Filters
Technology
Platform
GSE43936
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PTEN is thought to play a critical role in T cell activation by negatively regulating the PI3K signaling pathway important for cellular activation, growth, and proliferation. T cells from mice in which PTEN was conditionally deleted in the thymus were reported to display CD28-independent IL-2 production and relative resistance to anergy induction. However, such observations could have stemmed from alterations in T cell development due to early deletion in thymocytes. To directly eliminate PTEN in post-thymic T cells, we utilized CAR Tg x PTENflox/flox mice which enabled gene deletion using a Cre adenovirus in vitro. Gene expression profiling revealed a small subset of induced genes that were augmented upon PTEN deletion and T cell stimulation. Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells. Nonetheless, PTEN inhibition may be a viable target for immune potentiation due to increased cytokine production by activated CD4+ cells.
Publication Title
Conditional deletion of PTEN in peripheral T cells augments TCR-mediated activation but does not abrogate CD28 dependency or prevent anergy induction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
T cell anergy is one of the mechanisms contributing to peripheral tolerance, particularly in the context of progressively growing tumors and in tolerogenic treatments promoting allograft acceptance. We recently reported that early growth response gene 2 (Egr2) is a critical transcription factor for the induction of anergy in vitro and in vivo, which was identified based on its ability to regulate the expression of inhibitory signaling molecules diacylglycerol kinase (DGK)-a and -z. We reasoned that other transcriptional targets of Egr2 might encode additional factors important for T cell anergy and immune regulation. Thus, we conducted two sets of genome-wide screens: gene expression profiling of wild type versus Egr2-deleted T cells treated under anergizing conditions, and a ChIP-Seq analysis to identify genes that bind Egr2 in anergic cells. Merging of these data sets revealed 49 targets that are directly regulated by Egr2. Among these are inhibitory signaling molecules previously reported to contribute to T cell anergy, but unexpectedly, also cell surface molecules and secreted factors, including lymphocyte-activation gene 3 (Lag3), Class-I-MHC-restricted T cell associated molecule (Crtam), Semaphorin 7A (Sema7A), and chemokine CCL1. These observations suggest that anergic T cells might not simply be functionally inert, and may have additional functional properties oriented towards other cellular components of the immune system.
Publication Title
Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Despite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling performed on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of 6 chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative RT-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be upregulated on human CD8+ effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8+ effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8+ effector T cells when implanted as xenografts in NOD/scid mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8+ T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of anti-tumor immunity.
Publication Title
Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
STING molecule has been reported to be important adaptor molecule for cytosolic DNA sensing. We investigated gene expression by cytosolic DNA stimulation using bone marrow derived dendritic cells. We comparared gene expression profile between WT and STING knock out BMDCs after cytosolic DNA stimulation.
Publication Title
STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
NextSeq 500
Description
We identified a subset of hepatocytes with high Telomerase Reverse transcriptase (Tert) that functions as the repopulating stem cells in homeostasis and injury. We performed RNA-Seq to reveal the differences of these cells and the other hepatocytes. Overall design: RNA mRNA profiles of TERT(High) and TERT (Low) hepatocytes from 2-month old mice were generated by deep sequencing, in triplicate, using Illumina platform.
Publication Title
Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 132 Downloadable Samples
- IlluminaHiSeq1500
Description
To understand better the factors contributing to keratoconus (KTCN), we used RNA sequencing to perform a transcriptome profile of human KTCN corneas. Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-ß, Hippo, and Wnt signaling pathways influencing corneal organization. We identified long noncoding RNAs (lncRNAs) and conducted a computational analysis of their potential functions, and found that lncRNAs regulated the processing and expression of the aforementioned genes. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN. Overall design: Transcription profiling of 25 KTCN and 25 non-KTCN corneas using RNA-Seq
Publication Title
Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.
Publication Title
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 23 Downloadable Samples
- Illumina HiSeq 2500
Description
Epigenetic inheritance contributes fundamentally to transgenerational physiology and fitness. Mechanistic understanding of RNA-mediated chromatin modification and transgenerational epigenetic inheritance, which in C. elegans can be triggered by exogenous double-stranded RNA (exo-dsRNA) or facilitated by endogenous small interfering RNAs (endo-siRNAs), has mainly been limited to the post-initiation phases of silencing. Indeed, the dynamic process by which nuclear RNAi engages a transcriptionally active target, before the repressive state is stably established, remains largely a mystery. Here we found that the onset of exo-dsRNA-induced nuclear RNAi is a transgenerational process, and that establishment requires SET-32, one of the three putative histone methyltransferases (HMTs) that are required for H3K9me3 deposition at the nuclear RNAi targets. We also performed multigenerational whole-genome analyses to examine the establishment of silencing at endogenous targets of germline nuclear RNAi. The nuclear Argonaute (AGO) protein HRDE-1 is essential for the maintenance of nuclear RNAi. Repairing a loss-of-function mutation in hrde-1 by CRISPR restored the silencing of endogenous targets in animals carrying wild type set-32. However, for numerous endogenous targets, repairing the hrde-1 mutation in a set-32;hrde-1 double mutant failed to restore their silencing states in up to 20 generations after the hrde-1 repair, using a similar genome editing approach. We found that despite a prominent role in the establishment of silencing, however, set-32 is completely dispensable for the maintenance of silencing once HRDE-1-dependent gene repression is established. Our study indicates that: 1) initiation and maintenance of siRNA-guided transcriptional repression are two distinct processes with different genetic requirements; and 2) the rate-limiting step of the establishment phase is a transgenerational, chromatin-based process. In addition, our study reveals a novel paradigm in which a heterochromatin factor primarily functions to promote the initiation of transgenerational silencing, expanding mechanistic understanding of the well-recognized role of heterochromatin in epigenetic maintenance. Overall design: 23 samples were analyzed using RNA-seq
Publication Title
C. elegans Heterochromatin Factor SET-32 Plays an Essential Role in Transgenerational Establishment of Nuclear RNAi-Mediated Epigenetic Silencing.
Sample Metadata Fields
Sex, Subject
View Samples