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Conserved coexpression at single cell resolution across primate brains

View ORCID ProfileHamsini Suresh, View ORCID ProfileMegan Crow, View ORCID ProfileNikolas Jorstad, View ORCID ProfileRebecca Hodge, View ORCID ProfileEd Lein, View ORCID ProfileAlexander Dobin, View ORCID ProfileTrygve Bakken, View ORCID ProfileJesse Gillis
doi: https://doi.org/10.1101/2022.09.20.508736
Hamsini Suresh
1Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory; NY, USA
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Megan Crow
2Genentech; 1 DNA Way, South San Francisco, CA, USA
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Nikolas Jorstad
3Allen Institute for Brain Science; Seattle, WA, USA
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Rebecca Hodge
3Allen Institute for Brain Science; Seattle, WA, USA
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Ed Lein
3Allen Institute for Brain Science; Seattle, WA, USA
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Alexander Dobin
1Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory; NY, USA
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Trygve Bakken
3Allen Institute for Brain Science; Seattle, WA, USA
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Jesse Gillis
1Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory; NY, USA
4Department of Physiology, University of Toronto; ON, Canada
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  • For correspondence: jesse.gillis@utoronto.ca
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Abstract

Enhanced cognitive function in humans is hypothesized to result from cortical expansion and increased cellular diversity. However, the mechanisms that drive these phenotypic differences remain poorly understood, in part due to the lack of high-quality cellular resolution data in human and non-human primates. Here, we take advantage of single cell expression data from the middle temporal gyrus of five primates (human, chimp, gorilla, macaque and marmoset) to identify 57 homologous cell types and generate cell-type specific gene coexpression networks for comparative analysis. While ortholog expression patterns are generally well conserved, we find 24% of genes with extensive differences between human and non-human primates (3383/14,131), which are also associated with multiple brain disorders. To validate these observations, we perform a meta-analysis of coexpression networks across 19 animals, and find that a subset of these genes have deeply conserved coexpression across all non-human animals, and strongly divergent coexpression relationships in humans (139/3383, <1% of primate orthologs). Genes with human-specific cellular expression and coexpression networks (like NHEJ1, GTF2H2, C2 and BBS5) typically evolve under relaxed selective constraints and may drive rapid evolutionary change in brain function.

One Sentence Summary Cross-primate middle temporal gyrus single cell expression data reveals patterns of conservation and divergence that can be validated with population coexpression networks.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://gillisweb.cshl.edu/Primate_MTG_coexp/

  • https://github.com/gillislab/Primate-MTG-coexpression

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 22, 2022.
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Conserved coexpression at single cell resolution across primate brains
Hamsini Suresh, Megan Crow, Nikolas Jorstad, Rebecca Hodge, Ed Lein, Alexander Dobin, Trygve Bakken, Jesse Gillis
bioRxiv 2022.09.20.508736; doi: https://doi.org/10.1101/2022.09.20.508736
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Conserved coexpression at single cell resolution across primate brains
Hamsini Suresh, Megan Crow, Nikolas Jorstad, Rebecca Hodge, Ed Lein, Alexander Dobin, Trygve Bakken, Jesse Gillis
bioRxiv 2022.09.20.508736; doi: https://doi.org/10.1101/2022.09.20.508736

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