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

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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.

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Abbreviations

ADORA2A :

Adenosine A2a receptor

AMPH :

Amphiphysin (Stiff–Man syndrome with breast cancer 128 kDa autoantigen)

CACNA1A :

Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit

CACNA1B :

Calcium channel, voltage-dependent, L type, alpha 1B subunit

CNS:

Central nervous system

CRTAM :

Class I MHC-restricted T cell-associated molecule

CTP:

Cytosine triphosphate

DLG2 :

Discs, large homologue 2, chapsyn-110 (Drosophila)

DLG4 :

Discs, large homologue 4 (Drosophila)

DLGAP1 :

Discs, large (Drosophila) homologue-associated protein 1

DNM1 :

Dynamin 1

DRD2 :

Dopamine receptor D2EDNRB-endothelin receptor type B

EPS15 :

Epidermal growth factor receptor pathway substrate 15

FOSB :

FBJ murine osteosarcoma viral oncogene homologue B

FYN :

FYN oncogene related to SRC, FGR, and YES

GABRA6 :

Gamma-aminobutyric acid (GABA) A receptor, alpha 6

GPCR:

G-protein coupled receptor

GRIK2 :

Glutamate receptor, ionotropic, kainate 2

GRIN1 :

Glutamate receptor, ionotropic, N-methyl D-aspartate 1

GRM3 :

Glutamate receptor, metabotropic 3

IPKB:

Ingenuity Pathways Knowledge Base

IVT:

In vitro transcription

MBP :

Myelin basic protein

PCA:

Principal component analysis

PCR:

Polymerase chain reaction

PMCH :

Pro-melanin-concentrating hormone

PMI:

Postmortem interval

PNS:

Peripheral nervous system

PTPN5 :

Protein tyrosine phosphatase, nonreceptor type 5

qPCR:

Quantitative polymerase chain reaction

RAB3A :

RAB3A, member RAS oncogene family

RMA:

Robust multiarray analysis; robust multichip average

RNA:

Ribonucleic acid

SFRP4 :

Secreted frizzled-related protein 4

SLC1A3 :

Solute carrier family 1 (glial high affinity glutamate transporter), member 3

SNAP25 :

Synaptosomal-associated protein, 25 kDa

SYT1 :

Synaptotagmin I

SYT3 :

Synaptotagmin III

SYT4 :

Synaptotagmin IV

TH :

Tyrosine hydroxylase

TOI:

Target of interest

UTP:

Uridine triphosphate

VAMP2 :

Vesicle-associated membrane protein 2 (synaptobrevin 2)

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Acknowledgement

We thank Dr. Richard A. Maki for helpful discussion and critical reading of the manuscript.

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Correspondence to Richard B. Roth.

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Roth, R.B., Hevezi, P., Lee, J. et al. Gene expression analyses reveal molecular relationships among 20 regions of the human CNS. Neurogenetics 7, 67–80 (2006). https://doi.org/10.1007/s10048-006-0032-6

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  • DOI: https://doi.org/10.1007/s10048-006-0032-6

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