Single-cell spatial transcriptomic atlas of the whole mouse brain

Lei Han; Zhen Liu; Zehua Jing; Yuxuan Liu; Yujie Peng; Huizhong Chang; Junjie Lei; Kexin Wang; Yuanfang Xu; Wei Liu; Zihan Wu; Qian Li; Xiaoxue Shi; Mingyuan Zheng; He Wang; Juan Deng; Yanqing Zhong; Hailin Pan; Junkai Lin; Ruiyi Zhang; Yu Chen; Jinhua Wu; Mingrui Xu; Biyu Ren; Mengnan Cheng; Qian Yu; Xinxiang Song; Yanbing Lu; Yuanchun Tang; Nini Yuan; Suhong Sun; Yingjie An; Wenqun Ding; Xing Sun; Yanrong Wei; Shuzhen Zhang; Yannong Dou; Yun Zhao; Luyao Han; Qianhua Zhu; Junfeng Xu; Shiwen Wang; Dan Wang; Yinqi Bai; Yikai Liang; Yuan Liu; Mengni Chen; Chun Xie; Binshi Bo; Mei Li; Xinyan Zhang; Wang Ting; Zhenhua Chen; Jiao Fang; Shuting Li; Yujia Jiang; Xing Tan; Guolong Zuo; Yue Xie; Huanhuan Li; Quyuan Tao; Yan Li; Jianfeng Liu; Yuyang Liu; Mingkun Hao; Jingjing Wang; Huiying Wen; Jiabing Liu; Yizhen Yan; Hui Zhang; Yifan Sheng; Shui Yu; Xiaoyan Liao; Xuyin Jiang; Guangling Wang; Huanlin Liu; Congcong Wang; Ning Feng; Xin Liu; Kailong Ma; Xiangjie Xu; Tianyue Han; Huateng Cao; Huiwen Zheng; Yadong Chen; Haorong Lu; Zixian Yu; Jinsong Zhang; Bo Wang; Zhifeng Wang; Qing Xie; Shanshan Pan; Chuanyu Liu; Chan Xu; Luman Cui; Yuxiang Li; Shiping Liu; Sha Liao; Ao Chen; Qing-Feng Wu; Jian Wang; Zhiyong Liu; Yidi Sun; Jan Mulder; Huanming Yang; Xiaofei Wang; Chao Li; Jianhua Yao; Xun Xu; Longqi Liu; Zhiming Shen; Wu Wei; Yan-Gang Sun

doi:10.1016/j.neuron.2025.02.015

Single-cell spatial transcriptomic atlas of the whole mouse brain

Neuron. 2025 Mar 20:S0896-6273(25)00133-3. doi: 10.1016/j.neuron.2025.02.015. Online ahead of print.

Authors

Lei Han¹, Zhen Liu², Zehua Jing³, Yuxuan Liu⁴, Yujie Peng¹, Huizhong Chang¹, Junjie Lei³, Kexin Wang⁵, Yuanfang Xu⁵, Wei Liu⁶, Zihan Wu⁷, Qian Li⁸, Xiaoxue Shi⁵, Mingyuan Zheng⁵, He Wang⁵, Juan Deng⁹, Yanqing Zhong⁵, Hailin Pan¹⁰, Junkai Lin⁵, Ruiyi Zhang⁵, Yu Chen⁵, Jinhua Wu⁶, Mingrui Xu¹¹, Biyu Ren⁵, Mengnan Cheng¹, Qian Yu⁵, Xinxiang Song⁵, Yanbing Lu⁵, Yuanchun Tang¹², Nini Yuan⁵, Suhong Sun⁵, Yingjie An⁵, Wenqun Ding⁵, Xing Sun¹³, Yanrong Wei³, Shuzhen Zhang⁵, Yannong Dou⁵, Yun Zhao⁵, Luyao Han⁵, Qianhua Zhu¹⁰, Junfeng Xu⁵, Shiwen Wang⁵, Dan Wang⁵, Yinqi Bai¹, Yikai Liang⁵, Yuan Liu⁵, Mengni Chen⁵, Chun Xie⁵, Binshi Bo⁵, Mei Li¹⁰, Xinyan Zhang⁵, Wang Ting¹¹, Zhenhua Chen¹¹, Jiao Fang⁵, Shuting Li⁵, Yujia Jiang¹, Xing Tan⁵, Guolong Zuo⁵, Yue Xie¹⁰, Huanhuan Li⁵, Quyuan Tao³, Yan Li⁵, Jianfeng Liu⁵, Yuyang Liu³, Mingkun Hao¹³, Jingjing Wang¹¹, Huiying Wen¹⁴, Jiabing Liu⁵, Yizhen Yan¹⁰, Hui Zhang⁵, Yifan Sheng¹³, Shui Yu⁵, Xiaoyan Liao¹⁰, Xuyin Jiang⁵, Guangling Wang⁵, Huanlin Liu¹⁰, Congcong Wang¹³, Ning Feng¹⁰, Xin Liu⁵, Kailong Ma¹⁰, Xiangjie Xu⁵, Tianyue Han¹⁰, Huateng Cao⁵, Huiwen Zheng³, Yadong Chen¹⁵, Haorong Lu¹⁶, Zixian Yu⁵, Jinsong Zhang¹⁵, Bo Wang¹⁶, Zhifeng Wang¹⁰, Qing Xie¹⁰, Shanshan Pan¹⁵, Chuanyu Liu¹⁷, Chan Xu¹⁵, Luman Cui¹⁰, Yuxiang Li¹⁸, Shiping Liu¹⁹, Sha Liao²⁰, Ao Chen²¹, Qing-Feng Wu¹¹, Jian Wang²², Zhiyong Liu²³, Yidi Sun⁵, Jan Mulder²⁴, Huanming Yang¹⁰, Xiaofei Wang²⁵, Chao Li²⁶, Jianhua Yao²⁷, Xun Xu²⁸, Longqi Liu²⁹, Zhiming Shen³⁰, Wu Wei³¹, Yan-Gang Sun³²

