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单细胞空间转录组揭示猕猴大脑皮层的细胞类型组织。

Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.

机构信息

BGI-Shenzhen, Shenzhen 518103, China; Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark; BGI Research-Southwest, BGI, Chongqing 401329, China; JFL-BGI STOmics Center, Jinfeng Laboratory, Chongqing 401329, China.

Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Cell. 2023 Aug 17;186(17):3726-3743.e24. doi: 10.1016/j.cell.2023.06.009. Epub 2023 Jul 12.

Abstract

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.

摘要

阐明大脑皮层的细胞组织对于理解大脑结构和功能至关重要。我们使用大规模的单细胞 RNA 测序和 143 个猕猴皮质区域的空间转录组分析,获得了 264 种转录本定义的皮质细胞类型的综合图谱,并绘制了它们在整个皮质中的空间分布。我们描述了谷氨酸能、GABA 能和非神经元细胞类型的皮质层和区域偏好,以及细胞类型组成和邻域复杂性的区域差异。值得注意的是,我们发现了各种细胞类型在视觉和体感系统中的区域分布与该区域层次结构之间的关系。来自人类、猕猴和小鼠皮质的转录组数据的跨物种比较进一步揭示了在层 4 中富集的灵长类特异性细胞类型,其标记基因以区域依赖的方式表达。我们的数据为理解灵长类大脑的进化、发育、衰老和发病机制提供了细胞和分子基础。

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