Canonical genetic signatures of the adult human brain

Michael Hawrylycz, Jeremy A. Miller, Vilas Menon, David Feng, Tim Dolbeare, Angela L. Guillozet-Bongaarts, Anil G. Jegga, Bruce J. Aronow, Chang Kyu Lee, Amy Bernard, Matthew F. Glasser, Donna L. Dierker, Jörg Menche, Aaron Szafer, Forrest Collman, Pascal Grange, Kenneth A. Berman, Stefan Mihalas, Zizhen Yao, Lance StewartAlbert László Barabási, Jay Schulkin, John Phillips, Lydia Ng, Chinh Dang, David R Haynor, Allan Jones, David C. Van Essen, Christof Koch, Ed Lein

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry.

Original languageEnglish
Pages (from-to)1832-1844
Number of pages13
JournalNature neuroscience
Volume18
Issue number12
DOIs
StatePublished - Nov 25 2015

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    Hawrylycz, M., Miller, J. A., Menon, V., Feng, D., Dolbeare, T., Guillozet-Bongaarts, A. L., Jegga, A. G., Aronow, B. J., Lee, C. K., Bernard, A., Glasser, M. F., Dierker, D. L., Menche, J., Szafer, A., Collman, F., Grange, P., Berman, K. A., Mihalas, S., Yao, Z., ... Lein, E. (2015). Canonical genetic signatures of the adult human brain. Nature neuroscience, 18(12), 1832-1844. https://doi.org/10.1038/nn.4171