학술논문
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Document Type
Article
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; Tieu, Michael; Torkelson, Amy; Tung, Herman; Valera Cuevas, Nasmil; Vance, Shane; Wadhwani, Katherine; Ward, Katelyn; Levi, Boaz; Farrell, Colin; Young, Rob; Staats, Brian; Wang, Ming-Qiang Michael; Thompson, Carol L.; Mufti, Shoaib; Pagan, Chelsea M.; Kruse, Lauren; Dee, Nick; Sunkin, Susan M.; Esposito, Luke; Hawrylycz, Michael J.; Waters, Jack; Ng, Lydia; Smith, Kimberly; Tasic, Bosiljka; Zhuang, Xiaowei; Zeng, Hongkui
Source
Nature; December 2023, Vol. 624 Issue: 7991 p317-332, 16p
Subject
Language
ISSN
00280836; 14764687
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.