Expression profile analysis within the human hippocampus: Comparison of CA1 and CA3 pyramidal neurons

Ginsberg, Stephen D.; Che, Shaoli

doi:10.1002/cne.20535

Cited by 55 publications

(55 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Simultaneous quantitative assessment of multiple transcripts by microaspiration, RNA amplification, and custom-designed cDNA microarray analysis provides a paradigm whereby the genetic signature of anatomically defined cells within a specific brain region can be differentiated from neighboring structures. 118,128,129,194 …”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, single cell and population cell molecular fingerprinting necessitates accurate, nondestructive isolation of cells from optimally prepared tissue sections. 118,128,129 Two popular and effective microdissection methodologies include laser capture microdissection (LCM) and microaspiration. Laser capture microdissection employs a high-energy laser source that separates desired cells from the remainder of a tissue section and facilitates transfer of the identified cells to a microfuge tube for downstream genetic analysis.…”

Section: Acquisition Of Cell Populations For Functional Genomicsmentioning

confidence: 99%

“…Regional and single cell gene expression studies within the brains of animal models and human postmortem AD, mild cognitive impairment (MCI), and normal control brain tissues have been performed via microarray and qPCR analysis coupled with TC RNA amplification. 73,119,120,128,129,132,133,138 …”

Section: Rna Amplification Strategiesmentioning

confidence: 99%

“…85,86,128,129,135 For example, quantitative analysis of hippocampal tissue sections double labeled for AO and TS demonstrates approximately 80% of TS-positive NFTs are AO-positive. 31, 158 We have employed a single cell microarray analysis scheme to identify transcripts that are differentially regulated in CA1 neurons that bear NFTs in AD relative to non-tangle-bearing CA1 neurons in normal-aged control brains.…”

Section: Expression Profile Analysis Of Neurofibrillary Tangles In Admentioning

confidence: 99%

“…Moreover, select populations of neurons degenerate, whereas others remain intact during the progression of AD. 118,126,129,193,194 Cholinergic basal forebrain neurons of the NB display phenotypic alterations in cholinergic markers and contain tau pathology in subjects characterized as MCI. 138,195,196 Single cell expression profiling was performed to assess the expression levels of the six tau isoforms (MAPT1-MAPT6; FIG.…”

Section: Single Cell Analysis Of Cbf Neurons In Admentioning

confidence: 99%

See 4 more Smart Citations

Single cell gene expression profiling in Alzheimer’s disease

et al. 2006

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Acquisition Of Cell Populations For Functional Genomicsmentioning

confidence: 99%

Section: Rna Amplification Strategiesmentioning

confidence: 99%

Section: Expression Profile Analysis Of Neurofibrillary Tangles In Admentioning

confidence: 99%

Section: Single Cell Analysis Of Cbf Neurons In Admentioning

confidence: 99%

See 3 more Smart Citations

Single cell gene expression profiling in Alzheimer’s disease

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

Molecular heterogeneity of developing retinal ganglion and amacrine cells revealed through single cell gene expression profiling

Trimarchi

Stadler

Roska

et al. 2007

J of Comparative Neurology

146

223

View full text Add to dashboard Cite

During development of the central nervous system (CNS), cycling uncommitted progenitor cells give rise to a variety of distinct neuronal and glial cell types. As these different cell types are born they progress from newly specified cells to fully differentiated neurons and glia. In order to define the developmental processes of individual cell types, single cell expression profiling was carried out on developing ganglion and amacrine cells of the murine retina. Individual cells from multiple developmental stages were isolated and profiled on Affymetrix oligonucleotide arrays. Two-color fluorescent in situ hybridization on dissociated retinas was used to verify and extend the microarray results by allowing quantitative measurements of a large number of cells coexpressing two genes. Together, these experiments have yielded an expanded view of the processes underway in developing retinal ganglion and amacrine cells, as well as several hundred new marker genes for these cell types. In addition, this study has allowed for the definition of some of the molecular heterogeneity both between developing ganglion and amacrine cells and among subclasses of each cell type.

show abstract

Expression profiling of precuneus layer III cathepsin D‐immunopositive pyramidal neurons in mild cognitive impairment and Alzheimer's disease: Evidence for neuronal signaling vulnerability

Perez

Lee

et al. 2020

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

The precuneus (PreC; Brodmann area 7), a key hub within the default mode network (DMN) displays amyloid and tau‐containing neurofibrillary tangle (NFT) pathology during the onset of Alzheimer's disease (AD). PreC layer III projection neurons contain lysosomal hydrolase cathepsin D (CatD), a marker of neurons vulnerable to NFT pathology. Here we applied single population laser capture microdissection coupled with custom‐designed microarray profiling to determine the genetic signature of PreC CatD‐positive‐layer III neurons accrued from postmortem tissue obtained from the Rush Religious Orders Study (RROS) cases with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD. Expression profiling revealed significant differential expression of key transcripts in MCI and AD compared to NCI that underlie signaling defects, including dysregulation of genes within the endosomal‐lysosomal and autophagy pathways, cytoskeletal elements, AD‐related genes, ionotropic and metabotropic glutamate receptors, cholinergic enzymes and receptors, markers of monoamine neurotransmission as well as steroid‐related transcripts. Pervasive defects in both MCI and AD were found in select transcripts within these key gene ontology categories, underscoring the vulnerability of these corticocortical projection neurons during the onset and progression of dementia. Select PreC dysregulated genes detected via custom‐designed microarray analysis were validated using qPCR. In summary, expression profiling of PreC CatD ‐positive layer III neurons revealed significant dysregulation of a mosaic of genes in MCI and AD that were not previously appreciated in terms of their indication of systems‐wide signaling defects in a key hub of the DMN.

show abstract

Expression profile analysis within the human hippocampus: Comparison of CA1 and CA3 pyramidal neurons

Cited by 55 publications

References 63 publications

Single cell gene expression profiling in Alzheimer’s disease

Single cell gene expression profiling in Alzheimer’s disease

Molecular heterogeneity of developing retinal ganglion and amacrine cells revealed through single cell gene expression profiling

Expression profiling of precuneus layer III cathepsin D‐immunopositive pyramidal neurons in mild cognitive impairment and Alzheimer's disease: Evidence for neuronal signaling vulnerability

Contact Info

Product

Resources

About