Comparative transcriptomics reveals human-specific cortical features

Nikolas L. Jorstad, Janet H. T. Song, David Exposito-Alonso, Hamsini Suresh, Nathan Castro-Pacheco, 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 Eggemont, 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. Lelieveldt, Chet C. Sherwood, Kimberly Smith, Christopher A. Walsh, Alexander Dobin, Jesse Gillis, Ed S. Lein, Rebecca D. Hodge, and Trygve E. Bakken.
Science 2023


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.