Gene expression profiles of human prefrontal cortex brain tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33000 | GEO | 2014/07/31
SECONDARY ACCESSION(S): PRJNA146519
REPOSITORIES: GEO
Similar Datasets
Project description:Dissecting the shared etiology of different diseases could benefit from a systematic search for associated molecules and their interactions. We investigated genome-wide disruptions in the co-regulation of genes in two neurodegenerative diseases, Alzheimer's or Huntington's disease (AD or HD), using expression profiles from postmortem prefrontal cortex samples of 624 demented patients and non-demented control individuals with matched genotype and clinical data. A meta-analysis based screen for changes in coordinate expression patterns revealed differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former being dominant for both AD and HD. Integration of disruptions common to AD and HD with large-scale data on protein-protein and protein-DNA interactions yielded a 242-gene sub-network that was enriched for proteins involved in neuronal differentiation and genetic associations to brain structural changes and dementia in subjects aged over 70 years. Replication of the AD DC network in independent human and mouse cohorts lends confidence to the comprehensive view we offer on dysregulated brain molecular pathways in AD and HD. DLPFC (BA9) brain tissues of AD patients, HD patients and non-demented controls samples were obtained from Harvard Brain tissue resource center (HBTRC). The HBTRC samples were primarily of Caucasian ancestry, as only eight non-Caucasian outliers were identified, and therefore excluded for further analysis. Post-mortem interval (PMI) was 17.8+8.3 hours (mean ± standard deviation), sample pH was 6.4±0.3 and RNA integrity number (RIN) was 6.8±0.8 for the average sample in the overall cohort. Tissues were profiled on a custom-made Agilent 44K array (GPL4372). 624 individual DLPFC samples were profiled against a common DLPFC pool constructed from the same set of samples.
2014-07-31 | E-GEOD-33000 | biostudies-arrayexpress
Project description:Alternative polyadenylation (APA) contributes to post-transcriptional regulation, but its role in Alzheimer’s disease (AD) is largely unknown. Using high-resolution SQUARE multiple 3’ primer-based sequencing, we discovered massive APA differences in temporal gyrus tissues from demented AD patients compared to either healthy controls or non-demented donors with AD neuropathology (NDWP). Advanced statistics, microfluidics RT-PCR and protein measurements validated known and novel APA-modified 3’-intact transcripts. Moreover, APA modifications, more than total transcript counts, distinguished AD patients from both controls and NDWP donors and identified cell type-characteristic, cognition-associated and neuropathology-related changes. AD-enhanced APA variants included known therapeutic targets of brain, vascular and autoimmune disorders, predicting co-involvement of these target genes in AD progression; AD/NDWP increases in 3’-intact proteinopathy-related hnRNP mRNAs were inversely associated with protein decreases, whereas NDWP-potentiated cognition was accompanied by distinct ATP and mitochondrial variants. APA variations thus provide a novel resource of unique value for both basic and translational neuroscience researchers.
2017-04-27 | GSE57152 | GEO
Project description:Alternative polyadenylation (APA) contributes to post-transcriptional regulation, but its role in Alzheimer’s disease (AD) is largely unknown. Using high-resolution SQUARE multiple 3’ primer-based sequencing, we discovered massive APA differences in temporal gyrus tissues from demented AD patients compared to either healthy controls or non-demented donors with AD neuropathology (NDWP). Advanced statistics, microfluidics RT-PCR and protein measurements validated known and novel APA-modified 3’-intact transcripts. Moreover, APA modifications, more than total transcript counts, distinguished AD patients from both controls and NDWP donors and identified cell type-characteristic, cognition-associated and neuropathology-related changes. AD-enhanced APA variants included known therapeutic targets of brain, vascular and autoimmune disorders, predicting co-involvement of these target genes in AD progression; AD/NDWP increases in 3’-intact proteinopathy-related hnRNP mRNAs were inversely associated with protein decreases, whereas NDWP-potentiated cognition was accompanied by distinct ATP and mitochondrial variants. APA variations thus provide a novel resource of unique value for both basic and translational neuroscience researchers.
