasses found in the six-layered isocortex, suggesting that HPF and isocortex share a common circuit organization. We also identify large-scale continuous and graded variation of cell types along isocortical depth, across isocortical sheet and in multiple dimensions in hippocampus and subiculum. Overall, our study establishes a molecular architecture of mammalian isocortex and hippocampal formation and begins to shed light on its underlying relationship with the development, evolution, connectivity and function of these two brain structures. Single cell RNA-seq using the 10x genomics and Smart-seq v4 methods. Cells were isolated from mouse cortex and hippocampal formation. The dataset includes 175 10x genomics libraries containing ~1.2 million cells and 73.363 Smart-seq v4 cells.哺乳动物大脑中的新皮层（isocortex）与海马结构（hippocampal formation, HPF）在感知、认知、情感与学习过程中发挥关键作用。本研究对覆盖成年小鼠全脑新皮层与海马结构（HPF）的约130万个细胞开展了单细胞转录组谱分析，并构建了涵盖多种新型谷氨酸能与γ-氨基丁酸能神经元类型的转录组细胞分类体系。与传统认为海马结构（HPF）细胞组织更为简单的观点相悖，我们在HPF中发现了一套完整的谷氨酸能神经元类型，其与六层新皮层中的所有主要亚类具有同源性，这表明HPF与新皮层拥有共通的环路组织模式。我们还观测到细胞类型沿新皮层深度、跨新皮层皮层板，并在海马与海马下托（subiculum）的多个维度上呈现出大规模连续梯度变异。总体而言，本研究构建了哺乳动物新皮层与海马结构的分子架构，并初步阐明了其与这两种脑结构的发育、演化、连接及功能之间的内在关联。本研究采用10x Genomics与Smart-seq v4技术开展单细胞RNA测序。细胞从小鼠皮层与海马结构中分离得到。本数据集包含175个10x Genomics文库（约120万个细胞）与73363个Smart-seq v4测序细胞。