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

Yao, Zizhen and van Velthoven, Cindy T. J. and Kunst, Michael and Zhang, Meng and McMillen, Delissa and Lee, Changkyu and Jung, Won and Goldy, Jeff and Abdelhak, Aliya and Aitken, Matthew and Baker, Katherine and Baker, Pamela and Barkan, Eliza and Bertagnolli, Darren and Bhandiwad, Ashwin and Bielstein, Cameron and Bishwakarma, Prajal and Campos, Jazmin and Carey, Daniel and Casper, Tamara and Chakka, Anish Bhaswanth and Chakrabarty, Rushil and Chavan, Sakshi and Chen, Min and Clark, Michael and Close, Jennie and Crichton, Kirsten and Daniel, Scott and DiValentin, Peter and Dolbeare, Tim and Ellingwood, Lauren and Fiabane, Elysha and Fliss, Timothy and Gee, James and Gerstenberger, James and Glandon, Alexandra and Gloe, Jessica and Gould, Joshua and Gray, James and Guilford, Nathan and Guzman, Junitta and Hirschstein, Daniel and Ho, Windy and Hooper, Marcus and Huang, Mike and Hupp, Madie and Jin, Kelly and Kroll, Matthew and Lathia, Kanan and Leon, Arielle and Li, Su and Long, Brian and Madigan, Zach and Malloy, Jessica and Malone, Jocelin and Maltzer, Zoe and Martin, Naomi and McCue, Rachel and McGinty, Ryan and Mei, Nicholas and Melchor, Jose and Meyerdierks, Emma and Mollenkopf, Tyler and Moonsman, Skyler and Nguyen, Thuc Nghi and Otto, Sven and Pham, Trangthanh and Rimorin, Christine and Ruiz, Augustin and Sanchez, Raymond and Sawyer, Lane and Shapovalova, Nadiya and Shepard, Noah and Slaughterbeck, Cliff and Sulc, Josef and Tieu, Michael and Torkelson, Amy and Tung, Herman and Valera Cuevas, Nasmil and Vance, Shane and Wadhwani, Katherine and Ward, Katelyn and Levi, Boaz and Farrell, Colin and Young, Rob and Staats, Brian and Wang, Ming-Qiang Michael and Thompson, Carol L. and Mufti, Shoaib and Pagan, Chelsea M. and Kruse, Lauren and Dee, Nick and Sunkin, Susan M. and Esposito, Luke and Hawrylycz, Michael J. and Waters, Jack and Ng, Lydia and Smith, Kimberly and Tasic, Bosiljka and Zhuang, Xiaowei and Zeng, Hongkui (2023) A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain. Nature, 624 (7991). pp. 317-332. ISSN 0028-0836

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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.

Item Type: Article
Subjects: Science Global Plos > Geological Science
Depositing User: Unnamed user with email support@science.globalplos.com
Date Deposited: 14 Dec 2023 10:50
Last Modified: 14 Dec 2023 10:50
URI: http://ebooks.manu2sent.com/id/eprint/2382

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