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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 Bar, 2023. "A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain," Nature, Nature, vol. 624(7991), pages 317-332, December.
  • Handle: RePEc:nat:nature:v:624:y:2023:i:7991:d:10.1038_s41586-023-06812-z
    DOI: 10.1038/s41586-023-06812-z
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    Cited by:

    1. Stefano Nardone & Roberto Luca & Antonino Zito & Nataliya Klymko & Dimitris Nicoloutsopoulos & Oren Amsalem & Cory Brannigan & Jon M. Resch & Christopher L. Jacobs & Deepti Pant & Molly Veregge & Hari, 2024. "A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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