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Charting the spatial transcriptome of the human cerebral cortex at single-cell resolution.

Songren Wei1,2,3, Meng Luo4, Pingping Wang1

  • 1School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin, 150076, China.

Nature Communications
|August 19, 2025
PubMed
Summary

This study maps human cortical neurons using spatial transcriptomics, revealing cell organization and communication patterns. The atlas provides insights into neurological diseases and brain function.

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Area of Science:

  • Neuroscience
  • Genomics
  • Cell Biology

Background:

  • Understanding human cortical functions requires detailed knowledge of neural cell organization.
  • Previous studies lacked comprehensive molecular and spatial data for multiple human cortical regions.

Purpose of the Study:

  • To create a high-resolution spatial physiological atlas of human cortical neurons.
  • To characterize neural cell organization, molecular features, and spatial arrangements across 14 cortical regions.

Main Methods:

  • Subcellular-level spatial transcriptomic sequencing.
  • Single-nucleus RNA sequencing (snRNA-seq).
  • Integration with functional brain networks.

Main Results:

  • Generated a single-cell atlas with transcriptomic data from over 1.1 million nuclei and spatial profiles from over 1.8 million cells.
  • Identified distinct expression patterns and laminar distributions for glutamatergic and SST neurons.
  • Revealed regional differences in neuron-glia communication and cell-cell interactions.

Conclusions:

  • The atlas provides a comprehensive reference for studying neurological diseases and cortical functions.
  • Detailed spatial organization and molecular characteristics of human cortical cells are now better understood.
  • Findings offer insights into the cellular basis of complex intelligent functions in the human cortex.