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GSE63129
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Four conditions of cultured CD8+ T cells were analyzed with Affymetrix HG-U133-Plus-2.0 microarrays.
Publication Title
Detection of self-reactive CD8⁺ T cells with an anergic phenotype in healthy individuals.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
NextSeq 500
Description
KRAS mutation is present in about 30% of human lung adenocarcinomas. While recent advances in targeted therapy have shown great promise, KRAS remains undruggable and concurrent alterations in tumor suppressors render KRAS mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS mutant tumors harboring these co-mutations are immunosuppressive mechanisms such as increased presence of suppressive Tregs in tumors and elevated expression of the inhibitory receptor PD-1 on tumor-infiltrating T cells. BET bromodomain inhibitors demonstrate clinical benefit in hematologic malignancies, and prior reports demonstrate their Treg-disruptive effects in a NSCLC model. Targeting PD-1 inhibitory signals through anti-PD-1 antibody blockade has also shown substantial therapeutic impact in lung cancer although these outcomes are still limited to a minor pool of patients. We therefore hypothesized that the BET bromodomain inhibitor JQ1 would synergize with PD-1 blockade to promote robust anti-tumor response in lung cancer. In the present study, using Kras+/LSL-G12D; Trp53L/L (KP) mouse models of non-small cell lung cancer, we identified cooperative effects between JQ1 and anti-PD-1 antibody that included reduced numbers of tumor-infiltrating Tregs and enhanced activation of tumor-infiltrating T cells, which exhibited a Th1 cytokine profile that favored their demonstrated improved effector function. Furthermore, lung-tumor-bearing mice under this combinatorial treatment regimen showed robust and long-lasting anti-tumor responses compared to either agent alone, culminating in substantial improvement in the survival of treated mice. Thus, combining BET bromodomain inhibition with immune checkpoint blockade offers a promising therapeutic approach for solid malignancies such as lung adenocarcinoma. Overall design: Gene expression analyses of tumor nodules in lung tumor-bearing mice treated with Vehicle (control), JQ1 (Bromodomain inhibitor) and/or anti-PD-1 antibody
Publication Title
BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in <i>Kras</i>-Mutant Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 192 Downloadable Samples
- NextSeq 500
Description
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response. By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that support enhanced T cell activation and improved function of antigen presenting cells. The bromodomain inhibitor JQ1 attenuated CD4+Foxp3+ T regulatory cell suppressive function and synergized with ricolinostat to facilitate immune-mediated tumor growth arrest, leading to prolonged survival of mice with lung adenocarcinomas. Collectively, our findings highlight the immunomodulatory effects of two epigenetic modifiers that, together, promote T cell-mediated anti-tumor immunity and demonstrate their therapeutic potential for treatment of NSCLC. Overall design: Single-cell comparison of vehicle (control) and HDAC inhibitor (ricolinostat)-treated tumor infiltrating T cells and macrophages
Publication Title
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Osteoarthritis (OA) is a common degenerative disease of the joint. Data from our lab indicates that Hedgehog (Hh) signaling is activated in human OA and murine models of OA (Lin et al., 2009, Nature Medicine). To identify Hh target genes, microarray analyses were performed to detect changes in gene expression when the Hh pathway was inhibited in human OA cartilage samples.
Publication Title
Regulation of Cholesterol Homeostasis by Hedgehog Signaling in Osteoarthritic Cartilage.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 67 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-seq libraries purified from the visual cortices of neurons expressing Emx-, GAD2-, PV-, SST-, or VIP-Cre using the Ribotag allele. Seq libraries are provided from mice raised in standard housing, or housed in the dark for two weeks (dark-housed), or dark-housed and then exposed to light for 1, 3, or 7.5 hours. These seq libraries represent the genetic response of distinct types of cortical interneurons to altered sensory experience. Overall design: To explore how sensory experience affects gene expression, we examined this process in the visual cortex of adult mice that were housed in standard conditions, in complete darkness (i.e. dark-housed), or dark-housed and then exposed to light for increasing amounts of time. We generated mice that were heterozygous for alleles of either Emx-,Gad2-,Sst-,Vip- or Pv-Cre, and were also heterozygous for the Rpl22-HA (RiboTag) allele, which expresses an HA-tagged ribosomal protein specifically in Cre-expressing neurons. We performed RNA-Seq on RNA isolated from the dark-housed/light-exposed RiboTag-mice; Experiments were done in 3 biological replicates and the visual cortices of 3 mice were pooled per sample at each time-point and for each Cre line.
Publication Title
Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Juvenile pilocytic astrocytoma (JPA) is one of the most common brain tumors in children. The expression profiles of 21 JPAs, determined using Affymetrix GeneChip U133A, were compared with subjects with normal cerebella. The genes involved in neurogenesis, cell adhesion, synaptic transmission, central nervous system development, potassium ion transport, protein dephosphorylation, and cell differentiation were found to be significantly deregulated in JPA. These 21 JPAs were further clustered into two major groups by unsupervised hierarchical clustering using a set of 848 genes with high covariance (0.5-10). Supervised analysis with Significance Analysis of Microarrays software between these two potential subgroups identified a list of significant differentially expressed genes involved in cell adhesion, regulation of cell growth, cell motility, nerve ensheathment, and angiogenesis. Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic proteinpositively stained tumor cells may have a higher tendency to progress.
Publication Title
Expression analysis of juvenile pilocytic astrocytomas by oligonucleotide microarray reveals two potential subgroups.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2000
Description
A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the cerebrospinal fluid (CSF). To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) vs. fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system. Overall design: Two-factor design with two levels per factor and n=2 biological replicates. Lateral (telencephalic) and fourth (hindbrain) choroid plexus samples are paired in that they are isolated from the same brains.
Publication Title
Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray experiments were performed using FAC-sorted young photoreceptors to analyze their transcriptome in comparison to remaining retinal cells at same developmental stage and retinal progenitors.
Publication Title
Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
PQBP1 is a highly conserved protein closely related to neurodegenerative disorders. We identified PQBP1 as an important alternative splicing effector necessary for maintaining normal neuron functions in the brain. In order to explore PQBP1''s functions in alternative splicing regulation and neuronal activities, we systematically profiled the alternative splicing targets of PQBP1 in mouse embryonic cortical neurons by RNA-seq. The mRNAs whose alternative splicing are affected by PQBP1 showed tissue-specific functional enrichment especially in neurite outgrowth, with strong Gene Ontology (GO) enrichments for neuron projection development/morphogenesis, dendrite development and axonogenesis. PQBP1''s alternative splicing targets are also functionally enriched in RNA splicing, chromatin modification, and ARF signal transduction. Overall design: We applied RNA-seq to compare the transcriptomes of mock and PQBP1 knockdown mouse embryonic cortical neuron samples.
Publication Title
PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Loss of the tumor suppressor CHD5 frequently occurs during neuroblastoma progression.
Publication Title
The chromatin remodeling factor CHD5 is a transcriptional repressor of WEE1.
Sample Metadata Fields
Specimen part, Cell line
View Samples