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Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures.

ABSTRACT: Although there have been major advances in elucidating the functional biology of the human brain, relatively little is known of its cellular and molecular organization. Here we report a large-scale characterization of the expression of ?1,000 genes important for neural functions by in situ hybridization at a cellular resolution in visual and temporal cortices of adult human brains. These data reveal diverse gene expression patterns and remarkable conservation of each individual gene's expression among individuals (95%), cortical areas (84%), and between human and mouse (79%). A small but substantial number of genes (21%) exhibited species-differential expression. Distinct molecular signatures, comprised of genes both common between species and unique to each, were identified for each major cortical cell type. The data suggest that gene expression profile changes may contribute to differential cortical function across species, and in particular, a shift from corticosubcortical to more predominant corticocortical communications in the human brain.

SUBMITTER: Zeng H

PROVIDER: S-EPMC3328777 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures.

Zeng Hongkui H Shen Elaine H EH Hohmann John G JG Oh Seung Wook SW Bernard Amy A Royall Joshua J JJ Glattfelder Katie J KJ Sunkin Susan M SM Morris John A JA Guillozet-Bongaarts Angela L AL Smith Kimberly A KA Ebbert Amanda J AJ Swanson Beryl B Kuan Leonard L Page Damon T DT Overly Caroline C CC Lein Ed S ES Hawrylycz Michael J MJ Hof Patrick R PR Hyde Thomas M TM Kleinman Joel E JE Jones Allan R AR

Cell 20120401 2

Although there have been major advances in elucidating the functional biology of the human brain, relatively little is known of its cellular and molecular organization. Here we report a large-scale characterization of the expression of ∼1,000 genes important for neural functions by in situ hybridization at a cellular resolution in visual and temporal cortices of adult human brains. These data reveal diverse gene expression patterns and remarkable conservation of each individual gene's expression ...[more]

PMID: 22500809

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Project description:Despite their diminutive size, islets of Langerhans play a large role in maintaining systemic energy balance in the body. New technologies have enabled us to go from studying the whole pancreas to isolated whole islets, to partial islet sections, and now to islet substructures isolated from within the islet. Using a microfluidic nanodroplet-based proteomics platform coupled with laser capture microdissection and field asymmetric waveform ion mobility spectrometry, we present an in-depth investigation of protein profiles specific to features within the islet. These features include the islet-acinar interface vascular tissue, inner islet vasculature, isolated endocrine cells, whole islet with vasculature, and acinar tissue from around the islet. Compared to interface vasculature, unique protein signatures observed in the inner vasculature indicate increased innervation and intra-islet neuron-like crosstalk. We also demonstrate the utility of these data for identifying localized structure-specific drug–target interactions using existing protein/drug binding databases. Graphical Abstract Highlights • We differentiated intra-islet substructures by their proteome profiles in situ.• We demonstrated significant functional differences between vasculature types.• Novel differences in innervation and colocalization of nerves were observed.• We demonstrated a depth of coverage useful for predictive binding discovery assays.• We identified pathways with these techniques that could aid drug characterizations. In Brief Improved sample handling techniques have enabled us to go from studying the whole pancreas, to isolated whole islets, to islet sections, and now to islet substructures isolated from within islet sections. Using a microfluidic nanodroplet-based proteomics platform coupled with laser capture microdissection and field asymmetric waveform ion mobility spectrometry, we present an in-depth investigation of protein profiles from intra-islet features. The protein coverage and expression profiles obtained are sufficient to fully distinguish each of these features while presenting their own unique proteome signatures.

Dataset Information

Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures.

Publications

Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures.

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