RT Journal Article
SR Electronic
T1 A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.03.06.531121
DO 10.1101/2023.03.06.531121
A1 Zizhen Yao
A1 Cindy T. J. van Velthoven
A1 Michael Kunst
A1 Meng Zhang
A1 Delissa McMillen
A1 Changkyu Lee
A1 Won Jung
A1 Jeff Goldy
A1 Aliya Abdelhak
A1 Pamela Baker
A1 Eliza Barkan
A1 Darren Bertagnolli
A1 Jazmin Campos
A1 Daniel Carey
A1 Tamara Casper
A1 Anish Bhaswanth Chakka
A1 Rushil Chakrabarty
A1 Sakshi Chavan
A1 Min Chen
A1 Michael Clark
A1 Jennie Close
A1 Kirsten Crichton
A1 Scott Daniel
A1 Tim Dolbeare
A1 Lauren Ellingwood
A1 James Gee
A1 Alexandra Glandon
A1 Jessica Gloe
A1 Joshua Gould
A1 James Gray
A1 Nathan Guilford
A1 Junitta Guzman
A1 Daniel Hirschstein
A1 Windy Ho
A1 Kelly Jin
A1 Matthew Kroll
A1 Kanan Lathia
A1 Arielle Leon
A1 Brian Long
A1 Zoe Maltzer
A1 Naomi Martin
A1 Rachel McCue
A1 Emma Meyerdierks
A1 Thuc Nghi Nguyen
A1 Trangthanh Pham
A1 Christine Rimorin
A1 Augustin Ruiz
A1 Nadiya Shapovalova
A1 Cliff Slaughterbeck
A1 Josef Sulc
A1 Michael Tieu
A1 Amy Torkelson
A1 Herman Tung
A1 Nasmil Valera Cuevas
A1 Katherine Wadhwani
A1 Katelyn Ward
A1 Boaz Levi
A1 Colin Farrell
A1 Carol L. Thompson
A1 Shoaib Mufti
A1 Chelsea M. Pagan
A1 Lauren Kruse
A1 Nick Dee
A1 Susan M. Sunkin
A1 Luke Esposito
A1 Michael J. Hawrylycz
A1 Jack Waters
A1 Lydia Ng
A1 Kimberly A. Smith
A1 Bosiljka Tasic
A1 Xiaowei Zhuang
A1 Hongkui Zeng
YR 2023
UL http://biorxiv.org/content/early/2023/03/06/2023.03.06.531121.abstract
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.