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Homo sapiens
27 Downloadable Samples
Illumina HiSeq 4000
Description
CD19-specific CARs that comprise CD28 and CD3z signaling domains program highly performing effector functions that mediate potent tumor elimination, but they impart a relatively limited T cell lifespan. Increasing functional T cell persistence without reducing effector potency is therefore likely to further enhance the therapeutic success of 1928z CAR T cells. We demonstrate that the number and position of ITAMs in 1928z CAR T cells influence functional, phenotypic and transcriptional programs, resulting in profound effects on antitumor efficacy. Improved therapeutic potency of CAR T cells can thus be achieved by calibrating activation strength, thereby retaining memory functions and preventing exhaustion, without compromising effector functions. Our transcriptional analysis underscores the potential of ITAM dosage and position to direct different T cell fates. We were able to identify a novel CAR design, termed 1XX, which programs a favorable balance of effector and memory signatures, inducing increased persistence of highly functional CARs with the replicative capacity of long-lived memory cells and potent effector functions. Overall design: In order to assess the different phenotypic and functional patterns of CARs encoding a single immunoreceptor tyrosine-based activation motif (ITAM), we compared the genome-wide transcriptional profiles of 1928z, 1XX and XX3 after CD19 antigen stimulation of TRAC-edited naïve T cells. Sorted naïve (TN), stem cell memory (TSCM) and effector (TEFF) CD8+ T cells served as controls.
Publication Title
Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency.
Sample Metadata Fields
Specimen part, Subject
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SRP044651- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
We generate ZNF423 knockdown and control DAOY cells with lentivirus that co-expressed the fluorescent protein mCherry. We performed whole genome RNA sequencing (RNA-seq) of three batched of cultured ZNF423 KD or control KD cells. The sequence reads were analyzed by Homer followed by edgeR. The analyzed RNA-seq results showed differential expression profile including 12 known cilia genes, and 3 of these were validated with qRT-PCR on mouse granule cell precursors. This study proved data how ZNF423 linked to cilia complexes. Overall design: RNA-seq in three batched of control and ZNF423 KD cells(generated by lentivirus delivered shRNA targeting ZNF423 sequence).
Publication Title
Zfp423 Regulates Sonic Hedgehog Signaling via Primary Cilium Function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 59 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone.
Publication Title
Laboratory diet profoundly alters gene expression and confounds genomic analysis in mouse liver and lung.
Sample Metadata Fields
No sample metadata fields
View Samples GSE11056- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone.
Publication Title
Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
To investigate the relationship between histones, chaperone function, and cataracts, we performed RNA-seq, isothermal titration calorimetry (ITC), size-exclusion chromatography, and gel electrophoresis of histones. The RNA-seq of postnatal lenses from 2-day-old cryaa -R49C mice revealed increased histone gene expression, suggesting that a a-crystallin mutation regulates histones via a transcriptional mechanism . Overall design: RNA-seq studies on lenses of 2-day-old wild-type and 2-day-old cryaa-R49C heterozygous mutant and cryaa-R49C homozygous mutant knock-in mice; and 14-day old wild-type and 14-day-old cryab-R120G heterozygous mutant and cryab-R120G homozygous mutant knock-in mice
Publication Title
Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Introduction: Mechanisms that contribute to the pathogenesis of liver damage caused by hepatitis C virus (HCV) are not fully understood. Our previous work on liver biopsies from chronic HCV patients has shown modulation of the expression of certain cell cycle proteins indicating HCV-induced modifications of cell cycle events. We therefore hypothesize that HCV infection disrupts normal regulation of cell cycle that contributes to disease progression. Objective: To identify molecular disruptions during the course of HCV-associated disease progression, using liver biopsy specimens of chronic hepatitis C patients. Methods: Liver biopsy samples classified on histological basis as early (fibrosis stage 0-1) or advanced (fibrosis stage 3-4) disease stage were studied using oligonucleotide array ( HG U133 Plus 2.0, Affymetrix GeneChip System). For comparison, liver specimens from patients with non-viral hepatitis were also analyzed by microarray. Expression data was analyzed using Genespring (GX 7.2) and Ingenuity Pathway analysis (3.0). The differential expression of selected cell cycle genes (cyclin D2, KPNA2, HERC5 and Bcl-2) identified after microarray analysis was confirmed by quantitative real-time RT-PCR. Results: Microarray analysis revealed two-fold or greater transcriptional change in 792 genes of the total 38,500 known human genes in HCV-advance disease stage (HCV-A) as compared to HCV-early disease stage (HCV-E). Most of the genes have a defined role in immune response, extracellular matrix and cell cycle and apoptosis.
