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

被引：181

作者：

Yao, Zizhen ^{[1
]}

van Velthoven, Cindy T. J. ^{[1
]}

Kunst, Michael ^{[1
]}

Zhang, Meng ^{[2
]}

Mcmillen, Delissa ^{[1
]}

Lee, Changkyu ^{[1
]}

Jung, Won ^{[2
]}

Goldy, Jeff ^{[1
]}

Abdelhak, Aliya ^{[1
]}

Aitken, Matthew ^{[1
]}

Baker, Katherine ^{[1
]}

Baker, Pamela ^{[1
]}

Barkan, Eliza ^{[1
]}

Bertagnolli, Darren ^{[1
]}

Bhandiwad, Ashwin ^{[1
]}

Bielstein, Cameron ^{[1
]}

Bishwakarma, Prajal ^{[1
]}

Campos, Jazmin ^{[1
]}

Carey, Daniel ^{[1
]}

Casper, Tamara ^{[1
]}

Chakka, Anish Bhaswanth ^{[1
]}

Chakrabarty, Rushil ^{[1
]}

Chavan, Sakshi ^{[1
]}

Chen, Min ^{[3
]}

Clark, Michael ^{[1
]}

Close, Jennie ^{[1
]}

Crichton, Kirsten ^{[1
]}

Daniel, Scott ^{[1
]}

Divalentin, Peter ^{[1
]}

Dolbeare, Tim ^{[1
]}

Ellingwood, Lauren ^{[1
]}

Fiabane, Elysha ^{[1
]}

Fliss, Timothy ^{[1
]}

Gee, James ^{[3
]}

Gerstenberger, James ^{[1
]}

Glandon, Alexandra ^{[1
]}

Gloe, Jessica ^{[1
]}

Gould, Joshua ^{[4
]}

Gray, James ^{[1
]}

Guilford, Nathan ^{[1
]}

Guzman, Junitta ^{[1
]}

Hirschstein, Daniel ^{[1
]}

Ho, Windy ^{[1
]}

Hooper, Marcus ^{[1
]}

Huang, Mike ^{[1
]}

Hupp, Madie ^{[1
]}

Jin, Kelly ^{[1
]}

Kroll, Matthew ^{[1
]}

Lathia, Kanan ^{[1
]}

Leon, Arielle ^{[1
]}

机构：

[1] Allen Inst Brain Sci, Seattle, WA USA

[2] Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Dept Phys, Cambridge, MA 02138 USA

[3] Univ Penn, Philadelphia, PA USA

[4] Proneurotech, San Francisco, CA USA

来源：

NATURE | 2023年 / 624卷 / 7991期

基金：

美国国家卫生研究院;

关键词：

NEURAL STEM-CELLS; CIRCUMVENTRICULAR ORGANS; RESOLVED TRANSCRIPTOMICS; RNA-SEQ; NEURONS; EXPRESSION; IDENTITY; CLASSIFICATION; MIGRATION; FAMILY;

D O I：

10.1038/s41586-023-06812-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 properties(1-3). 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.

引用

页码：317 / 332

页数：52

共 143 条

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