Our results introduce interleukin (IL)-11 as a new cytokine that may play a role in the development of the autoimmune response in patients with relapsing remitting multiple sclerosis (RR MS). IL-11 was found to be the highest up-regulated cytokine in the serum and cerebrospinal fluid (CSF) from patients with clinically isolated syndrome (CIS) suggestive of MS. It was also increased in the serum and CSF of patients with clinically definitive RRMS and during the clinical relapses of the disease. CD4+ cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11+CD4+ cells is significantly increased in CIS patients in comparison to healthy controls (HCs). Furthermore, we have identified IL-11 as a new Th17-promoting cytokine. IL-11 induces a differentiation of nave CD4+ T cells into Th17 cells, as well as Th17 memory cell expansion, characterized by secretion of IL-17A, IL-17F, IL-21 and IL-22. Since the Th17 cytokines IL-17F, IL-21 and TNF- induced differentiation of nave cells in the IL-11-secreting CD4+ cells, we propose that cross-talk between IL-11+CD4+ and Th17-cells may play a role in the initiation and propagation of the autoimmune response in RRMS.
IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.
Specimen part
View SamplesGene expression analysis of T-cell acute lymphoblastic leukemia blast cells from either control mice or Dnmt3a knockout mice carrying a Notch1 Intracellular Domain (NICD) retrovirus Overall design: Comparison of gene expression between control and Dnmt3a-KO NICD-driven T-ALL
Dnmt3a regulates T-cell development and suppresses T-ALL transformation.
Specimen part, Cell line, Subject
View SamplesResponse to allergen was studied in bronchial epithelial cell line H292. Cells were cultured and subsequently exposed to House dust mite or vessel (saline)
Allergen induced gene expression of airway epithelial cells shows a possible role for TNF-alpha.
No sample metadata fields
View SamplesAccumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis- multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/ Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.
eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.
Specimen part, Cell line, Treatment
View SamplesWe measured mRNA abundance in the embryogenic tissue of 150 recombinant Steptoe x Morex doubled-haploid lines (no replicates) and in parental genotypes, Steptoe and Morex, 3 replicates each, total 156 chips.
SFP genotyping from affymetrix arrays is robust but largely detects cis-acting expression regulators.
Age, Specimen part, Time
View SamplesShort-term bed rest is used to simulate muscle disuse in humans. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects. Identifying muscle transcriptional events in response to bed rest and age-related differences will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. Skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aide in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. Short-term muscle disuse is also characterized by skeletal muscle insulin resistance, though this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known, and delineated by age. High Susceptibility participants were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1). Overall design: RNA was isolated and sequenced from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9) and OLD (N=18) men and women before and after five days of bed rest. Sequencing libraries (18 pM) were chemically denatured and applied to an Illumina TruSeq v3 single read flowcell using an Illumina cBot. Hybridized molecules were clonally amplified and annealed to sequencing primers with reagents from an Illumina TruSeq SR Cluster Kit v3-cBot-HS (GD-401-3001). Following transfer of the flowcell to an Illumina HiSeq 2500 instrument (HCS v2.0.12 and RTA v1.17.21.3), a 50 cycle single read sequence run was performed using TruSeq SBS v3 sequencing reagents (FC-401-3002). The design formula was constructed by following the section on group-specific condition effects, individuals nested within groups in the DESeq2 vignette. The design included age + age:nested + age:time to test for differences in bed rest in old subjects, young subjects and the interaction, in this case if bed rest effects are different between the two age groups (where age is young or old, nested is patient number nested by age and time is pre- or post-bed rest). A similar design was used to determine susceptibility to disuse-induced insulin resistance, where “susceptibility” took the place of “age”.
Disuse-induced insulin resistance susceptibility coincides with a dysregulated skeletal muscle metabolic transcriptome.
Sex, Specimen part, Subject, Time
View SamplesComparison of mRNA accumulation in segregating doubled haploid barley lines ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, . The equivalent experiment is BB21 at PLEXdb.]
SFP genotyping from affymetrix arrays is robust but largely detects cis-acting expression regulators.
Specimen part
View SamplesDicer1 loss in the aP2-lineage leads to the development of aggressive and highly penetrant angiosarcomas independent of other oncogenes or tumor suppressor loss
Biallelic <i>Dicer1</i> Loss Mediated by <i>aP2-Cre</i> Drives Angiosarcoma.
Specimen part
View SamplesWe intended to investigate effects of mmu-miR-15a-3p on gene expression in mice
Large-scale screening identifies a novel microRNA, miR-15a-3p, which induces apoptosis in human cancer cell lines.
Specimen part
View SamplesTumor ecosystems are composed of multiple cell types that communicate by ligand-receptor interactions. Targeting ligand-receptor interactions, for instance with immune check-point inhibitors, can provide significant benefit for patients. However, our knowledge of which interactions occur in a tumor and how these interactions affect outcome is still limited. We present an approach to characterize communication by ligand-receptor interactions across all cell types in a microenvironment using single-cell RNA sequencing. We apply this approach to identify and compare ligand-receptor interactions present in six syngeneic mouse tumor models. To identify interactions potentially associated with outcome, we regress interactions against phenotypic measurements of tumor growth rate. In addition, we quantify ligand-receptor interactions between T-cell subsets and their relation to immune infiltration using a publicly available human melanoma data-set. Overall, this approach provides a tool for studying cell-cell interactions, their variability across tumors, and their relationship to outcome. Overall design: We used three different types of immuno-competent inbred mouse strains: BALB/c, and A/J z. All animals enrolled in our study were 6-8 weeks old female mice that were housed in vivarium under specific pathogen free conditions in cages of up to 5 animals and receiving special rodent diet (Teklad). We implanted two mice for each syngeneic model resulting in a total of 12 samples. Each mouse tumor was harvested when the tumor size reached 100 – 200 mm3. Each sample was minced and digested with reagents from Mouse Tumor Dissociation Kit (Miltenyi) according to the manufacturer's instructions. Cells were resuspended at 2x105 cells/mL in PBS-0.04% BSA. Each sample was processed individually and run in technical duplicates. For each sample (except CT26 and MC-38) one replicate was enriched for CD45 positive cells. Live CD45 positive cells were sorted with BD Aria after staining with FITC-CD45 (Biolegend) and 7-AAD. Single cell suspensions of all samples were resuspended in PBS-0.04% BSA at 5x105 cells/mL and barcoded with a 10x Chromium Controller (10x Genomics). In total, this procedure resulted in 24 samples.
Analysis of Single-Cell RNA-Seq Identifies Cell-Cell Communication Associated with Tumor Characteristics.
Cell line, Subject
View Samples