Charting the spatial transcriptome of the human cerebral cortex at single-cell resolution
A high-resolution spatial physiological atlas of cortical neurons serves as an essential reference for studying neurological diseases and is crucial for a comprehensive understanding of the cortical functions and physiological mechanisms. Although previous studies have elucidated the cellular basis of individual cortex, the molecular characteristics and precise spatial organization of neural cells within multiple human cortex remain incompletely understood. Subcellular-level spatial transcriptomic sequencing and snRNA-seq enabled mapping of 14 human cortical regions, creating a single-cell atlas with transcriptomic data from 1,121,772 nuclei and spatial profiles from 1,888,306 cells to characterize neural cell organization. The atlas reveals distinct expression patterns and spatial arrangements of neural cell types. Glutamatergic neurons show precise laminar patterns, with similar expression in adjacent cortex. SST neurons fall into two transcriptional categories, corresponding to superficial and deep layer distributions. The atlas, integrated with functional networks, highlights correlations between neural cell types and cortical functions, uncovering cell-cell interactions and ligand-receptor patterns with regional differences in neuron-glia communication. It also deciphers transcriptomic differences and cellular composition in layer 4 and the stable subplate (layer 6b) across regions. Our findings offer insights into the cellular foundations of complex and intelligent regions within the human cortex.
Authors
- Peng Huang (ORCID: https://orcid.org/0000-0002-0187-0847)
- Yideng Cai (ORCID: https://orcid.org/0000-0003-3820-1804)
- Zhaochun Xu (ORCID: https://orcid.org/0000-0003-1799-5529)
- Hongxin Liu (ORCID: https://orcid.org/0000-0001-7590-6956)
- Qinghua Jiang (ORCID: https://orcid.org/0000-0002-1827-0389)
- Guangfu Xue (ORCID: https://orcid.org/0000-0002-5718-2314)
- Xiyun Jin (ORCID: https://orcid.org/0000-0003-2795-6451)
- Chenyang Li (ORCID: https://orcid.org/0000-0002-4406-9224)
- Haoxiu Sun (ORCID: https://orcid.org/0000-0001-9339-5790)
- Songren Wei (ORCID: https://orcid.org/0000-0002-2722-451X)
- Rui Cheng (ORCID: https://orcid.org/0000-0002-9398-3514)
- Xiaoyu Lin (ORCID: https://orcid.org/0000-0001-7486-9452)
- Jiangping Xu (ORCID: https://orcid.org/0000-0002-0447-9229)
- Meng Luo (ORCID: https://orcid.org/0000-0003-0622-9060)
- Pingping Wang (ORCID: https://orcid.org/0000-0001-8888-8005)
- Wenyi Yang (ORCID: https://orcid.org/0009-0000-1698-8293)
- Zhigang Liu (ORCID: https://orcid.org/0000-0002-8372-3700)
- Chang Xu (ORCID: https://orcid.org/0000-0002-5659-6654)
- Rui Chen (ORCID: https://orcid.org/0000-0001-9379-2753)
Institutions
- Harbin Medical University (CN)
- Guangdong Medical College (CN)
- Guangdong Pharmaceutical University (CN)
- Harbin Institute of Technology (CN)
- National Medical Products Administration (CN)
- Foshan Maternity and Child Health Care Hospital (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-19
- DOI
- https://doi.org/10.1038/s41467-025-62793-9
- Citations
- 2
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China