Filters
Technology
Platform
GSE6708
Macaca mulatta
10 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Nuclei of the mammalian thalamus are aggregations of neurons with unique architectures and input-output connections, yet the molecular determinants of their organizational specificity remain unknown. By comparing expression profiles of thalamus and cerebral cortex in adult rhesus monkeys we identified transcripts that are unique to dorsal thalamus or to individual nuclei within it. Real-time quantitative polymerase chain reaction and in situ hybridization analyses confirmed the findings. Expression profiling of individual nuclei microdissected from the dorsal thalamus revealed additional subsets of nucleus-specific genes. Functional annotation using Gene Ontology (GO) vocabulary and Ingenuity Pathway analysis revealed over-representation of GO categories related to development, morphogenesis, cell-cell interactions, and extracellular matrix within the thalamus- and nucleus-specific genes-many involved in the Wnt signaling pathway. Examples included the transcription factor TCF7L2, localized exclusively to excitatory neurons, a calmodulin-binding protein PCP4, the bone extracellular matrix molecules SPP1 and SPARC, and other genes involved in axon outgrowth and cell matrix interactions. Other nucleus-specific genes such as CBLN1 are involved in synaptogenesis. The genes identified likely underlie nuclear specification, cell phenotype and connectivity during development and their maintenance in the adult thalamus.
Publication Title
Nucleus- and cell-specific gene expression in monkey thalamus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 87 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.
Publication Title
Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1210 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression patterns in the brain are strongly influenced by the severity of physiological stress at death. This agonal effect, if not well controlled, can lead to spurious findings in case-control comparisons. While many recent studies match samples by tissue pH and clinically recorded agonal conditions, we found that these commonly used indicators were sometimes at odds with observed stress-related patterns of gene expression, and that matching by these criteria still sometimes results in identifying differences between cases and controls that are primarily driven by residual agonal effects. This problem is analogous to the one in genetic studies, where race and ethnicity are often imprecise proxies for complex environmental and genetic factors.
Publication Title
Sample matching by inferred agonal stress in gene expression analyses of the brain.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 667 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A cardinal symptom of Major Depressive Disorder (MDD) is the disruption of circadian patterns. Yet, to date, there is no direct evidence of circadian clock dysregulation in the brains of MDD patients. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain was difficult to characterize. Here we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-hour cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses ('Controls') and 34 MDD patients. Our dataset covered ~12,000 transcripts in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (AnCg), hippocampus (HC), amygdala (AMY), nucleus accumbens (NAcc) and cerebellum (CB). Several hundred transcripts in each region showed 24-hour cyclic patterns in Controls, and >100 transcripts exhibited consistent rhythmicity and phase-synchrony across regions. Among the top ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERB), DBP, BHLHE40(DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in MDD brains, due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This is the first transcriptome-wide analysis of cyclic patterns in the human brain and demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggest novel molecular targets for treatment of mood disorders.
Publication Title
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pluripotent stem cells, including human embryonic stem (hES) and induced pluripotent stem (hiPS) cells, have been regarded as useful sources for cell?based transplantation therapy. However immunogenicity of the cells remains the major determinant for successful clinical application. We report the examination of several hES cell lines (NTU1 and H9), hiPS cell lines, and their derivatives (including stem cell?derived hepatocytes) for the expression of major histocompatibility complex (MHC), natural killer (NK) cell receptor (NKp30, NKp44, NKp46) ligand, immune?related genes, human leukocyte antigen (HLA) haplotyping, and the effects in functional mixed lymphocyte reaction (MLR). Flow cytometry showed lower levels (percentages and fluorescence intensities) of MHC class I (MHC?I) molecules, 2?microglobulin and HLA?E in undifferentiated stem cells, but the levels were increased after co?treatment with interferon gamma and/or in vitro differentiation. Antigen presenting cell markers (CD11c, CD80 and CD86) and MHC?II (HLA?DP, DQ and DR) remained low throughout the treatments. Recognitions of stem cells/derivatives by NK lysis receptors were lower or absent. Activation of responder lymphocytes was significantly lower by undifferentiated stem cells than by allogeneic lymphocytes in MLR, but differentiated NTU1 hES cells induced a cell number?dependent lymphocyte proliferation comparable with that by allogeneic lymphocytes. Interestingly activation of lymphocytes by differentiated hiPS cells or H9 cells became blunted at higher cell numbers. Real?time RT?PCR showed significant differential expression of immune privilege genes (TGF?2, Arginase 2, Indole 1, GATA3, POMC, VIP, CALCA, CALCB, IL?1RN, CD95L, CR1L, Serpine 1, HMOX1, IL6, LGALS3, HEBP1, THBS1, CD59 and LGALS1) in pluripotent stem cells/derivatives when compared to somatic cells. It is concluded that pluripotent stem cells/derivatives are predicted to be immunogenic, though evidences suggest some levels of potential immune privilege. In addition, differential immunogenicity may exist between different pluripotent stem cell lines and their derivatives
Publication Title
Characteristic expression of major histocompatibility complex and immune privilege genes in human pluripotent stem cells and their derivatives.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TBR1 is a forebrain specific T-box transcription factor. Tbr1-/- mice have been characterized by defective axonal projections from cerebral cortex and abnormal neuronal migration of cerebral cortex and amygdala.
Publication Title
Tbr1 haploinsufficiency impairs amygdalar axonal projections and results in cognitive abnormality.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
We have sequenced the polysome-associated translating mRNAs from stage-matched wild-type and eif3ha morphant embryos at ~24 hpf stage to identify transcripts translationally regulated by eIF3ha. As a control, we have also sequenced total mRNAs from the stage-matched wild-type and eif3ha morphants as well at ~ 24 hpf. Overall design: Polysome-associated mRNAs were isolated from 300 zebrafish embryos. Total RNA was isolated from 50 zebrafish embryos. Single 36-base pair reads were sequenced on the Illumina Genome Analyzer Iix.
Publication Title
Translation initiation factor eIF3h targets specific transcripts to polysomes during embryogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip (gene symbol), Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
Publication Title
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
Publication Title
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples