PT  - JOURNAL ARTICLE
AU  - Zizhen Yao
AU  - Cindy T. J. van Velthoven
AU  - Michael Kunst
AU  - Meng Zhang
AU  - Delissa McMillen
AU  - Changkyu Lee
AU  - Won Jung
AU  - Jeff Goldy
AU  - Aliya Abdelhak
AU  - Pamela Baker
AU  - Eliza Barkan
AU  - Darren Bertagnolli
AU  - Jazmin Campos
AU  - Daniel Carey
AU  - Tamara Casper
AU  - Anish Bhaswanth Chakka
AU  - Rushil Chakrabarty
AU  - Sakshi Chavan
AU  - Min Chen
AU  - Michael Clark
AU  - Jennie Close
AU  - Kirsten Crichton
AU  - Scott Daniel
AU  - Tim Dolbeare
AU  - Lauren Ellingwood
AU  - James Gee
AU  - Alexandra Glandon
AU  - Jessica Gloe
AU  - Joshua Gould
AU  - James Gray
AU  - Nathan Guilford
AU  - Junitta Guzman
AU  - Daniel Hirschstein
AU  - Windy Ho
AU  - Kelly Jin
AU  - Matthew Kroll
AU  - Kanan Lathia
AU  - Arielle Leon
AU  - Brian Long
AU  - Zoe Maltzer
AU  - Naomi Martin
AU  - Rachel McCue
AU  - Emma Meyerdierks
AU  - Thuc Nghi Nguyen
AU  - Trangthanh Pham
AU  - Christine Rimorin
AU  - Augustin Ruiz
AU  - Nadiya Shapovalova
AU  - Cliff Slaughterbeck
AU  - Josef Sulc
AU  - Michael Tieu
AU  - Amy Torkelson
AU  - Herman Tung
AU  - Nasmil Valera Cuevas
AU  - Katherine Wadhwani
AU  - Katelyn Ward
AU  - Boaz Levi
AU  - Colin Farrell
AU  - Carol L. Thompson
AU  - Shoaib Mufti
AU  - Chelsea M. Pagan
AU  - Lauren Kruse
AU  - Nick Dee
AU  - Susan M. Sunkin
AU  - Luke Esposito
AU  - Michael J. Hawrylycz
AU  - Jack Waters
AU  - Lydia Ng
AU  - Kimberly A. Smith
AU  - Bosiljka Tasic
AU  - Xiaowei Zhuang
AU  - Hongkui Zeng
TI  - A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
AID  - 10.1101/2023.03.06.531121
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.03.06.531121
4099  - http://biorxiv.org/content/early/2023/03/06/2023.03.06.531121.short
4100  - http://biorxiv.org/content/early/2023/03/06/2023.03.06.531121.full
AB  - The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. 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 based on the combination of two single-cell-level, whole-brain-scale datasets: a single- cell RNA-sequencing (scRNA-seq) dataset of ∼7 million cells profiled, and a spatially resolved transcriptomic dataset of ∼4.3 million cells using MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes and 5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature 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. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate a myriad of modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain 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 deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.Competing Interest StatementX.Z. is a co-founder and consultant of Vizgen.