美国艾伦脑科学研究所Hongkui Zeng和Zizhen Yao共同合作，近期取得重要工作进展。他们研究绘制了小鼠全脑细胞类型高分辨率转录组和空间图谱。相关研究成果2023年12月13日在线发表于《自然》杂志上。

据介绍，哺乳动物的大脑由数百万至数十亿个细胞组成，这些细胞被组织成许多具有特定空间分布模式、结构和功能特性的细胞类型。

研究人员报道了一个完整的、高分辨率的成年小鼠大脑转录组学和空间细胞类型图谱。细胞类型图谱是通过组合约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）数据集和约430万个细胞的空间转录组数据集使用荧光原位杂交（MERFISH）技术创建的。该图谱按层次划分为4个嵌套的分类级别：34个类、338个子类、1201个超类型和5322个聚类。研究人员提供了一个在线平台Allen Brain Cell Atlas，以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。研究人员系统地分析了整个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同一性和空间特异性之间的高度对应性。

研究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的二分法。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彼此关系更密切的神经元类型。这一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多样性和异质性。最后，研究人员发现转录因子是细胞类型分类的主要决定因素，并确定了一种组合转录因子代码，该代码定义了大脑所有部位的细胞类型。

总之，小鼠全脑转录组学和空间细胞类型图谱为哺乳动物大脑的细胞和电路功能、发育和演化的综合研究奠定了基准参考图谱和基础资源。

附：英文原文

Title: A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

Author: Yao, Zizhen, van Velthoven, Cindy T. J., Kunst, Michael, Zhang, Meng, McMillen, Delissa, Lee, Changkyu, Jung, Won, Goldy, Jeff, Abdelhak, Aliya, Aitken, Matthew, Baker, Katherine, Baker, Pamela, Barkan, Eliza, Bertagnolli, Darren, Bhandiwad, Ashwin, Bielstein, Cameron, Bishwakarma, Prajal, Campos, Jazmin, Carey, Daniel, Casper, Tamara, Chakka, Anish Bhaswanth, Chakrabarty, Rushil, Chavan, Sakshi, Chen, Min, Clark, Michael, Close, Jennie, Crichton, Kirsten, Daniel, Scott, DiValentin, Peter, Dolbeare, Tim, Ellingwood, Lauren, Fiabane, Elysha, Fliss, Timothy, Gee, James, Gerstenberger, James, Glandon, Alexandra, Gloe, Jessica, Gould, Joshua, Gray, James, Guilford, Nathan, Guzman, Junitta, Hirschstein, Daniel, Ho, Windy, Hooper, Marcus, Huang, Mike, Hupp, Madie, Jin, Kelly, Kroll, Matthew, Lathia, Kanan, Leon, Arielle, Li, Su, Long, Brian, Madigan, Zach, Malloy, Jessica, Malone, Jocelin, Maltzer, Zoe, Martin, Naomi, McCue, Rachel, McGinty, Ryan, Mei, Nicholas, Melchor, Jose, Meyerdierks, Emma, Mollenkopf, Tyler, Moonsman, Skyler, Nguyen, Thuc Nghi, Otto, Sven, Pham, Trangthanh, Rimorin, Christine, Ruiz, Augustin, Sanchez, Raymond, Sawyer, Lane, Shapovalova, Nadiya, Shepard, Noah, Slaughterbeck, Cliff, Sulc, Josef

Issue&Volume: 2023-12-13

Abstract: 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 properties1,2,3. 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.

DOI: 10.1038/s41586-023-06812-z

Source: https://www.nature.com/articles/s41586-023-06812-z