Publication Title
Gene profiling of early and advanced liver disease in chronic hepatitis C patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression of periphereal blood lymphocytes (PBLs) of patients with metastatic renal cell carcinoma pre and post immunotherapy was accessed and pre therapy gene expression was compared to PBL gene expression of healthy volunteers
Publication Title
Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER) is highly expressed in ovarian granulosa cells and mice lacking ER (ERKO) are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions. Herein, we isolated preovulatory granulosa cells from WT and ER-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ER-null ovaries. ER-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ER in granulosa cells. LH responsive genes including Abcb1b and Fam110c show reduced expression in ER-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggests that granulosa cells from ER-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation
Publication Title
The absence of ER-β results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The p53 tumor suppressor is a DNA damage responsive sequence-specific transcriptional activator. The sustained activation of the p53 response is incompatible with cell growth and viability. To circumvent this issue, a variety of negative feedback loops exist to limit the duration of p53 activation. Despite our understanding of p53-regulation, very little is known about the effect of transient p53 activation on the long term expression of p53 target genes. Here we used a temperature sensitive variant of p53 and oligonucleotide microarrays to monitor gene expression during and following reversible p53 activation. The expression of most p53-induced transcripts was rapidly reversible, consistent with active mRNA decay. Representative 3UTRs derived from short-lived transcripts (i.e. DDB2 and GDF15) conferred instability on a heterologous mRNA while 3UTRs derived from more stable transcripts (i.e. CRYAB and TP53I3) did not. The 3UTRs derived from unstable p53-induced mRNAs were significantly longer than those derived from stable mRNAs. These 3UTRs had high uridine and low cytosine content, leading to a higher density of U-, AU- and GU-rich sequences. Remarkably, short-lived p53 targets were induced faster reaching maximum transcript levels earlier than the stable p53-targets. Taken together, the p53 transcriptional response has evolved with primarily short-lived target mRNAs and that post-transcription processes play a prominent role in the p53 response.
Publication Title
The role of mRNA decay in p53-induced gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2500
Description
Mononuclear phagocytes are a diverse cell family that occupy all tissues and assume numerous functions to support tissue and systemic homeostasis. Our ability to investigate the roles of individual subsets is limited by an absence of approaches to ablate gene function within specific sub-populations. Using Nr4a1-dependent Ly6Clow monocytes as a representative cell type we show that enhancer deletion addresses these limitations. Combining ChIP-Seq and molecular approaches we identify a single, conserved, sub-domain within the Nr4a1 enhancer that is essential for Ly6Clow monocyte development. Mice lacking this enhancer lack Ly6Clow monocytes but retain Nr4a1 gene expression in macrophages during steady state and in response to LPS. Nr4a1 is a key negative regulator of inflammatory gene expression and decoupling these processes allows Ly6Clow monocytes to be studied without confounding influences. Enhancer targeting possesses greater specificity than cre recombinase-mediated gene deletion, providing a route to generate loss-of-function models in closely related cell types. Overall design: Paired End mRNA sequencing of FACS purified primary murine MDP, cMoP, Ly6Chi and Ly6Clow monocytes from the bone marrow and Ly6Chi and Ly6Clow monocytes from the peripheral blood
Publication Title
Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6C<sup>low</sup> Monocytes while Preserving Macrophage Gene Function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples