Filters
Technology
Platform
SRP174055
Homo sapiens
14 Downloadable Samples
Illumina HiSeq 2500
Description
Lung adenocarcinoma (LUAD)-derived oncogenic Wnts increase cancer cell proliferative/stemness potential, but whether they also impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. Wnt1 correlated strongly with tolerogenic genes on the TCGA expression data. In another cohort, Wnt1 was inversely associated with T cell abundance. Altering Wnt1 expression profoundly affected growth of murine lung adenocarcinomas and this was strongly dependent on conventional dendritic cells and T cells. Mechanistically, Wnt1 lead to transcriptional silencing of CC/CXC chemokines in dendritic cells and T cell cross-tolerance. Wnt-target genes were up-regulated in human intratumoral dendritic cells and decreased upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-loaded nanoparticles as single therapy or part of combinatorial immunotherapies acted at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 enhances adaptive immune rejection of lung adenocarcinomas and highlight its potential targeting as a novel therapeutic strategy Overall design: RNAseq data of two DC subsets of 4 patients with lung adenocarcinomas (LUADs).
Publication Title
Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Ion Torrent Proton
Description
This study showed that the oncogenic ligand Wnt1 silences chemokine genes in dendritic cells, leading to impaired cross-priming of T cells in lung adenocarcinoma. Blocking Wnt1 enhanced rejection of tumors by acting concomitantly at the cancer and immune cell level. Overall design: 3' RNA-Seq (QuantSeq) profiling of sorted cDCs populations from WNT1 overexpressing and control (Empty) lung tumors.
Publication Title
Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mast cells mediate malignant pleural effusion formation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Nave mast cells were cultured from murine bone marrow using incubation with IL-3 alone (samples 1-4) or IL-3 and KITL (samples 5-8).
Publication Title
Mast cells mediate malignant pleural effusion formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Functional characterization of AtWRKY72 using Arabidopsis T-DNA insertion lines showed that this gene is important for basal defense to root-knot nematode (RKN) and Hyaloperonospora parasitica arabidopsis (Hpa), but not several tested R gene-mediated defenses.To profile transcriptional reprogramming associated with AtWRKY72-dependent basal defense we used Affymetrix ATH1 GeneChips representing ~24,000 Arabidopsis genes. Three independent biological replicates were performed with Col-0, wrky72-1 and wrky72-2 plants at 96 hpt with HpaNoco2 or mock treatment. Using a false discovery rate of less than 0.05 we identified for each of these three lines genes that showed significant transcriptional changes in response to HpaNoco2 compared to the mock-treated controls. Identification of downstream targets of WRKY72 in Arabidopsis by this microarray suggests that WRKY72 uses a unique signaling pathway that involves AP2/ERF TFs independent of the ethylene signaling pathway.
Publication Title
WRKY72-type transcription factors contribute to basal immunity in tomato and Arabidopsis as well as gene-for-gene resistance mediated by the tomato R gene Mi-1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of human bone marrow derived stromal cells (MSCs) treated for 24 hours with or wihout 10ng/ml Fibroblast Growth Factor 2 (FGF2) MSCs were derived from 4 different healthy donors. Cells were expanded to passage 3-4. Then cells were treated with FGF-2. 24 hours later, total RNA was extracted (total 8 samples). Overall design: RNA was submitted to BGI Americas for RNAseq. Here, QC was performed using Agilent 2100. All samples had a RIN above 8.0. For preparation for library, mRNA was enriched by using the oligo (dT) magnetic beads. mRNA was enriched by using the oligo (dT) magnetic beads. mRNA was fragmented into short fragments (about 200bp) using a fragmentation buffer. Then the first strand of cDNA was synthesized by random hexamer-primer using the mRNA fragments as templates. Buffer, dNTSPs, RNase H and DNA polymerase I were added to synthesize the second strand. The double strand cDNA was purified with QiaQuick PCR extraction kit and washed with EB buffer for end repair and base A addition. Finally, sequencing adapters were ligated to the fragments. The fragments are purified by Agarose gel electrophoresis and enriched by PCR amplification. The library products are ready for sequencing analysis via 2 sE50 lanes in Illumina HiSeqâ„¢ 2000.
Publication Title
FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Biologic characterization of SB-559457 (SB), a non-peptidyl hydrazone class of thrombopoietin receptor (Mpl) agonist, revealed toxicity towards human leukemia cells. Anti-proliferative effects followed by significant, non-apoptotic, cell death within 72 hours occurred in 24/26 AML, 0/6 ALL, and 3/6 CML patient samples exposed to SB, but not recombinant human thrombopoietin (rhTpo), in liquid suspension culture. Further investigation revealed increased phosphorylation of p70S6/S6 kinases in SB, but not in rhTpo, treated cells. Expression profiling of cells exposed to SB vs rhTpo revealed statistically significant, ~2-fold changes in GAPDH and REDD1 gene expression, confirmed by QRT-PCR. These genes, induced in energy or hypoxia stressed cells, have been implicated in cell death pathways, and may provide important clues to the mechanism of SB induced, leukemic cell death. These results suggest that nonpeptidyl, hydrazone class Mpl agonists may be clinically useful anti-leukemic agents by virtue of their combined thrombopoietic and anti-leukemic effects.
Publication Title
A prototype nonpeptidyl, hydrazone class, thrombopoietin receptor agonist, SB-559457, is toxic to primary human myeloid leukemia cells.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple signaling pathways, structural proteins and transcription factors are involved in regulation of endothelial barrier function. The Forkhead protein FOXF1 is a key transcriptional regulator of lung embryonic development, and we use a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis and lung injury and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1 caused lung inflammation and edema, leading to respiratory insuffency and uniform mortality. Deletion of a single foxf1 allele was sufficient to increase susceptibility of heterozygous mice to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells of FOXF1 deletion indicated reduced expression for genes critical for maintance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, increased lung endothelial permeability, and the abundance of mRNA and protein for sphingosine 1 phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that FOXF1 directly bound to and induced the tanscriptional activity of the S1pr1 promoter. Pharmacological administratiion of S1P to injured pdgfb-iCreER/Foxf1 mice restored endothelial barrier function, decreased lung edema and improved survival. Thus, FOXF1 promotes normal lung homeostasis and lung repair, at least in part, by enhancing endothelial barrier function through transcriptional activation of the S1P/S1PR1/ signaling pathway. Overall design: RNA was isolated and pooled from the lungs of multiple mice with either the Foxf1 floxed alleles alone or Pdgfb-iCreER Foxf1 floxed mice.
Publication Title
FOXF1 maintains endothelial barrier function and prevents edema after lung injury.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes.
Publication Title
The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this data set we include expression data from human CD4+ T cells isolated on day 0, 6, 11 and 24 follow anti-CD3/anti-CD28 magnetic bead stimulation and chimeric antigen receptor transduction.
Publication Title
Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells.
Sample Metadata Fields
Specimen part
View Samples