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GSE10908
Mus musculus
26 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the -secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity.
Publication Title
Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice.
Sample Metadata Fields
Sex, Age
View Samples- 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
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Microglia are brain immune cells that constantly survey their environment to maintain homeostasis. Enhanced microglial reactivity and proliferation are typical hallmarks of neurodegenerative diseases. Whether specific disease-linked microglial subsets exist during the entire course of neurodegeneration, including the recovery phase, is currently unclear. Taking a single-cell RNA-sequencing approach in a susceptibility gene-free model of nerve injury, we identified a microglial subpopulation that upon acute neurodegeneration shares a conserved gene regulatory profile compared to previously reported chronic and destructive neurodegeneration transgenic mouse models. Our data also revealed rapid shifts in gene regulation that defined microglial subsets at peak and resolution of neurodegeneration. Finally, our discovery of a unique transient microglial subpopulation at the onset of recovery may provide novel targets for modulating microglia-mediated restoration of brain health. Overall design: scRNA-Seq was performed on microglial cells isolated from the ipsilateral and contralateral ventral pons of CX3CR1GFP/wt mice that underwent unilateral facial nerve axotomy at 12 weeks of age. The contralateral ventral pons of un-operated 12-week-old CX3CR1GFP/wt was used as baseline control (Day 0 post nerve transection) for the analysis. Three replicates were used per time point (Day 0, 7 and 30 post axotomy). mCEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016, Herman et al. 2018).
Publication Title
Unique microglia recovery population revealed by single-cell RNAseq following neurodegeneration.
Sample Metadata Fields
Age, Specimen part, Cell line, 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- Saccharomyces cerevisiae
- 70 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
We construced combinations of genetic deletions to infer genetic interactions in genomic expression data.
Publication Title
Prediction of phenotype and gene expression for combinations of mutations.
Sample Metadata Fields
No sample metadata fields
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
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The -amyloid precursor protein APP and the related APLPs, undergo complex proteolytic processing giving rise to several fragments. Whereas it is well established that A accumulation is a central trigger for Alzheimer disease (AD), the physiological role of APP family members and their diverse proteolytic products is still largely unknown. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain AICD, functions as a transciptional regulator in heterologous reporter assays, although its role for endogenous gene regulation has remained controversial. To gain further insight into the molecular changes associated with knockout phenotypes and to elucidate the physiological functions of APP family members including their proposed role as transcriptional regulators we performed a DNA microarray transcriptome profiling of the frontal cortex of adult wild type, APP-/-, APLP2-/- and APPs knockin (KI) mice, APP/, expressing solely the secreted APPs ectodomain. Biological pathways affected by the lack of APP family members included regulation of neurogenesis, regulation of transcription and regulation of neuron projection development. Comparative analysis of transcriptome changes and qPCR validation identified co-regulated gene sets. Interestingly, these included heat shock proteins and plasticity related genes that were down-regulated in knock-out cortices. In contrast, we failed to detect significant differences in expression of previously proposed AICD target genes including Bace1, Kai1, Gsk3b, p53, Tip60 and Vglut2. Only Egfr was slightly up-regulated in APLP2-/- mice. Comparison of APP-/- and APP/ with wild-type mice revealed a high proportion of co-regulated genes indicating an important role of the C-terminus for cellular signaling. Finally, comparison of APLP2-/- on different genetic backgrounds revealed that background related transcriptome changes may dominate over changes due to the knockout of a single gene. Shared transcriptome profiles corroborated closely related physiological functions of APP family members in the adult central nervous system. As expression of proposed AICD target genes was not altered in adult cortex, this may indicate that these genes are not affected by lack of APP under resting conditions or only in a small subset of cells.
Publication Title
Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex.
Sample Metadata Fields
Sex, 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- 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