Spatially resolved gene regulatory and disease-related vulnerability map of the adult Macaque cortex.
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Lei Ying, Cheng Mengnan, Li Zihao, Zhuang Zhenkun, Wu Liang, Sun Yunong, Han Lei, Huang Zhihao, Wang Yuzhou, Wang Zifei, Xu Liqin, Yuan Yue, Liu Shang, Pan Taotao, Xie Jiarui, Liu Chuanyu, Volpe Giacomo, Ward Carl, Lai Yiwei, Xu Jiangshan, Wang Mingyue, Yu Hao, Sun Haixi, Yu Qichao, Wu Liang, Wang Chunqing, Wong Chi Wai, Liu Wei, Xu Liangzhi, Wei Jingkuan, Chen Dandan, Shang Zhouchun, Li Guibo, Ma Kun, Cheng Le, Ling Fei, Tan Tao, Chen Kai, Tasic Bosiljka, Dean Michael, Ji Weizhi, Yang Huanming, Gu Ying, Esteban Miguel A, Li Yuxiang, Chen Ao, Niu Yuyu, Zeng Hongkui, Hou Yong, Liu Longqi, Liu Shiping, Xu Xun
Аннотация
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.