Gene expression analyses reveal molecular relationships among 20 regions of the human CNS

Abstract

Transcriptional profiling was performed to survey the global expression patterns of 20 anatomically distinct sites of the human central nervous system (CNS). Forty-five non-CNS tissues were also profiled to allow for comparative analyses. Using principal component analysis and hierarchical clustering, we were able to show that the expression patterns of the 20 CNS sites profiled were significantly different from all non-CNS tissues and were also similar to one another, indicating an underlying common expression signature. By focusing our analyses on the 20 sites of the CNS, we were able to show that these 20 sites could be segregated into discrete groups with underlying similarities in anatomical structure and, in many cases, functional activity. These findings suggest that gene expression data can help define CNS function at the molecular level. We have identified subsets of genes with the following patterns of expression: (1) across the CNS, suggesting homeostatic/housekeeping function; (2) in subsets of functionally related sites of the CNS identified by our unsupervised learning analyses; and (3) in single sites within the CNS, indicating their participation in distinct site-specific functions. By performing network analyses on these gene sets, we identified many pathways that are upregulated in particular sites of the CNS, some of which were previously described in the literature, validating both our dataset and approach. In summary, we have generated a database of gene expression that can be used to gain valuable insight into the molecular characterization of functions carried out by different sites of the human CNS.

Arhgap36-dependent activation of Gli transcription factors

“…Transcriptional profiling data from human medulloblastomas was compiled from previously published series (30)(31)(32)(33) and a new series generated at the German Cancer Research Center (Gene Expression Omnibus accession nos. GSE37418, GSE49243, and GSE10327), for a total of 436 medulloblastoma and 18 normal cerebellum samples.…”

“…We next compiled transcriptional profiles of 436 medulloblastoma and 18 normal cerebellum samples, using a microarray series generated through the PedBrain Tumor Project of the International Cancer Genome Consortium and published microarray datasets (30)(31)(32)(33). The medulloblastoma samples were segregated according to molecular subtypes as described (34,35), which includes tumors associated with WNT pathway activation (group 1), SHH pathway activation (group 2), or more complex etiologies (groups 3 and 4).…”

Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain

“…Blood contains organ-specific gene products that are released into circulation through tissue damage, enzymatic cleavage from the cell membrane, or normal blood secretion, providing a source of clinically useful biomarkers for differentiating normal from diseased organs (15). A comparison with published human tissue expression atlases (data on deep comparative transcriptome analyses of multiple organs) (16)(17)(18) showed that 130 of the 320 neuron-specific genes from Cahoy et al (3), of which our 170 genes are a subset, are n = 3 genes*, Accuracy = 80%*** n = 2 genes*, Accuracy = 80%*** n = 3 genes**, Accuracy = 79%*** n = 2 genes**, Accuracy = 76%*** n = 12 genes*, Accuracy = 89%*** n = 6 genes, Accuracy = 74%*** n = 12 genes, Accuracy = 64%*** Gene Ontology gene sets with consistent differences in relative gene expression (reordering of gene set components) between clusters. P values for added-value of GO term vs. random sets of neuron-specific genes (genes, size n), and separability of clusters (accuracy) vs. randomly distributed pixels, calculated by permuting gene and pixel cluster labels, respectively.…”

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

“…We have analyzed the mRNA microarray data, which were generated from 353 human tissue samples [18] and deposited in the databank (Oncomine 4.4; www.oncomine. org).…”