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.