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1.
Nature ; 508(7495): 199-206, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24695229

RESUMO

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.


Assuntos
Encéfalo/metabolismo , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Transcriptoma , Anatomia Artística , Animais , Atlas como Assunto , Encéfalo/embriologia , Sequência Conservada/genética , Feto/citologia , Feto/embriologia , Redes Reguladoras de Genes/genética , Humanos , Camundongos , Neocórtex/embriologia , Neocórtex/metabolismo , Especificidade da Espécie
2.
Nature ; 489(7416): 391-399, 2012 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-22996553

RESUMO

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.


Assuntos
Anatomia Artística , Atlas como Assunto , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Perfilação da Expressão Gênica , Transcriptoma/genética , Adulto , Animais , Encéfalo/citologia , Calbindinas , Bases de Dados Genéticas , Dopamina/metabolismo , Saúde , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Hibridização In Situ , Internet , Macaca mulatta/anatomia & histologia , Macaca mulatta/genética , Masculino , Camundongos , Neocórtex/anatomia & histologia , Neocórtex/citologia , Neocórtex/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Densidade Pós-Sináptica/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteína G de Ligação ao Cálcio S100/genética , Especificidade da Espécie
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