美国博德研究所Evan Z. Macosko等研究人员合作揭示成年小鼠大脑的分子细胞结构。这一研究成果于2023年12月13日在线发表在国际学术期刊《自然》上。

为了构建每个大脑结构中细胞类型的综合图谱，研究人员将高通量单核RNA测序与Slide-seq（一种最近开发的空间转录组学方法，具有近细胞分辨率）配对，横跨整个小鼠大脑。这些数据集的整合揭示了每个神经解剖结构的细胞类型组成。研究发现，中脑、后脑和下丘脑的细胞类型多样性非常高，大多数细胞集群需要结合至少三种离散基因表达标记物才能独特定义。

利用这些数据，研究人员开发了一个从遗传学角度访问每种细胞类型的框架，全面描述了神经肽和神经递质信号的特征，阐明了活动调节基因表达的特异性区域特化，并确定了神经和精神表型的遗传性富集。这些数据以在线资源（www.BrainCellData.org）的形式提供，应该能在神经科学领域得到广泛应用，包括构建新的遗传工具以及在脑部疾病研究中优先考虑特定细胞类型和回路。

据了解，哺乳动物大脑的功能依赖于各种特化细胞类型的特化和空间定位。然而，这些细胞类型的分子特征及其在各个解剖结构中的位置仍不完全清楚。

附：英文原文

Title: The molecular cytoarchitecture of the adult mouse brain

Author: Langlieb, Jonah, Sachdev, Nina S., Balderrama, Karol S., Nadaf, Naeem M., Raj, Mukund, Murray, Evan, Webber, James T., Vanderburg, Charles, Gazestani, Vahid, Tward, Daniel, Mezias, Chris, Li, Xu, Flowers, Katelyn, Cable, Dylan M., Norton, Tabitha, Mitra, Partha, Chen, Fei, Macosko, Evan Z.

Issue&Volume: 2023-12-13

Abstract: The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2—a recently developed spatial transcriptomics method with near-cellular resolution—across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource (www.BrainCellData.org), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.

DOI: 10.1038/s41586-023-06818-7

Source: https://www.nature.com/articles/s41586-023-06818-7