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Molecularly defined cellular atlas of the entire mouse brain with isotropic single-cell resolution

Mengting Zhao, Jiandong Zhou, Tao Jiang, Miao Ren, Chuhao Dou, Lingyi Cai, Shengda Bao, Xueyan Jia, Zhaoyang Meng, Feifang Tang, Zhao Feng, Jing Yuan, Xiaoquan Yang, Hui Gong, Qingming Luo (), Xiangning Li () and Anan Li ()
Additional contact information
Mengting Zhao: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering
Jiandong Zhou: Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics
Tao Jiang: JITRI, HUST-Suzhou Institute for Brainsmatics
Miao Ren: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering
Chuhao Dou: Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics
Lingyi Cai: Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics
Shengda Bao: Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics
Xueyan Jia: JITRI, HUST-Suzhou Institute for Brainsmatics
Zhaoyang Meng: Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics
Feifang Tang: Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics
Zhao Feng: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering
Jing Yuan: JITRI, HUST-Suzhou Institute for Brainsmatics
Xiaoquan Yang: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering
Hui Gong: JITRI, HUST-Suzhou Institute for Brainsmatics
Qingming Luo: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering
Xiangning Li: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering
Anan Li: Hainan University, State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract The mammalian brain comprises a vast number of neurons, exhibiting remarkable diversity in both molecular composition and spatial distribution. However, a comprehensive understanding of how these neurons are organized within the brain remains elusive, largely due to the lack of systematic studies providing three-dimensional coverage of molecularly defined neurons across the entire brain. In this study, we utilized transgenic mice and fMOST imaging to map the spatial distribution of glutamatergic, GABAergic, and modulatory neurons at the single-cell level throughout the whole brain. Our approach enabled precise registration of individual cells to the standardized brain coordinate framework, facilitating the construction of whole-brain cell atlases for commonly used Cre recombinase driver lines. Analysis revealed diverse cellular composition patterns across the brain, aligning with the boundaries of known brain regions in some areas while uncovering previously uncharacterized subdivisions in others. Notably, cortical and subcortical nuclei as small as approximately one millimeter in size exhibited intricate three-dimensional organization, suggesting the presence of finer functional zones.

Date: 2025
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DOI: 10.1038/s41467-025-65238-5

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