Transcriptomic cytoarchitecture reveals principles of human neocortex organization

Science 2023 186 cites
2023:192024:442025:602026:63
2023 2026
186

Jorstad, Nikolas L. and Close, Jennie and Johansen, Nelson and Yanny, Anna Marie and Barkan, Eliza R. and Travaglini, Kyle J. and Bertagnolli, Darren and Campos, Jazmin and Casper, Tamara and Crichton, Kirsten and Dee, Nick and Ding, Song-Lin and Gelfand, Emily and Goldy, Jeff and Hirschstein, Daniel and Kiick, Katelyn and Kroll, Matthew and Kunst, Michael and Lathia, Kanan and Long, Brian and Martin, Naomi and McMillen, Delissa and Pham, Trangthanh and Rimorin, Christine and Ruiz, Augustin and Shapovalova, Nadiya and Shehata, Soraya and Siletti, Kimberly and Somasundaram, Saroja and Sulc, Josef and Tieu, Michael and Torkelson, Amy and Tung, Herman and Callaway, Edward M. and Hof, Patrick R. and Keene, C. Dirk and Levi, Boaz P. and Linnarsson, Sten and Mitra, Partha P. and Smith, Kimberly and Hodge, Rebecca D. and Bakken, Trygve E. and Lein, Ed S

Abstract

Variation in cytoarchitecture is the basis for the histological definition of cortical areas. We used single cell transcriptomics and performed cellular characterization of the human cortex to better understand cortical areal specialization. Single-nucleus RNA-sequencing of 8 areas spanning cortical structural variation showed a highly consistent cellular makeup for 24 cell subclasses. However, proportions of excitatory neuron subclasses varied substantially, likely reflecting differences in connectivity across primary sensorimotor and association cortices. Laminar organization of astrocytes and oligodendrocytes also differed across areas. Primary visual cortex showed characteristic organization with major changes in the excitatory to inhibitory neuron ratio, expansion of layer 4 excitatory neurons, and specialized inhibitory neurons. These results lay the groundwork for a refined cellular and molecular characterization of human cortical cytoarchitecture and areal specialization.

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