An anatomically comprehensive atlas of the adult human brain transcriptome

Michael J Hawrylycz; Ed S Lein; Angela L Guillozet-Bongaarts; Elaine H Shen; Lydia Ng; Jeremy A Miller; Louie Van De Lagemaat; Kimberly A Smith; Amanda Ebbert; Zackery L Riley; Chris Abajian; Christian F Beckmann; Amy Bernard; Darren Bertagnolli; Andrew F Boe; Preston M Cartagena; M Mallar Chakravarty; Mike Chapin; Jimmy Chong; Rachel A Dalley; Barry David Daly; Chinh Dang; Suvro Datta; Nick Dee; Tim A Dolbeare; Vance Faber; David Feng; David R Fowler; Jeff Goldy; Benjamin W Gregor; Zeb Haradon; David R Haynor; John G Hohmann; Steve Horvath; Robert E Howard; Andreas Jeromin; Jayson M Jochim; Marty Kinnunen; Christopher Lau; Evan T Lazarz; Changkyu Lee; Tracy A Lemon; Ling Li; Yang Li; John A Morris; Caroline C Overly; Patrick D Parker; Sheana E Parry; Melissa Reding; Joshua J Royall; Jay Schulkin; Pedro Adolfo Sequeira; Clifford R Slaughterbeck; Simon C Smith; Andy J Sodt; Susan M Sunkin; Beryl E Swanson; Marquis P Vawter; Derric Williams; Paul Wohnoutka; H Ronald Zielke; Daniel H Geschwind; Patrick R Hof; Stephen M Smith; Christof Koch; Seth G N Grant; Allan R Jones

doi:10.1038/nature11405

An anatomically comprehensive atlas of the adult human brain transcriptome

Michael J Hawrylycz, Ed S Lein, Angela L Guillozet-Bongaarts, Elaine H Shen, Lydia Ng, Jeremy A Miller, Louie Van De Lagemaat, Kimberly A Smith, Amanda Ebbert, Zackery L Riley, Chris Abajian, Christian F Beckmann, Amy Bernard, Darren Bertagnolli, Andrew F Boe, Preston M Cartagena, M Mallar Chakravarty, Mike Chapin, Jimmy Chong, Rachel A DalleyBarry David Daly, Chinh Dang, Suvro Datta, Nick Dee, Tim A Dolbeare, Vance Faber, David Feng, David R Fowler, Jeff Goldy, Benjamin W Gregor, Zeb Haradon, David R Haynor, John G Hohmann, Steve Horvath, Robert E Howard, Andreas Jeromin, Jayson M Jochim, Marty Kinnunen, Christopher Lau, Evan T Lazarz, Changkyu Lee, Tracy A Lemon, Ling Li, Yang Li, John A Morris, Caroline C Overly, Patrick D Parker, Sheana E Parry, Melissa Reding, Joshua J Royall, Jay Schulkin, Pedro Adolfo Sequeira, Clifford R Slaughterbeck, Simon C Smith, Andy J Sodt, Susan M Sunkin, Beryl E Swanson, Marquis P Vawter, Derric Williams, Paul Wohnoutka, H Ronald Zielke, Daniel H Geschwind, Patrick R Hof, Stephen M Smith, Christof Koch, Seth G N Grant, Allan R Jones

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	391-399
Number of pages	9
Journal	Nature
Volume	489
Issue number	7416
Early online date	19 Sep 2012
DOIs	https://doi.org/10.1038/nature11405
Publication status	Published - 2012

Keywords

Neuroscience
Genetics
Genomics
Databases

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10.1038/nature11405

http://www.nature.com/nature/journal/v489/n7416/full/nature11405.html#affil-auth

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Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., Van De Lagemaat, L., Smith, K. A., Ebbert, A., Riley, Z. L., Abajian, C., Beckmann, C. F., Bernard, A., Bertagnolli, D., Boe, A. F., Cartagena, P. M., Chakravarty, M. M., Chapin, M., Chong, J., ... Jones, A. R. (2012). An anatomically comprehensive atlas of the adult human brain transcriptome. Nature, 489(7416), 391-399. https://doi.org/10.1038/nature11405

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title = "An anatomically comprehensive atlas of the adult human brain transcriptome",

