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SRP111386
Mus musculus
228 Downloadable Samples
Illumina HiSeq 2000
Description
Bone marrow-derived macrophages derived from C57Bl/6, Myd88-/- and Trif-/-, Ifnar-/-, Atm-/-, Sting-/-, Scid, Irf3-/-, Irf1-/-, p53-/-, Nrf2-/-mice were irradiated with 6Gray ioninzing radiation; C57Bl/6 macrophages were Irradiated in the presence of MAPK inhibitors or Reactive Oxygen Species Scavenger (N-Acetyl Cysteine), Two biological replicates were generated for each time point. RNA samples were collected at 0 (unirradiated), 0.5, 1, 2, 6, and 24h post irradiation except where ever mentioned. Overall design: Bone marrow-derived macrophages derived from C57Bl/6, Myd88-/- and Trif-/-, Ifnar-/-, Atm-/-, Sting-/-, Scid, Irf3-/-, Irf1-/-, p53-/-, Nrf2-/-mice were irradiated with 6Gray ioninzing radiation; C57Bl/6 macrophages were Irradiated in the presence of MAPK inhibitors or Reactive Oxygen Species Scavenger (N-Acetyl Cysteine), Two biological replicates were generated for each time point. RNA samples were collected at 0 (unirradiated), 0.5, 1, 2, 6, and 24h post irradiation except where ever mentioned.
Publication Title
Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 68 Downloadable Samples
- Illumina HiSeq 2000
Description
Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs) to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways have been shown to contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways responsible for the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, only two PRR pathways – the Toll-like receptor (TLR) and Stimulator of Interferon Gene (STING) pathways - were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated an inflammatory program, STING signaling activated an antiviral/type I interferon response, and both pathways contributed to a program linking innate and adaptive immunity. Only a small number of genes were induced in the absence of TLR or STING signaling, and these genes possessed a strong hypoxia signature. STING pathway activation required live S. aureus and was largely dependent on the DNA sensor cyclic guanosine-adenosine synthase (cGAS) recognition of S. aureus DNA. Interestingly, using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus, with TLR signaling being required for protective interleukin (IL)-1? and neutrophil recruitment and STING signaling having an opposite effect. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered byS. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus. Overall design: Files are labeled according to the figures in which they were used. Note, that many data files were used in multiple figures or figure panels. Files are labeled by genotype of macrophages (WT=wildtype; KO= StingGt/Gt; DKO=MyD88-/-TRIF-/-) and whether the macrophages were treated with live (Live) or heat killed (HK) or uninfected (zero hour). Labeling of time points is in the order of "minutes_replicate #." For example, "WT_HK_30_2" indicates that this is wild type mouse macrophages stimulated with heat killed bacteria at the 30-minute time point and is replicate number 2. Reads were converted into RPKM, and the RPKM for all replicates listed for a given time point were averaged to obtain the average RPKM that was used for figures and analyses. For samples listed as contributing to either figure 3 or supplemental figure 2, the replicates that do NOT end in either KO_analysis nor DKO analysis were used to determine induced genes in wild type macrophages. In contrast, the replicates that end in KO_analysis or DKO_analysis were used to determine dependence on either STING signaling or MyD88/TRIF signaling, respectively. If a replicate was used in the STING or MyD88/TRIF dependence analysis for both live and heat-killed S. aureus, "live_and_hk" was added after the dependence analysis it contributed to. Some 0h samples were used in both live and heat-killed analyses.
Publication Title
Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
NMuMG is an epithelial cell line that can be induced into EMT by TGF- treatment or MET by TGF- withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype.
Publication Title
Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin β4.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is known that natural killer (NK) cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of human NK cell subsets derived from peripheral blood, thymus and bone marrow. NK cell subpopulations were defined via expression of CD56 and CD16.
