Comparative transcriptomics reveals human-specific cortical features

• DOI: 10.1126/science.ade9516
• Publication Date: 2023-10-12T18:00:31Z
• Authors: Nikolas L. Jorstad; Janet H. T. Song; David Exposito-Al...; Hamsini Suresh; Nathan Castro-Pac...; Fenna M. Krienen; Anna Marie Yanny; Jennie Close; Emily Gelfand; Brian Long; Stephanie C. Seeman; Kyle J. Travaglini; Soumyadeep Basu; Marc Beaudin; Darren Bertagnolli; Megan Crow; Song-Lin Ding; Jeroen Eggermont; Alexandra Glandon; Jeff Goldy; Katelyn Kiick; Thomas Kroes; Delissa McMillen; Trangthanh Pham; Christine Rimorin; Kimberly Siletti; Saroja Somasundaram; Michael Tieu; Amy Torkelson; Guoping Feng; William D. Hopkins; Thomas Höllt; C. Dirk Keene; Sten Linnarsson; Steven A. McCarroll; Boudewijn P. Leli...; Chet C. Sherwood; Kimberly Smith; Christopher A. Walsh; Alexander Dobin; Jesse Gillis; Ed S. Lein; Rebecca D. Hodge; Trygve E. Bakken
• Keywords: Gorilla gorilla; Cognition; Pan troglodytes; Species Specificity; Gene Expression Profiling; Animals; Humans; Hominidae; Neocortex; Transcriptome; Macaca mulatta; Phylogeny; Temporal Lobe

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG. Microglia, astrocytes, and oligodendrocytes had more-divergent expression across species compared with neurons or oligodendrocyte precursor cells, and neuronal expression diverged more rapidly on the human lineage. Only a few hundred genes showed human-specific patterning, suggesting that relatively few cellular and molecular changes distinctively define adult human cortical structure.