Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography—the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
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We wish to thank the Allen Institute founders, P. G. Allen and J. Allen, for their vision, encouragement, and support. We express our gratitude to past and present Allen Institute staff members R. Adams, K. Aiona, A. Alpisa, J. Arnold, C. Bennet, K. Brouner, S. Butler, E. Byrnes, S. Caldejon, J. Campiche, A. Carey, J. Chen, C. Copeland, C. Cuhaciyan, T. Desta, N. Dotson, S. Faber, T. Fliss, E. Fulfs, G. Gee, T. Gilbert, L. Gourley, G. Gu, J. Heilman, N. Ivanov, K. Keyser, A. Kriedberg, J. Laoenkue, F. Lee, S. Levine, L. Luong, N. Mastan, N. Mosqueda, E. Mott, N. Motz, D. Muzia, K. Ngo, A. Oldre, E. Olson, J. Parente, J. Phillips, L. Potekhina, T. Roberts, K. Roll, D. Rosen, M. Sarreal, S. Shapouri, N. Shapovalova, C. Simpson, D. Simpson, M. Smith, N. Stewart, K. Sweeney, A. Szafer, L. Velasquez, U. Wagley, W. Wakeman, C. White and B. Youngstrom for their technical assistance. We thank C. Long for mechanical engineering contract work. We thank R. Gullapalli, A. McMillan and R. Morales for post-mortem magnetic resonance imaging and radiology interpretation of MR data; J. Cottrell, M. Davis, R. Johnson, K. Moraniec, R. Vigorito, A. Weldon and the NICHD Brain and Tissue Bank for Developmental Disorders for tissue acquisition and processing; J. Davis for donor coordination; F. Mamdani, M. Martin, E. Moon, L. Morgan, B. Rollins and D. Walsh for tissue processing and psychological autopsy (DW); D. Patel for magnetic resonance imaging; and J. Sonnen for consultation on tissue microneuropathology. We also thank the External RNA Controls Consortium (ERCC), the US National Institute of Standards (NIST) and Technology, and M. Salit for access to ERCC transcripts during Phase V testing. We are grateful to Beckman Coulter Genomics (formerly Cogenics) and their staff P. Hurban, E. Lobenhofer, K. Phillips, A. Rouse and S. Beaver for microarray data generation and design of the custom Agilent array. We also wish to thank the Allen Human Brain Atlas Advisory Council members D. Geschwind, R. Gibbs, P. Hof, E. Jones, C. Koch, C. Saper, L. Swanson, A. Toga and D. Van Essen for their scientific guidance and dedication to the successful execution of this project. The project described was supported in part by Grant Numbers 1C76HF15069-01-00 and 1 1C76HF19619-01-00 from the Department of Health and Human Services Health Resources and Services Administration Awards and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Department of Health and Human Services Health Resources and Services Administration Awards. S.G.N.G and L.V.L. were supported by the MRCD, Wellcome Trust and European Union Seventh Framework Programme under grants 241498 EUROSPIN, 242167 SynSys, and 241995 GENCODYS Projects.
The authors declare no competing financial interests.
This file contains Supplementary Methods 1-3 (see pages 1-2 for details), which describe in detail the methodology of tissue preparation, data generation and data analysis techniques utilized for both the project and the manuscript. (PDF 2375 kb)
This file contains Supplementary Figures 1-14 and legends for Supplementary Tables 1-10. (PDF 3460 kb)
This file contains Supplementary Tables 1-10 (see Supplementary Information file for legends). (ZIP 19331 kb)
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Hawrylycz, M., Lein, E., Guillozet-Bongaarts, A. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012). https://doi.org/10.1038/nature11405
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