High throughput analysis of gene expression in the human brain

Colantuoni, Carlo; Purcell, Amy E.; Bouton, Christopher M. L. S.; Pevsner, Jonathan

doi:10.1002/(sici)1097-4547(20000101)59:1<1::aid-jnr1>3.0.co;2-2

Cited by 72 publications

(31 citation statements)

References 95 publications

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“…However, the brain remains a difficult organ to study, in part due to the nuclear, laminar, and cellular heterogeneity of brain regions and cell types (107,108). Thus, a combination of single-cell analysis with cDNA microarrays is a highly desirable paradigm whereby expression profiles of single populations of neuronal and noneuronal subtypes can be analyzed and compared under normal and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

et al. 2004

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Technical and experimental advances in microaspiration techniques, RNA amplification, quantitative real-time polymerase chain reaction (qPCR), and cDNA microarray analysis have led to an increase in the number of studies of single-cell gene expression. In particular, the central nervous system (CNS) is an ideal structure to apply single-cell gene expression paradigms. Unlike an organ that is composed of one principal cell type, the brain contains a constellation of neuronal and noneuronal populations of cells. A goal is to sample gene expression from similar cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and noneuronal cells. The unprecedented resolution afforded by singlecell RNA analysis in combination with cDNA microarrays and qPCR-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease states. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models as well as postmortem human brain tissues. This focused review illustrates the potential power of single-cell gene expression studies within the CNS in relation to neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia, respectively. KEY WORDS:Alzheimer's disease; cDNA microarray; cholinergic basal forebrain; dopamine receptors; expression profiling; protein phosphatases; RNA amplification; schizophrenia; single-cell microaspiration. Abbreviations (note the use of the NCBI-Unigene annotation): 3Rtau, three-repeat tau; 4Rtau, four-repeat tau; ACT, alpha-1-antichymotrypsin; ACTB, beta-actin; AGER, advanced glycosylation end product-specific receptor; APOE, apolipoprotein E; APP, amyloid-beta precursor protein; arc, activity regulated cytoskeletal-associated protein; BAX,

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Section: Discussionmentioning

confidence: 99%

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

et al. 2004

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“…However, the brain remains a difficult organ to study, in part due to the nuclear, laminar, and cellular heterogeneity of brain regions and cell types. 145,146,209,210 Unlike an organ that is comprised of one principal cell type, the brain contains a constellation of neuronal and nonneuronal populations of cells. Importantly, creating a molecular fingerprint of single neurons that are selectively vulnerable requires their precise localization within a defined brain region.…”

Section: Resultsmentioning

confidence: 99%

Single cell gene expression profiling in Alzheimer’s disease

et al. 2006

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Summary: Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

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“…With respect to microarray analysis, there should be documentation of sufficient sensitivity to detect changes in rare transcripts, recognizing in particular that the gene causing the disorder may only be expressed at a specific age of development, that several genes may be involved, or that changes may be secondary rather than primary. Additionally, an acceptable panel of statistical methods should be used and the results must be confirmed and verified by independent procedures [4,7,32,33] The authors fully recognize all of the aforementioned requirements, but note the extremely limited availability of postmortem samples from patients with TS and suggest that even small-scale brain gene expression studies can provide important pathophysiological clues.…”

Section: Discussionmentioning

confidence: 96%