There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of bystander T cell activation occur during immune responses is hotly debated.
Human CD4+ memory T cells are preferential targets for bystander activation and apoptosis.
No sample metadata fields
View SamplesApproximately 60-70% of patients with pulmonary sarcoidosis have a good outcome, with disease that resolves spontaneously. It is unclear why some patients progress to fibrotic disease, and there is currently no marker that differentiates these patients from those with self-limiting lung disease.
Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis.
Sex, Age, Specimen part
View SamplesDC-SIGN is a C-type lectin expressed by dendritic cells (DCs) that binds HIV-1, sequestering it within multivesicular bodies to facilitate transmission to CD4+ T cells. Here we characterize the molecular basis of signalling through DC-SIGN by large-scale gene expression profiling and phosphoproteome analysis. Solitary DC-SIGN activation leads to a phenotypically disparate transcriptional program from Toll-like receptor (TLR) triggering with downregulation of MHC II, CD86, and interferon response genes and with induction of the TLR negative regulator ATF3. Phosphoproteome analysis reveals DC-SIGN signals through the leukemia-associated Rho guanine nucleotide exchange factor (LARG) to induce Rho activity. This LARG activation also occurs on DC HIV exposure and is required for effective HIV viral synapse formation. Taken together HIV mediated DC-SIGN signalling provides a mechanism by which HIV evades the immune response yet induces viral spread.
Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication.
No sample metadata fields
View SamplesAlcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p 0.0001). At FDR 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence.
Specimen part, Disease
View SamplesNeural progenitor cells (hNPC) derived from the developing human brain can be expanded in culture and subsequently differentiated into neurons and glia. They provide an interesting source of tissue for both modeling brain development and future cellular replacement therapies. It is becoming clear that hNPC are regionally and temporally specified depending on which brain region they were isolated from and its developmental stage. We show here that hNPC derived from the developing cortex (hNPCCTX) and ventral midbrain (hNPCVM) have similar morphological characteristics and express the progenitor cell marker nestin. However, hNPCCTX cultures were highly proliferative and produced large numbers of neurons, while hNPCVM divided slowly and produced less neurons but more astrocytes. Microarray analysis revealed a similar expression pattern for some stemness markers between the two growing cultures, overlaid with a regionally specific profile that identified some important differentially expressed neurogenic transcription factors. By over expressing one of these, the transcription factor ASCL1, we were able to regain neurogenesis from hNPCVM cultures which produced larger neurons with more neurites than hNPCCTX, but no fully mature dopamine neurons. Thus hNPC are regionally specified and can be induced to undergo neurogenesis following genetic manipulation. While this restores neuronal production with a region specific phenotype, it does not restore full neurochemical maturation which may require additional factors.
Regionally specified human neural progenitor cells derived from the mesencephalon and forebrain undergo increased neurogenesis following overexpression of ASCL1.
Specimen part
View SamplesAcute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.
Sex, Specimen part, Race
View SamplesWomen suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. This study used a mouse model to dissociate these factors and found no differences in peripheral afferent neurons or in the spinal cord immune response to neuropathic injury. However, it did identify potential sexual dimorphisms in peripheral adaptive immune responses. Overall design: RNA-seq of naïve FACS-purified DRG neurons and MACS-purified DRG neurons after partial sciatic nerve ligation (day 8): comparison of male versus female samples
Sex differences in peripheral not central immune responses to pain-inducing injury.
Sex, Specimen part, Cell line, Subject
View SamplesRenal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Alteration of human blood cell transcriptome in uremia.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesAcute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
No sample metadata fields
View SamplesWe used microarray analysis to examine which genes are differentially expressed in mice that received a combination of fish oil and indomethacin.
Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR(-/-) mice.
Specimen part, Compound
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