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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- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation
Publication Title
Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD25, the high affinity interleukin-2 (IL-2) receptor alpha-chain, is rapidly upregulated by antigen-specific CD8+ T cells after T cell receptor stimulation. We demonstrated that during an acute viral infection, CD25 expression was dynamic, and a subset of virus-specific CD8+ T cells sustained CD25 expression longer than the rest. Examination of the in vivo fate of effector CD8+ T cells exhibiting differential responsiveness to IL-2 revealed that CD25lo cells, which were relatively less sensitive to IL-2, preferentially upregulated CD127 and CD62L and gave rise to the functional long-lived memory pool. In contrast, CD25hi cells that accumulate enhanced IL-2 signals, proliferated more rapidly, were prone to apoptosis, exhibited a more pronounced effector phenotype, and appeared to be terminally differentiated. Sustained IL-2 receptor signaling resulted in increased CD8+ T cell proliferation, higher granzyme B expression and exaggerated contraction after antigen clearance. These data support the hypothesis that prolonged IL-2 signals during priming promote terminal effector differentiation of CD8+ T cells.
Publication Title
Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Tfh and B cells were cultured together with or without Tfr cells. After 4 days Tfh and B cells were sorted and prepared for 3'' targeted RNA-seq. Overall design: Examination of transcriptional changes upon suppression of Tfh and B cells.
Publication Title
Suppression by T<sub>FR</sub> cells leads to durable and selective inhibition of B cell effector function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Tfh and B cells were cultured together with or without Tfr cells and IL-21. After 4 days Tfh and B cells were sorted and prepared for 3'' targeted RNA-seq. Overall design: Examination of transcriptional changes upon IL-21 rescue of B cell suppression
Publication Title
Suppression by T<sub>FR</sub> cells leads to durable and selective inhibition of B cell effector function.
Sample Metadata Fields
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