Publication Title
Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 226 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Purpose: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. Methods: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 158 TN tumors (54 AA) from The Cancer Genome Atlas (TCGA). Meta-analyses were performed to obtain summary estimates by combining TCGA and Detroit AA cohort results. Results: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR)=1.56, 95% confidence interval (CI) 1.31-1.86, nominal p=5.1x10-7, FDR p=0.014], SPIC [HR=1.47, 95%CI 1.26-1.73, nominal p=1.8x10-6, FDR p=0.022], and MIR4311 [HR=1.57, 95% CI 1.31-1.92, nominal p=2.5x10-5, FDR p=0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. Meta-analysis with TCGA data showed that CLCA2 and SPIC were associated with overall survival for TNBC among AA women. Conclusions: We identified three potential prognostic markers for TNBC in AA women, for which SPIC may be an AA-specific prognostic marker.
Publication Title
CLCA2 expression is associated with survival among African American women with triple negative breast cancer.
Sample Metadata Fields
Age, Treatment, Race
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Human Exon 1.0 ST Array (huex10st)
Description
We compared the transcriptome at gene expression level in hypoxic and normoxic conditions.
Publication Title
Continuous hypoxic culturing of human embryonic stem cells enhances SSEA-3 and MYC levels.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD138+ B220- plasma cells were sorted from bone marrow and B220+ CD23+ mature follicular B cells were sorted from the spleens. Plasma cells were sorted from C57BL/6 mice 7 days after boosting with antigen, with mice first primed with an i.p. injection of KLH/IFA followed by boost at day 21 with KLH/PBS i.p. Mature B cells were sorted from antigen-nave C57BL/6 mice.
Publication Title
Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice have been treated with NOX-A12. Whole BM cells have been harvested, RNA isolated, and gene expression profiling was performed on cDNA using Mouse Genome 430 2.0 array. Untreated mice have been used as control.
Publication Title
SDF-1 inhibition targets the bone marrow niche for cancer therapy.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- IlluminaHiSeq2500
Description
Estrogen receptor a (ERa) is an important biomarker of breast cancer severity and a common therapeutic target. Recent studies have demonstrated that in addition to its role in promoting proliferation, ERa also protects tumors against metastatic transformation. Current therapeutics antagonize ERa and interfere with both beneficial and detrimental signaling pathways stimulated by ERa. The goal of this study is to uncover the dynamics of coding and non-coding RNA (microRNA) expression in response to estrogen stimulation and identify potential therapeutic targets that more specifically inhibit ERa-stimulated growth and survival pathways without interfering with its protective features. To achieve this, we exposed MCF7 cells (an estrogen receptor positive model cell line for breast cancer) to estrogen and prepared a time course of paired mRNA and miRNA sequencing libraries at ten time points throughout the first 24 hours of the response to estrogen. From these data, we identified three primary expression trends—transient, induced, and repressed—that were each enriched for genes with distinct cellular functions. Integrative analysis of paired mRNA and microRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217—an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that over-expression of miR-503 suppresses breast cancer cell proliferation. Overall, these data indicate that miR-503 acts as a potent estrogen-induced tumor suppressor microRNA that opposes cellular proliferation and has promise as a therapeutic for breast cancer. More generally, our work provides a systems-level framework for identifying functional interactions that shape the temporal dynamics of gene expression. Overall design: Quantification of mRNAs in MCF7 cells responding to estrogen following a period of estrogen starvation. Three independent biological replicates (30 samples: 3 replicates x 10 time points) of MCF7 cells were exposed to 10nM Estradiol for 0, 1, 2, 3, 4, 5, 6, 8, 12 , or 24 hours, and total RNA was extracted from the samples. Total RNA was used to generate paired RNA and miRNA sequencing. RNA libraries were prepared using an Illumina TruSeq stranded mRNA library preparation kit.
Publication Title
An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
AE-expressing murine BM cells treated with all-trans retinoic acid (ATRA) in semi-solid methycellulose-based cultures show an increase in self-renewal capacity whilst treatment with a specific RARa agonist NRX195183 reduces their clonogenicity. Gene expression analysis was performed to further investigate the molecular mechanisms underlying these observations. Upregulated gene sets were identified in the ATRA-treated AE BM cells.
Publication Title
ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples