Canonical genetic signatures of the adult human brain.
Michael HawrylyczJeremy A MillerVilas MenonDavid FengTim DolbeareAngela L Guillozet-BongaartsAnil G JeggaBruce J AronowChang-Kyu LeeAmy BernardMatthew F GlasserDonna L DierkerJ Formula See Text Rg MencheAaron SzaferForrest CollmanPascal GrangeKenneth A BermanStefan MihalasZizhen YaoLance StewartAlbert-László BarabásiJay SchulkinJohn PhillipsLydia NgChinh DangDavid R HaynorAllan JonesDavid C Van EssenChristof KochEd LeinPublished in: Nature neuroscience (2015)
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.
Keyphrases
- resting state
- functional connectivity
- gene expression
- genome wide
- dna methylation
- genome wide identification
- bioinformatics analysis
- transcription factor
- copy number
- systematic review
- endothelial cells
- stem cells
- high resolution
- single cell
- blood brain barrier
- cell therapy
- emergency department
- mass spectrometry
- subarachnoid hemorrhage
- cerebral ischemia
- white matter