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SRP100848
Mus musculus
49 Downloadable Samples
Illumina HiSeq 2000
Description
The EZH2 histone methyltransferase is required for B cells to form germinal centers (GCs). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21Cip1). Deletion of Cdkn1a rescued the GC reaction in Ezh2 knockout mice. To study the effects of EZH2 in primary GC B cells we generated and validated a 3D B cell follicular organoid system that mimics the endogenous GC reaction. Using this system we found that depletion of EZH2 suppressed G1 to S phase transition of GC B cells in a Cdkn1a dependent manner. GC B cells of Cdkn1a;Ezh2 double knockout mice exhibited high levels of phospho Rb, indicating that loss of Cdkn1a allows progression of cell cycle. Moreover, we show that the transcription factor E2F1 plays a major role in inducing EZH2 upregulation during the GC reaction. E2F1 deficient mice manifest impaired GC responses, which was rescued by restoring EZH2 expression, thus defining a positive feedback loop whereby EZH2 controls GC B cell proliferation by suppressing CDKN1A, allowing cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1. Overall design: gene expression profiles of murine B cells
Publication Title
EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inhibition of neuronal nitric oxide synthase activity promotes migration of human-induced pluripotent stem cell-derived neural stem cells toward cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neural stem cells can migrate towards tumors of both neural and non-neural origins, which is crucial for the success in treating disseminated tumors. Although the understanding of the molecular mechanisms underlying NSC tumor tropism is limited, it has been noted that several cytokines, growth factors and receptors direct the migration in vitro. A proper understanding of the basic molecular mechanisms of NSC migration towards tumors, especially identification of key cellular regulators of the migration, will have important implications in improving the effectiveness of engineering and employing NSCs as tumor therapy agents.
Publication Title
Inhibition of neuronal nitric oxide synthase activity promotes migration of human-induced pluripotent stem cell-derived neural stem cells toward cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neural stem cells can migrate towards tumors of both neural and non-neural origins, which is crucial for the success in treating disseminated tumors. Although the understanding of the molecular mechanisms underlying NSC tumor tropism is limited, it has been noted that several cytokines, growth factors and receptors direct the migration in vitro. A proper understanding of the basic molecular mechanisms of NSC migration towards tumors, especially identification of key cellular regulators of the migration, will have important implications in improving the effectiveness of engineering and employing NSCs as tumor therapy agents.
Publication Title
Inhibition of neuronal nitric oxide synthase activity promotes migration of human-induced pluripotent stem cell-derived neural stem cells toward cancer cells.
Sample Metadata Fields
Specimen part
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
- 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