2017-08-01 | GSE70424 | GEO
Project description:Alzheimer's Disease (AD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators.
2011-07-13 | GSE29676 | GEO
Project description:The establishment of ad/abaxial polarity is a fundamental event in plant development. It is critical for correct polar development of the leaf (the upper portion of the leaf is chloroplast rich and optimized for light capture while the lower portion is optimized for gas exchange) and for creating an environment that allows the formation of new meristems (centers of stem cell growth). Class III homeodomain-leucine zipper (HD-ZIPIII) proteins are conserved plant proteins that act as potent regulators of ad/abaxial polarity. HD-ZIPIII protein activity promotes the development of upper (adaxial) leaf fates and meristem formation; in its absence lower (abaxial) leaf fates develop and meristems fail to form. A network of regulatory factors controls the establishment of ad/abaxial leaf fates. However, this network is incomplete and how these factors control one another is poorly understood. Here we report a new family of plant genes, the LITTLE ZIPPER (ZPR) genes (consisting principally of a stretch of leucine zipper similar to the leucine zipper in HD-ZIPIII proteins) that are transcriptionally up-regulated by HD-ZIPIII activity. Furthermore, we show that the ZPR proteins interact with and repress HD-ZIPIII activity, thus forming a negative feedback loop. Our results suggest that HD-ZIPIII proteins exist in active homodimers and, together with the ZPR proteins, in inactive heterodimers. The newly discovered HD-ZIPIII/ZPR regulatory module would not only serve to dampen the effect of fluctuations in HD-ZIPIII protein levels but more importantly would provide a point of regulation - control over the ratio of inactive heterodimers to active homodimers - that could be influenced by other components of the pathway. For instance, the binding of a small hydrophobic molecule to the conserved (yet little understood) START domain present in the HD-ZIPIII proteins may influence the type of dimer formed. Published in: Wenkel, S., Emery, J., Hou, B.-H., Evans, M.M.S. and M.K. Barton, 2007, A Feedback Regulatory Module Formed by LITTLE ZIPPER and HD-ZIPIII Genes. Plant Cell 2007 Keywords: screen for downstream genes, transcription factor induction
2007-12-05 | GSE7003 | GEO
Project description:The establishment of ad/abaxial polarity is a fundamental event in plant development. It is critical for correct polar development of the leaf (the upper portion of the leaf is chloroplast rich and optimized for light capture while the lower portion is optimized for gas exchange) and for creating an environment that allows the formation of new meristems (centers of stem cell growth). Class III homeodomain-leucine zipper (HD-ZIPIII) proteins are conserved plant proteins that act as potent regulators of ad/abaxial polarity. HD-ZIPIII protein activity promotes the development of upper (adaxial) leaf fates and meristem formation; in its absence lower (abaxial) leaf fates develop and meristems fail to form. A network of regulatory factors controls the establishment of ad/abaxial leaf fates. However, this network is incomplete and how these factors control one another is poorly understood. Here we report a new family of plant genes, the LITTLE ZIPPER (ZPR) genes (consisting principally of a stretch of leucine zipper similar to the leucine zipper in HD-ZIPIII proteins) that are transcriptionally up-regulated by HD-ZIPIII activity. Furthermore, we show that the ZPR proteins interact with and repress HD-ZIPIII activity, thus forming a negative feedback loop. Our results suggest that HD-ZIPIII proteins exist in active homodimers and, together with the ZPR proteins, in inactive heterodimers. The newly discovered HD-ZIPIII/ZPR regulatory module would not only serve to dampen the effect of fluctuations in HD-ZIPIII protein levels but more importantly would provide a point of regulation - control over the ratio of inactive heterodimers to active homodimers - that could be influenced by other components of the pathway. For instance, the binding of a small hydrophobic molecule to the conserved (yet little understood) START domain present in the HD-ZIPIII proteins may influence the type of dimer formed. Published in:; Wenkel, S., Emery, J., Hou, B.-H., Evans, M.M.S. and M.K. Barton, 2007, A Feedback Regulatory Module Formed by LITTLE ZIPPER and HD-ZIPIII Genes. Plant Cell 2007 Experiment Overall Design: One of the five Arabidopsis HD-ZIPIII proteins, REVOLUTA, was placed under glucocorticoid control by fusing the glucocorticoid receptor (GR) domain to its amino terminus. This gene fusion was placed under the control of the highly and constitutively expressed viral CaMV35S promoter. Since the HD-ZIPIII genes are controlled by microRNAs, it was also necessary to introduce mutations that disrupted the microRNA complementary sequence. Transgenic Arabidopsis seedlings carrying this construct (GR-REV) as well as wild-type seedlings were grown in liquid culture for ten days. At this point, one flask each of wt and transgenic seedlings was treated with carrier alone (ethanol) and one flask each of wt and transgenic seedlings was treated with dexamethasone. RNA was harvested from these samples after one hour, labeled and hybridized to Affymetrix microarrays.
