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

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

Nature, 2023, vol. 624, issue 7991, 317-332

Abstract: 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 properties1–3. 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.

Date: 2023
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DOI: 10.1038/s41586-023-06812-z

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