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GSE44356
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
Publication Title
Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
To understand the role of LSD1 in B cell differentiation, mice with B cell conditional deletion of LSD1 were intravenously inoculated with LPS. After 3 days, B220+GL7-CD138- naïve B cells and CD138+ plasmablasts were FACS-sorted from the spleens and RNA-seq was performed to identify LSD1-target regulated genes. Overall design: RNA-seq on control or LSD1-deficient murine naïve B cells or plasmablasts.
Publication Title
The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast Differentiation.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Increasing evidence across malignancies suggests that infiltrating T cells at the site of disease are crucial to tumor control. We hypothesized that marrow-infiltrating immune populations play a critical role in response to donor lymphocyte infusion (DLI), an established and potentially curative immune therapy whose precise mechanism remains unknown. We therefore analyzed marrow-infiltrating immune populations in 29 patients (22 responders, 7 nonresponders) with relapsed chronic myelogenous leukemia who received CD4+ DLI in the pre-tyrosine kinase inhibitor era.
Publication Title
Reversal of in situ T-cell exhaustion during effective human antileukemia responses to donor lymphocyte infusion.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profile studies have identified an interferon signature in whole blood or mononuclear cell samples from patients with systemic lupus erythematosus. This study was designed to determine whether specific lymphocyte and myeloid subsets freshly isolated from the blood of systemic lupus erythematosus patients demonstrated unique gene expression profiles compared to subsets isolated from healthy controls.
Publication Title
Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina HiSeq 2000
Description
Introduction: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERa) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years. Conversely, activated mTORC1 provides negative feedback regulation of IGF signaling via insulin receptor substrate (IRS)-1/2 serine phosphorylation and subsequent proteasomal degradation. Thus, the IGF pathway may provide escape (e.g. de novo or acquired resistance) from mTORC1 inhibitors. It is therefore plausible that combined inhibition of mTORC1 and IGF-1R for select subsets of ER-positive breast cancer patients presents as a viable therapeutic option. Methods: Using hormone-sensitive breast cancer cells stably transfected with the aromatase gene (MCF-7/AC-1), works presented herein describe the in vitro and in vivo antitumor efficacy of the following compounds: dalotuzumab (DALO; “MK-0646”; anti-IGF-1R antibody), ridaforolimus (RIDA; “MK-8669”; mTORC1 small molecule inhibitor) and letrozole (“LET”, aromatase inhibitor). Results: With the exception of MK-0646, all single agent and combination treatment arms effectively inhibited xenograft tumor growth, albeit to varying degrees. Correlative tissue analyses revealed MK-0646 alone and in combination with LET induced insulin receptor alpha A (InsR-A) isoform upregulation (both mRNA and protein expression), thereby further supporting a triple therapy approach. Conclusion: These data provide preclinical rationalization towards the combined triple therapy of LET plus MK-0646 plus MK-8669 as an efficacious anti-tumor strategy for ER-positive breast tumors. Overall design: 46 samples, 28 days post treatment
Publication Title
Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Publication Title
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 100 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Rat Expression 230B Array (rae230b)
Description
5 strains of rat, WKY, spontaneously hypertensive rat (SHR) and 3 reciprocal congenic strains (WconSA, SconSA and SISA) were used to generate expression data across the genome using the Affymetrix rat genome chip set comprising the 230 A and 230 B chips. 5 animals from each strain were used. Expression data was determined for 2 ages: 6 week and 24 week with whole kidney RNA.
Publication Title
Genetic dissection of a blood pressure quantitative trait locus on rat chromosome 1 and gene expression analysis identifies SPON1 as a novel candidate hypertension gene.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2500
Description
B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cell division and is linked to DNA hypomethylation and gene regulation. Conversely, accumulation of DNA methylation in B cell differentiation is less apparent. To determine the role of de novo DNA methylation in B cell differentiation, the de novo DNA methyltransferases, Dnmt3a and Dnmt3b, were deleted in B cells resulting in phenotypically normal B cell development in the bone marrow, spleen and lymph nodes. However, upon immunologic challenge, mice deficient for Dnmt3a and Dnmt3b (Dnmt3-deficient) accumulated more antigen-specific B cells and bone marrow chimeras showed this was cell-autonomous. Additionally, a five-fold increase in splenic and bone marrow plasma cells was observed. Molecular analysis revealed that Dnmt3-deficient bone marrow plasma cells failed to repress gene expression to the same level as their Dnmt3ab-sufficient counterparts. This was coupled with a failure of Dnmt3-deficient germinal center B cells and plasma cells to gain and/or maintain DNA methylation at several thousand loci that were clustered in enhancers of genes that function in B cell activation and homing. Analysis of chromatin accessibility showed Dnmt3-deficient plasma cells had increased accessibility at several genes involved in hematopoiesis and B cell differentiation. These data show that de novo DNA methylation limits B cell activation, proliferation and differentiation, and support a model whereby DNA methylation represses the aberrant transcription of genes silenced in B cell differentiation to maintain plasma cell homeostasis. Overall design: Naïve lymph node B cells (B220+ GL7- Fas-), Phycoerythrin-specific germinal center B cells (B220+ GL7+ Fas+ PE+), and bone marrow plasma cells (CD138+) were compared between Cd19cre/wtDnmt3afl/flDnmt3bfl/fl (Dnmt3-deficient) and littermate control Cd19wt/wtDnmt3afl/flDnmt3bfl/fl (Dnmt3-sufficient) mice using RRBS, RNA-seq, and ATAC-seq. Naïve lymph node B cells were taken from naïve mice, whereas PE-specific germinal center B cells and bone marrow plasma cells were isolated from mice that had been immunized with phycoerythrin 30 days prior. This Series includes the RNA-seq component of the study.
Publication Title
B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the role of EZH2 in Plasmablast function EZH2 was inducibly deleted using tamoxifen and B cells stimulated to differentiate with LPS in vivo. After 3 days, CD138+ cells were enriched from the spleens and RNA-seq was performed to identify the genes targeted by EZH2 for repression. Overall design: RNAseq on control or EZH2-deficient murine plasmablasts.
Publication Title
EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances and ER stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here we show that C/EBP:ATF4 heterodimers, but not C/EBP:ATF4 dimers, are the predominant CARE binding species in stressed cells. C/EBP and ATF4 associate with genomic CAREs in a mutually-dependent manner and co-regulate many ISR genes. By contrast, the C/EBP family members C/EBP and CHOP were largely dispensable for induction of stress genes. Cebpg/ MEFs proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg/ mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBP-deficient newborns die from atelectasis and respiratory failure which can be mitigated by in utero exposure to the anti-oxidant, N-acetyl-cysteine. Cebpg/ mice on a mixed strain background show improved viability but, upon aging, develop significantly fewer malignant solid tumors compared to WT animals. Our findings identify C/EBP as a novel anti-oxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells.
Publication Title
C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.
Sample Metadata Fields
Specimen part
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