Charting the Spatial Transcriptome of the Human Cerebral Cortex at Single-Cell Resolution

Abstract

In our pursuit of creating a comprehensive human cortical atlas to understand human intelligence, we examined the single-nuclei transcriptomes of 307,738 cells alongside spatial transcriptomics data from 46,948 VISIUM spots and 1,355,582 Stereo cells. Atlases reveal distinct expression patterns and spatial arrangements of cortical neural cell types. Glutamatergic neurons exhibit precise laminar patterns, often mirroring expression patterns in adjacent cortical regions. Overlaying our atlas with functional networks delineated substantial correlations between neural cell types and cortical region function. Notably, regions involved in processing sensory information (pain) display a pronounced accumulation of extratelencephalic neurons. Additionally, our atlas enabled precise localization of the thicker layer 4 of the visual cortex and an in-depth study of the stabilize the subplate structure, known as layer 6b, revealed specific marker genes and cellular compositions. Collectively, our research sheds light on the cellular foundations of the intricate and intelligent regions within the human cortex.