Transcriptomic cytoarchitecture reveals principles of human neocortex organization

• Published in: Science (American Association for the Advancement of Science) Vol. 382; no. 6667; p. eadf6812
• Main Authors: Jorstad, Nikolas L, Close, Jennie, Johansen, Nelson, Yanny, Anna Marie, Barkan, Eliza R, Travaglini, Kyle J, Bertagnolli, Darren, Campos, Jazmin, Casper, Tamara, Crichton, Kirsten, Dee, Nick, Ding, Song-Lin, Gelfand, Emily, Goldy, Jeff, Hirschstein, Daniel, Kiick, Katelyn, Kroll, Matthew, Kunst, Michael, Lathia, Kanan, Long, Brian, Martin, Naomi, McMillen, Delissa, Pham, Trangthanh, Rimorin, Christine, Ruiz, Augustin, Shapovalova, Nadiya, Shehata, Soraya, Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Callaway, Edward M, Hof, Patrick R, Keene, C Dirk, Levi, Boaz P, Linnarsson, Sten, Mitra, Partha P, Smith, Kimberly, Hodge, Rebecca D, Bakken, Trygve E, Lein, Ed S
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 13.10.2023
• Subjects: Astrocytes; Brain architecture; Cellular structure; Cerebral cortex; Cortex (somatosensory); Gene expression; Humans; Information processing; Medicin och hälsovetenskap; Molecular structure; Neocortex; Neocortex - metabolism; Neocortex - ultrastructure; Neural networks; Neurons; Neurons - classification; Neurons - metabolism; Nuclei (cytology); Phylogeny; Similarity; Single-Cell Gene Expression Analysis; Somatostatin; Specialization; Transcriptome; Transcriptomics; Variation; Visual cortex
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/SCIENCE.ADF6812

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.