We demonstrated recently that both constitutive and FAS-triggered apoptosis of human neutrophils are profoundly impaired by Francisella tularensis, but how this is achieved is largely unknown. To test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, we used human oligonucleotide microarrays to identify differentially regulated genes in cells infected with F. tularensis strain LVS compared with uninfected controls.
Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis.
Specimen part, Time
View SamplesDevelopment of a novel CRISPR-derived cell line which is a derivative of CWR22Rv1 cells, called CWR22Rv1-AR-EK, that has lost expression of FL-AR, but retains all endogenous AR-Vs. AR-Vs act unhindered by loss of FL-AR to drive cell growth and expression of androgenic genes. Global transcriptomics demonstrate that AR-Vs drive expression of a cohort of DNA damage response genes and depletion of AR-Vs sensitizes cells to ionizing radiation. Overall design: Transcriptomic profile (mRNA) of AR splice variants in CWR22Rv1 AR-EK cells was generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities.
Specimen part, Cell line, Subject
View SamplesDespite the availability of large-scale transcriptomics data, specific long noncoding RNAs (lncRNAs) expressed in specific brain regions and populations of neurons are poorly understood. Here we report analysis of expression of lncRNAs and mRNAs expressed in hippocampus and prefrontal cortex (PFC), two regions of brain that are involved in memory storage and neuropsychiatric disorders. Our unbiased analyses have identified specific lncRNAs and mRNAs that are enriched in hippocampus and PFC. We have identified several regions in the chromosomes characterized by clustered lncRNA expression suggesting the transcriptional hotspots of lncRNA in the genome. We find that, a subset of lncRNAs and protein coding genes in their vicinity are uniquely co-expressed in specific brain regions and thus presumably co-regulated. Furthermore, specific brain regions and neuronal populations have characteristic lncRNA expression profile. These studies reveal unexpected complexity in the expression profiles of lncRNAs in the mammalian brain. Overall design: Examination of mRNAs and long noncoding RNAs in mouse hippocampus and prefrontal cortex of 8 adult mice.
Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations.
No sample metadata fields
View SamplesInfection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Specimen part, Treatment
View SamplesGene expression microarrays have made a profound impact in biomedical research. The diversity of platforms and analytical methods has made comparison of data from multiple platforms very challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and in house platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by QRT-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent pre-processing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.
A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies.
No sample metadata fields
View SamplesGene expression microarrays have made a profound impact in biomedical research. The diversity of platforms and analytical methods has made comparison of data from multiple platforms very challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and in-house platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by QRT-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent pre-processing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.
A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies.
No sample metadata fields
View SamplesProduction of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, F508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-F508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.
Specimen part, Cell line
View SamplesWe access the activity-dependent genes in olfactory neuron cells with unilateral naris occlusion model with mouse. Overall design: mRNA profile of olfactory epithelia between closed and open sides of mice naris was compared
Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.
Specimen part, Cell line, Subject
View SamplesEffect of SDHB silencing using siRNA methodologies in the tumor phenotype
Cells silenced for SDHB expression display characteristic features of the tumor phenotype.
No sample metadata fields
View SamplesWhen making treatment decisions, oncologists often stratify breast cancers into a low-risk group (ER+, low grade); an intermediate-risk group (ER+, high grade); and a high-risk group that includes Her2+ and triple-negative (ER-/PR-/Her2-) tumors. None of the currently available gene signatures correlates to this clinical classification. We aimed to develop a test that is practical for the oncologists, that offers both molecular characterization of BCs, and improved prediction of prognosis and treatment response. We investigated the molecular basis of such clinical practice by grouping Her2+ and triple-negative breast cancers together during clustering analyses on the genome-wide gene expression profiles of our training cohort, mostly derived from fine needle aspiration biopsies (FNABs) of 149 consecutive evaluable Breast cancers. The analyses consistently divided these tumors into a three-cluster pattern, similar to clinical risk-stratification groups, that was reproducible in published microarray databases (n=2487) annotated with clinical outcomes. The clinicopathologic parameters of each of these three molecular groups were also similar to clinical classification. The low-risk group had good outcomes and benefited from endocrine therapy. Both intermediate- and high-risk groups had poor outcomes and were resistant to endocrine therapy. The latter demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in MYC, E2F1, Ras, -Catenin and IFN- pathways; and poor prognosis predicted by 14 independent prognostic signatures. Based on a multivariate analysis, this new gene signature, termed ClinicoMolecular Triad Classification, predicted recurrence and treatment response better than all pathologic parameters and other prognostic signatures.
A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis.
Specimen part
View Samples