Affiliations

¹ BGI Research, Hangzhou 310030, China.
² Lingang Laboratory, Shanghai 200031, China; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
³ BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
⁵ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
⁶ Lingang Laboratory, Shanghai 200031, China.
⁷ Tencent AI Lab, Shenzhen 518057, China.
⁸ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI Research, Shenzhen 518083, China.
⁹ Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
¹⁰ BGI Research, Shenzhen 518083, China.
¹¹ State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
¹² BGI Research, Hangzhou 310030, China; BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450000, China.
¹³ Lingang Laboratory, Shanghai 200031, China; Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
¹⁴ BGI Research, Hangzhou 310030, China; School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
¹⁵ BGI Research, Qingdao 266555, China.
¹⁶ China National GeneBank, BGI Research, Shenzhen 518120, China.
¹⁷ BGI Research, Shenzhen 518083, China; Shenzhen Proof-of-Concept Center of Digital Cytopathology, BGI Research, Shenzhen 518083, China; Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan 030001, China.
¹⁸ BGI Research, Shenzhen 518083, China; BGI Research, Wuhan 430074, China.
¹⁹ BGI Research, Hangzhou 310030, China; BGI Research, Shenzhen 518083, China.
²⁰ BGI Research, Shenzhen 518083, China; BGI Research, Chongqing 401329, China; JFL-BGI STOmics Center, Jinfeng Laboratory, Chongqing 401329, China.
²¹ BGI Research, Shenzhen 518083, China; BGI Research, Chongqing 401329, China; JFL-BGI STOmics Center, Jinfeng Laboratory, Chongqing 401329, China; Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
²² BGI Research, Shenzhen 518083, China; China National GeneBank, BGI Research, Shenzhen 518120, China.
²³ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai 201602, China.
²⁴ Department of Protein Science, Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm 17121, Sweden; Department of Neuroscience, Karolinska Institute, Stockholm 17177, Sweden.
²⁵ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: xfwang@ion.ac.cn.
²⁶ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: lichao0015@ion.ac.cn.
²⁷ Tencent AI Lab, Shenzhen 518057, China. Electronic address: jianhuayao@tencent.com.
²⁸ BGI Research, Shenzhen 518083, China; Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan 030001, China; Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research, Shenzhen 518083, China. Electronic address: xuxun@genomics.cn.
²⁹ BGI Research, Hangzhou 310030, China; BGI Research, Shenzhen 518083, China; Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan 030001, China. Electronic address: liulongqi@genomics.cn.
³⁰ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai 201602, China. Electronic address: zmshen@ion.ac.cn.
³¹ Lingang Laboratory, Shanghai 200031, China; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: wuwei@lglab.ac.cn.
³² Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: yangang.sun@ion.ac.cn.

PMID: 40132589
DOI: 10.1016/j.neuron.2025.02.015

Abstract

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding the function of the brain. Here, using single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters at single-cell resolution, involving over 4 million cells, as well as for 29,655 genes. We have identified cell clusters exhibiting preference for cortical subregions and explored their associations with brain-related diseases. Additionally, we pinpointed 155 genes with distinct regional expression patterns within the brainstem and unveiled 513 long non-coding RNAs showing region-enriched expression in the adult brain. Parcellation of brain regions based on spatial transcriptomic information revealed fine structure for several brain areas. Furthermore, we have uncovered 411 transcription factor regulons showing distinct spatiotemporal dynamics during neurodevelopment. Thus, we have constructed a single-cell-resolution spatial transcriptomic atlas of the mouse brain with genome-wide coverage.

Keywords: Stereo-seq; development; mouse brain; non-coding gene; parcellation; transcriptome.