Transcriptomic cytoarchitecture reveals principles of human neocortex organization

• DOI: 10.1101/2022.11.06.515349
• Publication Date: 2022-11-07T05:30:13Z
• Authors: Nikolas L. Jorstad; Jennie Close; Nelson Johansen; Anna Marie Yanny; Eliza R. Barkan; Kyle J. Travaglini; Darren Bertagnolli; Jazmin Campos; Tamara Casper; Kirsten Crichton; Nick Dee; Song-Lin Ding; Emily Gelfand; Jeff Goldy; Daniel Hirschstein; Matthew Kroll; Michael Kunst; Kanan Lathia; Brian Long; Naomi Martin; Delissa McMillen; Trangthanh Pham; Christine Rimorin; Augustin Ruiz; Nadiya Shapovalova; Soraya Shehata; Kimberly Siletti; Saroja Somasundaram; Josef Sulc; Michael Tieu; Amy Torkelson; Herman Tung; Katelyn Ward; Edward M. Callaway; Patrick R. Hof; C. Dirk Keene; Boaz P. Levi; Sten Linnarsson; Partha P. Mitra; Kimberly Smith; Rebecca D. Hodge; Trygve E. Bakken; Ed S. Lein
• Keywords: Cytoarchitecture; Neocortex; Corticogenesis

Abstract Variation in cortical cytoarchitecture is the basis for histology-based definition of areas, such as Brodmann areas. Single cell transcriptomics enables higher-resolution characterization types human cortex, which we used to revisit idea canonical microcircuit and understand functional areal specialization. Deeply sampled single nucleus RNA-sequencing eight areas spanning structural variation showed highly consistent cellular makeup 24 coarse subclasses. However, proportions excitatory neuron subclasses varied strikingly, reflecting differences intra- extracortical connectivity across primary sensorimotor association cortices. Astrocytes oligodendrocytes also laminar organization Primary visual cortex dramatically different organization, including major ratios inhibitory neurons, expansion layer 4 specialized neurons. Finally, gene expression conserved predicts synaptic function Together these results provide a refined molecular that reflects