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Related Experiment Video

Updated: Jul 13, 2025

Large-scale Three-dimensional Imaging of Cellular Organization in the Mouse Neocortex
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Interindividual variation in human cortical cell type abundance and expression.

Nelson Johansen1, Saroja Somasundaram1, Kyle J Travaglini1

  • 1Allen Institute for Brain Science, Seattle, WA 98109, USA.

Science (New York, N.Y.)
|October 12, 2023
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Summary

This study maps neocortical cell types in 75 individuals, revealing significant interindividual variation in cell abundances and gene expression, especially in specific neuron and microglia populations. This provides a baseline for understanding cellular variation in health and disease.

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Area of Science:

  • Neuroscience
  • Genomics
  • Cell Biology

Background:

  • Single-cell transcriptomics has identified conserved neocortical cell types.
  • Previous studies were limited by small postmortem sample sizes.

Purpose of the Study:

  • To characterize cell type variation across a large cohort of adult individuals.
  • To establish a baseline for cellular variation in the human neocortex.

Main Methods:

  • Single-nucleus RNA sequencing of neocortical tissue from 75 adult surgical patients.
  • Analysis of cell type abundance and gene expression signatures.
  • Correlation of genomic variation with gene expression.

Main Results:

  • Identification of 125 robust neocortical cell types in the middle temporal gyrus.
  • Significant interindividual variance in cell abundances and gene expression, particularly in deep-layer glutamatergic neurons and microglia.
  • Genomic variation associated with expression of 150-250 genes across most cell types.

Conclusions:

  • Human neocortical cell types exhibit substantial interindividual variation.
  • Age, sex, ancestry, disease, and cell state explain a minority of this variance.
  • This comprehensive characterization serves as a crucial baseline for future studies in neurological health and disease.