Comparative transcriptomics reveals human-specific cortical features

Humans have unique cognitive abilities among primates, including language, but their molecular, cellular, and circuit substrates are poorly understood. We used comparative single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets from the middle temporal gyrus (MTG) to understand human-specific features of cellular and molecular organization. Human, chimpanzee, and gorilla MTG showed highly similar cell type composition and laminar organization, and a large shift in proportions of deep layer intratelencephalic-projecting neurons compared to macaque and marmoset. Species differences in gene expression generally mirrored evolutionary distance and were seen in all cell types, although chimpanzees were more similar to gorillas than humans, consistent with faster divergence along the human lineage. Microglia, astrocytes, and oligodendrocytes showed accelerated gene expression changes compared to neurons or oligodendrocyte precursor cells, indicating either relaxed evolutionary constraints or positive selection in these cell types. Only a few hundred genes showed human-specific patterning in all or specific cell types, and were significantly enriched near human accelerated regions (HARs) and conserved deletions (hCONDELS) and in cell adhesion and intercellular signaling pathways. These results suggest that relatively few cellular and molecular changes uniquely define adult human cortical structure, particularly by affecting circuit connectivity and glial cell function.
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@article{ bib:2022_great_apes,
author = {Nikolas L Jorstad and Janet HT Song and David Exposito-Alonso and Hamsini Suresh and Nathan Castro and Fenna M Krienen and Anna Marie Yanny and Jennie Close and Emily Gelfand and Kyle J Travaglini and Soumyadeep Basu and Marc Beaudin and Darren Bertagnolli and Megan Crow and Song-Lin Ding and Jeroen Eggermont and Alexandra Glandon and Jeff Goldy and Thomas Kroes and Brian Long and Delissa McMillen and Trangthanh Pham and Christine Rimorin and Kimberly Siletti and Saroja Somasundaram and Michael Tieu and Amy Torkelson and Katelyn Ward and Guoping Feng and William D Hopkins and Thomas H{\"o}llt and C Dirk Keene and Sten Linnarsson and Steven A McCarroll and Boudewijn Lelieveldt and Chet C Sherwood and Kimberly Smith and Christopher A Walsh and Alexander Dobin and Jesse Gillis and Ed S Lein and Rebecca D Hodge and Trygve E Bakken},
title = { Comparative transcriptomics reveals human-specific cortical features },
year = { 2022 },
doi = { 10.1101/2022.09.19.508480 },
}