IRE1a is a critical modulator of the unfolded protein response. Its RNAse activity generates the mature transcript for the XBP1 transcription factor and also degrades other ER associated mRNAs in a process termed Regulated IRE1a Dependent mRNA Decay or RIDD. To determine if IRE1a is critical in the response to oncogenic Ras we used ShRNA to knockdown Ire1a or Xbp1 in primary mouse epidermal keratinocytes transduced with a v-HRAS retrovirus.
ER stress and distinct outputs of the IRE1α RNase control proliferation and senescence in response to oncogenic Ras.
No sample metadata fields
View SamplesDifferential gene expression profiles were observed in response to Hras in either wild-type or Ppar-beta null primary keratinocytes and differentail gene edxpression profiles by GW0742 were only found in wild-type keratinocytes.
Peroxisome proliferator-activated receptor β/δ cross talks with E2F and attenuates mitosis in HRAS-expressing cells.
Specimen part
View SamplesGraft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with FR104 monotherapy and FR104/Sirolimus combination therapy
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T<sub>reg</sub> reconstitution after transplant.
Specimen part, Subject
View SamplesGraft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with KY1005 monotherapy and KY1005/Sirolimus combination therapy
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T<sub>reg</sub> reconstitution after transplant.
No sample metadata fields
View SamplesWe report our results of RNA-seq analysis on freshly isolated, sorted subsets of cytotoxic lymphocytes Overall design: RNA was isolated from sorted cells. Libraries were created using standard Illumina reagents and analyzed using a HiSeq2500.
ARID5B regulates metabolic programming in human adaptive NK cells.
Specimen part, Subject
View SamplesTo gain comprehensive insight into the OGT-dependent transcriptional program in Treg cells, we performed RNA-sequencing of isolated YFP+ Treg cells from Foxp3YFP-Cre/wtOgtwt/fl and healthy Foxp3YFP-Cre/wtOgtfl/fl females to avoid secondary changes in gene expression caused by inflammation. We were able to identify 269 differentially expressed genes including 154 downregulated and 115 upregulated with p values less than 0.01, OGT-deficient Treg cells had impaired suppressive function and attenuated IL2/STAT5 signaling pathway. Overall design: Examination of the function of OGT in Treg cells
The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
Specimen part, Cell line, Subject
View SamplesGraft-versus-host disease (GVHD) is the most serious complication of allogeneic hematopoietic cell transplantation. Notch signals delivered during the first 48 hours after transplantation drive proinflammatory cytokine production in conventional T cells (Tconv) and inhibit expansion of regulatory T cells (Tregs). Short-term Notch inhibition induces long-term GVHD protection. However, it remains unknown whether Notch blockade blunts GVHD through its effects on Tconv, Tregs, or both, and what early Notch-regulated molecular events occur in alloantigen-specific T cells. To address these questions, we engineered T cell grafts to achieve selective Notch blockade in Tconv vs. Tregs and evaluated their capacity to trigger GVHD in mice. Notch blockade in Tconv was essential for GVHD protection, as GVHD severity was similar in recipients of wild-type Tconv combined with Notch-deprived vs. wild-type Tregs. To identify the impact of Notch signaling on the earliest steps of T cell activation in vivo, we established a new acute GVHD model mediated by clonal alloantigen-specific 4C CD4+ Tconv. Notch-deprived 4C T cells had preserved early steps of activation, IL-2 production, proliferation, and T helper polarization. In contrast, Notch inhibition dampened IFN-? and IL-17 production, diminished mTORC1 and ERK1/2 activation, and impaired transcription of a subset of Myc-regulated genes. The distinct Notch-regulated signature had minimal overlap with known Notch targets in T cell leukemia and developing T cells, highlighting the specific impact of Notch signaling in mature T cells. Our findings uncover a unique molecular program associated with pathogenic effects of Notch in T cells at the earliest stages of GVHD. Overall design: 4 samples per cohort (Notch blockade using Dll1/4 neutralizing antibodies vs isotype control antibodies - GD) were analyzed. Additional 4 samples contained 4C T cells retrieved from syngeneic recipients.
Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4<sup>+</sup> T Cells in Graft-versus-Host Disease.
Specimen part, Cell line, Treatment, Subject
View SamplesNatural killer (NK) cells can be divided into phenotypic subsets based on the expression of receptors that bind self-MHC-I molecules with differing affinities; a concept termed licensing or education. Here we show that NK cell subsets exhibit markedly different migratory, effector, and immunoregulatory functions on dendritic cells and antigen-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells preferentially trafficked to draining lymph nodes and produced GM-CSF, which promoted the expansion and activation of dendritic cells, and ultimately resulted in sustained antigen-specific CD8+ T cell responses. In contrast, licensed NK cells preferentially migrated to infected parenchymal tissues and produced greater levels of interferon- (IFN-). Importantly, human NK cell subsets exhibited similar phenotypic characteristics and patterns of cytokine production. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset in inflamed tissues and the latter as modulators of adaptive immunity helping to prime immune responses in draining lymph nodes.
Licensing delineates helper and effector NK cell subsets during viral infection.
Specimen part
View SamplesS288C was transformed with plasmids expressing the GCN5 F221A mutant at varying levels. We sought to examine the global impact on gene expression
Linking yeast Gcn5p catalytic function and gene regulation using a quantitative, graded dominant mutant approach.
No sample metadata fields
View SamplesThe aim of this experiment is to determine Hhex targets in the presence and absence of Myc.
Growth-promoting and tumourigenic activity of c-Myc is suppressed by Hhex.
Cell line
View Samples