A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Authors: 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 
Published: December 2023

AbstractThe 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.