2008-06-15 | E-GEOD-7003 | biostudies-arrayexpress
Project description:Alzheimer's Disease (AD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 50 AD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of AD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Parkinson's disease and breast cancer, respectively) confirmed their specificity.
2011-07-12 | E-GEOD-29676 | biostudies-arrayexpress
Project description:Along with the two hallmark pathologies—intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques—transcriptional studies suggest that Alzheimer's disease (AD) results from dysfunction of many cellular pathways including synaptic transmission, cytoskeletal dynamics, and apoptosis. While these studies consistently point to the same pathways involved in AD, there is no consensus on which genes in each pathway are disease-relevant, much less on whether these genes play causative roles or are downstream effects of disease progression. To address these issues, we have performed a large-scale transcriptional analysis in brain of individuals with advanced AD and non-demented controls, focusing specifically on CA1 and the relatively less affected CA3. For comparisons between regions and across disease status, we find consistency in both pathway enrichment as well as specific differentially expressed genes across several studies. Furthermore, genes that show decreased expression with AD progression also tend to show enrichment in CA3 (and vice versa), suggesting that transcription levels in a region may reflect that region's vulnerability to disease. In particular, we find several strong candidate vulnerability (ABCA1, MT1H, PDK4, RHOBTB3) and protection (FAM13A1, LINGO2, UNC13C) genes based on expression patterns. We have also applied weighted gene coexpression network analysis (WGCNA) to explore the pathophysiology of AD from a systems perspective, finding modules for major cell types, which each show distinct disease-relevant expression patterns. In particular, a microglial module shows increased expression in the brain of non-demented controls harboring early NFT pathology, suggesting that microglial activation is an early event in AD progression. Total RNA obtained from 60um sections of frozen human hippocampus was collected using scalpel dissection. Control and AD brains were matched for all non-disease characteristics as closely as possible. CA1 and CA3 dissections for a given individual were taken from the same section. Several region- and disease-related comparisons were performed.
2013-06-07 | E-GEOD-29378 | biostudies-arrayexpress
Project description:Gene expression profiling was performed on frontal and temporal cortex from vascular dementia (VaD), Alzheimer's disease (AD), and non-demented controls (Control) obtained from the University of Michigan Brain Bank. Controls and AD cases had no infarcts in the autopsied hemisphere. Vascular dementia cases had low Braak staging.
2019-04-23 | GSE122063 | GEO
Project description:Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimer’s disease. Here, we investigated microglia transcriptomes at bulk and single cell level in non-demented elderly and AD donors using acute human post-mortem cortical brain samples. We identified 7 human microglial subpopulations with heterogeneity in gene expression. Notably, gene expression profiles and subcluster composition of microglia did not differ between AD donors and non-demented elderly in bulk RNA sequencing nor in single-cell sequencing.
2020-09-10 | GSE146639 | GEO