OT-1 Transgenic CD8 T-cells were isolated from spleens of WT, PKC theta KO, and p50 cRel DKO mice. The T-cells were either cultured with non-pulsed DC (WT only and signified as "WT - UN") or with BMDCs pulsed with the OVA peptide SIINFEKL (N4) (WT, PKC theta KO, and p50 cRel DKO and signified as 'genotype - N4') at a ratio of 1:10 (DC:T-cell) for 18 hours. DCs then were depleted from the culture and RNA was made from the T-cells to measure gene expression at the early / late stage of T-cell activation
NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation.
Specimen part
View SamplesA greater understanding of the molecular pathways that underpin the unique human hematopoietic stem and progenitor cell (HSPC) self-renewal program will improve strategies to expand these critical cell types for regenerative therapies. The post-transcriptional mechanisms guiding HSPC fate during ex vivo expansion have not been closely investigated. Using shRNA-mediated knockdown, we show that the RNA-binding protein (RBP) Musashi-2 (MSI2) is required for human HSPC self-renewal. Conversely, when overexpressed, MSI2 induces multiple pro-self-renewal phenotypes, including significant ex vivo expansion of short- and long-term repopulating cells through direct attenuation of aryl hydrocarbon receptor (AHR) signaling. Using a global analysis of MSI2-RNA interactions, we determined that MSI2 post-transcriptionally downregulates canonical AHR pathway components in cord blood HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and provides evidence that manipulating such networks can provide a novel means to enhance the regenerative potential of human HSPCs expanded ex vivo. Overall design: 4 samples were used for RNA-seq (4 biological duplicate) including 2 sets of control samples (irrelvant shRNA kncok-downs)
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.
No sample metadata fields
View SamplesThe human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study, we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells.
Characterization and isolation of stem cell-enriched human hair follicle bulge cells.
No sample metadata fields
View SamplesMicroRNA-155 (miR-155) is upregulated in primary effector CD8 T cells but is expressed at low amounts in nave cells. Anti-viral CD8 T cell responses and viral clearance were impaired in miR-155 deficient (bic-/-) mice, and this defect was intrinsic to CD8 T cells, as adoptively transferred bic-/- CD8 T cells generated greatly reduced primary and memory responses during infection. To understand the mechanism by which miR-155 regulates CD8 T cell activation, we analyzed the gene expression profiles of naive and in vitro activated wild-type and bic-/- CD8 T cells.
The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.
Specimen part
View SamplesExpression profile of FLA2 (highest LSC frequency) and FLB1 (lowest LSC frequency) leukemias.
A role for GPx3 in activity of normal and leukemia stem cells.
Specimen part
View SamplesEffect of NF-kB inhibition and activation on gene expression in mouse and human lung cancer cell-lines.
Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance.
Cell line
View SamplestRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and its distribution is nutrient-dependent. At least three members of -importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates translation of particular transcripts
Genome-wide investigation of the role of the tRNA nuclear-cytoplasmic trafficking pathway in regulation of the yeast Saccharomyces cerevisiae transcriptome and proteome.
Treatment
View SamplesElevated fructose consumption has been associated with metabolic and renal diseases. It is controversial whether kidney problems are a result of systemic metabolic disease or stem, at least in part, from changes due to local fructose metabolism. To study the short-term effect of fructose on genetic programs in renal proximal tubules, the diet for rats in experimental groups was supplemented for 7 days with 20% fructose in the drinking water. Two sets of 8 rats each on different baseline rodent diets were used in this study. 4 animals of each set received fructose in the drinking water while the other 4 served as controls. Animals were sacrificed after the experimental period of 7 days and slices of superficial kidney cortex were used for total RNA extraction. The RNA was analyzed with Affymetrix RaGene-2_0-st.
Transcriptome signature for dietary fructose-specific changes in rat renal cortex: A quantitative approach to physiological relevance.
Sex, Age, Specimen part
View SamplesWe assessed vastus lateralis muscle gene expression levels of 12 women with the metabolic syndrome before and after a 6 month exercise training program
Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesThe goal of this experiment was to compare the genes expressed in malignant peripheral nerve sheath tumors (MPNSTs) that arise in zebrafish as a result of homozygous mutation of the p53 gene or heterozygous mutation of several different ribosomal protein (rp) mutations. Since MPNSTs arise very rarely in wild type zebrafish, it seemed a possibility that p53 and rps may in fact be functioning in similar pathways. The tumors arising from the different mutations had been previously classified as similar by histology, thus the goal of the array experiments was to establish if any molecular signatures could be found that could delineate the p53 from the rp MPNSTs.
Loss of p53 synthesis in zebrafish tumors with ribosomal protein gene mutations.
No sample metadata fields
View Samples