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GSE22443
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The expansion, trafficking and functional effectiveness of adoptively transferred CD8+ T-cells play a critical role in mediating effective anti-tumor immunity. However, the mechanisms which program the highly proliferative and functional state of CD8+ T-cells are not completely understood. We hypothesized that IL-12, a cytokine commonly induced by TLR activation, could enhance T-cell priming by altering responsiveness to antigen and cytokines. Priming of tumor specific CD8+ T-cells in the presence of IL-12 induced the acquisition of a 'polyfunctional' effector response and increased the generation of memory cells. Moreover, IL-12 priming also promoted high levels of the IL-2 receptor alpha-chain (CD25) and robust IL-2 mediated activation of STAT5. This sensitivity to IL-2 translated into enhanced in vivo proliferation of adoptively transferred CD8+ T-cells. Furthermore, real-time, in vivo imaging of T-cell trafficking confirmed the ability of IL-12 priming to drive in vivo proliferation. IL-12 priming enhanced the anti-tumor function of adoptively transferred cells by reducing established subcutaneous tumor burden, and significantly increasing survival in an established intracranial tumor model. Finally, IL-12 priming of human PBMCs generates tumor specific T-cells phenotypically and functionally similar to IL-12 primed Pmel-1 T-cells. These results highlight IL-12 as an important mediator of CD8+ T-cell effector function and anti-tumor immunity.
Publication Title
Enhanced sensitivity to IL-2 signaling regulates the clinical responsiveness of IL-12-primed CD8(+) T cells in a melanoma model.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
NextSeq 500
Description
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was confirmed using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 expression without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to separate stem and progenitor cells, RNA-seq identified unique gene signatures for the separate populations which may serve as biomarkers. Pathways enrichment in stem cells identified ribosome biogenesis and membrane estrogen-receptor signaling with NF?B signaling enriched in progenitors and these were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified cancer stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Overall design: Comparing RNA-seq gene profiles in label-retaining prostate stem cells and non-retaining progenitor cells
Publication Title
Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Maternal IL10 deficiency elevates susceptibility to fetal loss induced by the model Toll-like receptor agonist lipopolysaccharide, but the mechanisms are not well elucidated. Here we show that Il10 null mutant (Il10-/-) mice exhibit altered local T cell responses in pregnancy, exhibiting pronounced hyperplasia in para-aortic lymph nodes draining the uterus with >6-fold increased CD4+ and CD8+ T cells compared with wild-type controls. Amongst these CD4+ cells, Foxp3+ Treg cells were substantially enriched, with 11-fold higher numbers at day 9.5 post coitum (pc). Lymph node hypertrophy in Il10-/- mice was associated with more activated phenotypes in dendritic cells and macrophages, with elevated expression of MHCII, scavenger receptor and CD80. Affymetrix microarray revealed an altered transcriptional profile in Treg cells from pregnant Il10-/- mice, with elevated expression of Ctse (cathepsin E), Il1r1, Il12rb2 and Ifng. In vitro, Il10-/- Treg cells showed reduced steady state Foxp3 expression, and polyclonal stimulation caused greater loss of Foxp3 and reduced capacity to suppress IL17 in CD4+Foxp3- T cells. We conclude that despite a substantially expanded Treg cell pool, diminished stability of Treg cells, increased numbers of effector T cells, and altered phenotypes in dendritic cells and macrophages in pregnancy all potentially confer vulnerability to inflammation-induced fetal loss in Il10-/- mice. These findings suggest a pivotal role for IL10 in facilitating robust immune protection of the fetus from inflammatory challenge and suggest IL10 deficiency could contribute to human gestational disorders where altered T cell responses are implicated.
Publication Title
Unstable Foxp3+ regulatory T cells and altered dendritic cells are associated with lipopolysaccharide-induced fetal loss in pregnant interleukin 10-deficient mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression was influenced most by the tissue source, followed by culture methodology, next by location where the cells were cultured and lastly the donor variability.
Publication Title
The impact of cell source, culture methodology, culture location, and individual donors on gene expression profiles of bone marrow-derived and adipose-derived stromal cells.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To determine the modulation of gene expression of C57BL/6 and DBA/2 BMDLs in the presence of living intracellular Leishmania amazonensis amastigotes
Publication Title
Distinct transcriptional signatures of bone marrow-derived C57BL/6 and DBA/2 dendritic leucocytes hosting live Leishmania amazonensis amastigotes.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 15 Downloadable Samples
- Illumina HiSeq 1500
Description
UV-B radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibits maize leaf growth without causing any other visible stress symptoms, including accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth is a consequence of a reduction in cell production, and a shortened growth zone (GZ) in UV-B irradiated leaves. To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including Growth Regulating Factors (GRFs) and transcripts for proteins participating in different hormone pathways. Overall design: Factorial design with two factors: Treatment (control vs UV-B) x Zone I (0-1cm from base of the leaf), 2 (1-2cm from base of the leaf) and 3 (2-3cm from base of the leaf), 3 replicates
Publication Title
UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In mammals, resident dermal macrophages (Ms) are subverted by Leishmania (L.) amazonensis amastigotes as host cells permissive for parasite multiplication. These Leishmania are living within a communal parasitophorous vacuole (PV) and are expected to trigger unique M transcriptional signatures. We performed a transcription profiling of mouse Ms harboring amastigotes to get insights into their reprogramming as host cells for parasite multiplication. BALB/c mouse bone marrow-derived Ms were either loaded or not with four amastigotes on average. Twenty four hours later, when amastigotes multiply, total RNA from M cultures was prepared, amplified and hybridized onto Affymetrix Mouse430_2 GeneChips. The outcome recorded a total of 1,248 probe-sets showing significant differential expression. Comparable fold-change values for a handful of genes were obtained between Affymetrix technology and the more sensitive RTqPCR method. Ingenuity Pathway Analysis software pinpointed the up-regulation of the sterol biosynthesis pathway (P-value = 1.31e-02) involving several genes (1.95 to 4.30 fold-change values), and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signaling. Our findings suggest that amastigotes exploit the M lipid and polyamine pathways to multiply efficiently, and induce a counter-inflammatory environment to expand their dermis niche.
Publication Title
Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 35 Downloadable Samples
- Illumina HiSeq 2000
Description
We studied two growth phases- proliferation, and expansion in first pair of leaves in Arabidosis using two different overexpression lines of PID gene. Ectopic expression of PID lead to small rosette and leaf phenotype. Overall design: We used first pair of leaves from proliferation ( 9 DAS-days after stratification) and expansion (16 DAS) stage from wild type Col-0 ecotype, 35S::PID10, 35S::PID21. Three genotype, three biological replicates, two time points (=18 sample). Experiment repeated twice generating two reads in two lanes i.e. L001 & L002 for each sample. Results calculated after combining reads from both lanes (=18x2=36 raw files; 2 for each sample)
Publication Title
Perturbation of Auxin Homeostasis and Signaling by <i>PINOID</i> Overexpression Induces Stress Responses in Arabidopsis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To determine the modulation of gene expression of mouse BMDCs in the presence of living intracellular Leishmania amazonensis amastigotes
Publication Title
Sorting of Leishmania-bearing dendritic cells reveals subtle parasite-induced modulation of host-cell gene expression.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To determine the modulation of gene expression of mouse BMDCs in the presence of living intracellular Leishmania amazonensis amastigotes at 24 hr post infection.
Publication Title
<i>Leishmania amazonensis</i> Subverts the Transcription Factor Landscape in Dendritic Cells to Avoid Inflammasome Activation and Stall Maturation.
Sample Metadata Fields
Specimen part, Time
View Samples