abstract = "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.",

keywords = "Neuroscience , Genetics , Genomics , Databases",

author = "Hawrylycz, {Michael J} and Lein, {Ed S} and Guillozet-Bongaarts, {Angela L} and Shen, {Elaine H} and Lydia Ng and Miller, {Jeremy A} and {Van De Lagemaat}, Louie and Smith, {Kimberly A} and Amanda Ebbert and Riley, {Zackery L} and Chris Abajian and Beckmann, {Christian F} and Amy Bernard and Darren Bertagnolli and Boe, {Andrew F} and Cartagena, {Preston M} and Chakravarty, {M Mallar} and Mike Chapin and Jimmy Chong and Dalley, {Rachel A} and Daly, {Barry David} and Chinh Dang and Suvro Datta and Nick Dee and Dolbeare, {Tim A} and Vance Faber and David Feng and Fowler, {David R} and Jeff Goldy and Gregor, {Benjamin W} and Zeb Haradon and Haynor, {David R} and Hohmann, {John G} and Steve Horvath and Howard, {Robert E} and Andreas Jeromin and Jochim, {Jayson M} and Marty Kinnunen and Christopher Lau and Lazarz, {Evan T} and Changkyu Lee and Lemon, {Tracy A} and Ling Li and Yang Li and Morris, {John A} and Overly, {Caroline C} and Parker, {Patrick D} and Parry, {Sheana E} and Melissa Reding and Royall, {Joshua J} and Jay Schulkin and Sequeira, {Pedro Adolfo} and Slaughterbeck, {Clifford R} and Smith, {Simon C} and Sodt, {Andy J} and Sunkin, {Susan M} and Swanson, {Beryl E} and Vawter, {Marquis P} and Derric Williams and Paul Wohnoutka and Zielke, {H Ronald} and Geschwind, {Daniel H} and Hof, {Patrick R} and Smith, {Stephen M} and Christof Koch and Grant, {Seth G N} and Jones, {Allan R}",

year = "2012",

doi = "10.1038/nature11405",

language = "English",

volume = "489",

pages = "391--399",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7416",

}

Hawrylycz, MJ, Lein, ES, Guillozet-Bongaarts, AL, Shen, EH, Ng, L, Miller, JA, Van De Lagemaat, L, Smith, KA, Ebbert, A, Riley, ZL, Abajian, C, Beckmann, CF, Bernard, A, Bertagnolli, D, Boe, AF, Cartagena, PM, Chakravarty, MM, Chapin, M, Chong, J, Dalley, RA, Daly, BD, Dang, C, Datta, S, Dee, N, Dolbeare, TA, Faber, V, Feng, D, Fowler, DR, Goldy, J, Gregor, BW, Haradon, Z, Haynor, DR, Hohmann, JG, Horvath, S, Howard, RE, Jeromin, A, Jochim, JM, Kinnunen, M, Lau, C, Lazarz, ET, Lee, C, Lemon, TA, Li, L, Li, Y, Morris, JA, Overly, CC, Parker, PD, Parry, SE, Reding, M, Royall, JJ, Schulkin, J, Sequeira, PA, Slaughterbeck, CR, Smith, SC, Sodt, AJ, Sunkin, SM, Swanson, BE, Vawter, MP, Williams, D, Wohnoutka, P, Zielke, HR, Geschwind, DH, Hof, PR, Smith, SM, Koch, C, Grant, SGN & Jones, AR 2012, 'An anatomically comprehensive atlas of the adult human brain transcriptome', Nature, vol. 489, no. 7416, pp. 391-399. https://doi.org/10.1038/nature11405

TY - JOUR

T1 - An anatomically comprehensive atlas of the adult human brain transcriptome

AU - Hawrylycz, Michael J

AU - Lein, Ed S

AU - Guillozet-Bongaarts, Angela L

AU - Shen, Elaine H

AU - Ng, Lydia

AU - Miller, Jeremy A

AU - Van De Lagemaat, Louie

AU - Smith, Kimberly A

AU - Ebbert, Amanda

AU - Riley, Zackery L

AU - Abajian, Chris

AU - Beckmann, Christian F

AU - Bernard, Amy

AU - Bertagnolli, Darren

AU - Boe, Andrew F

AU - Cartagena, Preston M

AU - Chakravarty, M Mallar

AU - Chapin, Mike

AU - Chong, Jimmy

AU - Dalley, Rachel A

AU - Daly, Barry David

AU - Dang, Chinh

AU - Datta, Suvro

AU - Dee, Nick

AU - Dolbeare, Tim A

AU - Faber, Vance

AU - Feng, David

AU - Fowler, David R

AU - Goldy, Jeff

AU - Gregor, Benjamin W

AU - Haradon, Zeb

AU - Haynor, David R

AU - Hohmann, John G

AU - Horvath, Steve

AU - Howard, Robert E

AU - Jeromin, Andreas

AU - Jochim, Jayson M

AU - Kinnunen, Marty

AU - Lau, Christopher

AU - Lazarz, Evan T

AU - Lee, Changkyu

AU - Lemon, Tracy A

AU - Li, Ling

AU - Li, Yang

AU - Morris, John A

AU - Overly, Caroline C

AU - Parker, Patrick D

AU - Parry, Sheana E

AU - Reding, Melissa

AU - Royall, Joshua J

AU - Schulkin, Jay

AU - Sequeira, Pedro Adolfo

AU - Slaughterbeck, Clifford R

AU - Smith, Simon C

AU - Sodt, Andy J

AU - Sunkin, Susan M

AU - Swanson, Beryl E

AU - Vawter, Marquis P

AU - Williams, Derric

AU - Wohnoutka, Paul

AU - Zielke, H Ronald

AU - Geschwind, Daniel H

AU - Hof, Patrick R

AU - Smith, Stephen M

AU - Koch, Christof

AU - Grant, Seth G N

AU - Jones, Allan R

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Neuroscience

KW - Genetics

KW - Genomics

KW - Databases

U2 - 10.1038/nature11405

DO - 10.1038/nature11405

M3 - Article

C2 - 22996553

VL - 489

SP - 391

EP - 399

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7416

ER -

An anatomically comprehensive atlas of the adult human brain transcriptome

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Keywords

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