Spatially resolved gene regulatory and disease-related vulnerability map of the adult Macaque cortex

Ying Lei, Mengnan Cheng, Zihao Li, Zhenkun Zhuang, Liang Wu, Yunong Sun, Lei Han, Zhihao Huang, Yuzhou Wang, Zifei Wang, Liqin Xu, Yue Yuan, Shang Liu, Taotao Pan, Jiarui Xie, Chuanyu Liu, Giacomo Volpe, Carl Ward, Yiwei Lai, Jiangshan Xu, Mingyue Wang, Hao Yu, Haixi Sun, Qichao Yu, Liang Wu, Chunqing Wang, Chi Wai Wong, Wei Liu, Liangzhi Xu, Jingkuan Wei, Dandan Chen, Zhouchun Shang, Guibo Li, Kun Ma, Le Cheng, Fei Ling, Tao Tan, Kai Chen, Bosiljka Tasic, Michael Dean, Weizhi Ji, Huanming Yang, Ying Gu, Miguel A. Esteban, Yuxiang Li, Ao Chen, Yuyu Niu (), Hongkui Zeng (), Yong Hou (), Longqi Liu (), Shiping Liu () and Xun Xu ()
Additional contact information
Ying Lei: BGI-Hangzhou
Mengnan Cheng: BGI-Hangzhou
Zihao Li: BGI-Hangzhou
Zhenkun Zhuang: BGI-Hangzhou
Liang Wu: BGI-Shenzhen
Yunong Sun: BGI-Hangzhou
Lei Han: BGI-Hangzhou
Zhihao Huang: BGI-Shenzhen
Yuzhou Wang: BGI-Shenzhen
Zifei Wang: BGI-Shenzhen
Liqin Xu: BGI-Shenzhen
Yue Yuan: BGI-Hangzhou
Shang Liu: BGI-Shenzhen
Taotao Pan: BGI-Shenzhen
Jiarui Xie: BGI-Shenzhen
Chuanyu Liu: BGI-Hangzhou
Giacomo Volpe: IRCCS-Istituto Tumori “Giovanni Paolo II”. Viale O Flacco 65
Carl Ward: Guangzhou Institutes of Biomedicine and Health, CAS
Yiwei Lai: BGI-Hangzhou
Jiangshan Xu: BGI-Hangzhou
Mingyue Wang: BGI-Hangzhou
Hao Yu: BGI-Shenzhen
Haixi Sun: BGI-Shenzhen
Qichao Yu: BGI-Shenzhen
Liang Wu: BGI-Shenzhen
Chunqing Wang: BGI-Shenzhen
Chi Wai Wong: Huazhen Biosciences
Wei Liu: Huazhen Biosciences
Liangzhi Xu: Huazhen Biosciences
Jingkuan Wei: Kunming University of Science and Technology
Dandan Chen: BGI-GenoImmune, BGI-Shenzhen
Zhouchun Shang: BGI-Shenzhen
Guibo Li: BGI-Shenzhen
Kun Ma: BGI-Shenzhen
Le Cheng: BGI-Yunnan, BGI-Shenzhen
Fei Ling: South China University of Technology
Tao Tan: Kunming University of Science and Technology
Kai Chen: Kunming University of Science and Technology
Bosiljka Tasic: Allen Institute for Brain Science
Michael Dean: Cancer and Inflammation Program, National Cancer Institute at Frederick, Building 560
Weizhi Ji: Kunming University of Science and Technology
Huanming Yang: BGI-Shenzhen
Ying Gu: BGI-Hangzhou
Miguel A. Esteban: BGI-Hangzhou
Yuxiang Li: BGI-Shenzhen
Ao Chen: BGI-Shenzhen
Yuyu Niu: Kunming University of Science and Technology
Hongkui Zeng: Allen Institute for Brain Science
Yong Hou: BGI-Shenzhen
Longqi Liu: BGI-Hangzhou
Shiping Liu: BGI-Hangzhou
Xun Xu: BGI-Hangzhou

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract Single cell approaches have increased our knowledge about the cell type composition of the non-human primate (NHP), but a detailed characterization of area-specific regulatory features remains outstanding. We generated single-cell transcriptomic and chromatin accessibility (single-cell ATAC) data of 358,237 cells from prefrontal cortex (PFC), primary motor cortex (M1) and primary visual cortex (V1) of adult female cynomolgus monkey brain, and integrated this dataset with Stereo-seq (spatial enhanced resolution omics-sequencing) of the corresponding cortical areas to assign topographic information to molecular states. We identified area-specific chromatin accessible sites and their targeted genes, including the cell type-specific transcriptional regulatory network associated with excitatory neurons heterogeneity. We reveal calcium ion transport and axon guidance genes related to specialized functions of PFC and M1, identified the similarities and differences between adult macaque and human oligodendrocyte trajectories, and mapped the genetic variants and gene perturbations of human diseases to NHP cortical cells. This resource establishes a transcriptomic and chromatin accessibility combinatory regulatory landscape at a single-cell and spatially resolved resolution in NHP cortex.

Date: 2022
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DOI: 10.1038/s41467-022-34413-3

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