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SRP033220
Mus musculus
30 Downloadable Samples
Illumina HiSeq 2000
Description
Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. Here, we show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by inactivating the ROS-p53 axis. Because p53 inactivation occurs late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production. Overall design: There were 3 experimental groups (untreated, NAC-treated and Vitamin E-treated. Each group consisted of 5 animals, and from each animal we harvested 2 tumor samples. Hence, in total 3x10=30 samples were profiled.
Publication Title
Antioxidants accelerate lung cancer progression in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 9 Downloadable Samples
Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Orthopox viruses, including monkeypox, multiply intracellularly and induce numerous changes in host genes expression. The virus target mainly humoral host response, and simultaneously, exploits other genes and functions to reproduce effectively. The goal of this experiment is to identify those host genes and functions that are essential for monkeypox virus replication.
Publication Title
Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
Aged mdx mice were treated with 2.5x105 cardiosphere-derived cells (CDCs) or 2.0x109 exosomes intravenously. Hearts and skeletal muscles were harvested 3 weeks post-treatment and prepared for RNA sequencing. Overall design: Comparison of transcriptomic changes in mdx hearts and skeletal muscles by cardiac progenitor cell and exosome treatments
Publication Title
Disease-modifying bioactivity of intravenous cardiosphere-derived cells and exosomes in mdx mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Preterm birth is an important unsolved clinical problem. Despite advanced treatments, infants who survive prematurity remain at increased risk for permanent disabilities. In approximately one-third of cases, prematurity is related to infection and/or inflammation, which renders hostile the normally receptive intrauterine environment. Proinflammatory cytokines provoke up-regulation of genes that promote uterine contractions. Using monolayer cultures of human decidual cells as a model, we profiled the global pattern of gene expression in response to cytokine challenge.
Publication Title
Inflammatory gene networks in term human decidual cells define a potential signature for cytokine-mediated parturition.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer.
Publication Title
Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that core promoters are unidirectional and that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that about half of promoters are unidirectional and that these unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters. Overall design: Using 5''-GRO-seq and GRO-seq to determine mechanisms of divergent transcription initiation
Publication Title
Human promoters are intrinsically directional.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
DNA methylation is an essential epigenetic modification, present in both unique DNA sequences and repetitive elements, but its exact function in repetitive elements remains obscure. Here, we describe the genome-wide comparative analysis of the 5mC, 5hmC, 5fC and 5caC profiles of repetitive elements in mouse embryonic fibroblasts and mouse embryonic stem cells. We provide evidence for distinct and highly specific DNA methylation/oxidation patterns of the repetitive elements in both cell types, which mainly affect CA repeats and evolutionary conserved mouse-specific transposable elements including IAP-LTRs, SINEs B1m/B2m and L1Md-LINEs. DNA methylation controls the expression of these retro-elements, which are clustered at specific locations in the mouse genome. We show that TDG is implicated in the regulation of their unique DNA methylation/oxidation signatures and their dynamics. Our data suggest the existence of novel epigenetic code for the most recently acquired evolutionary conserved repeats that could play a major role in cell differentiation. Overall design: Transcriptome (RNA-seq) analyses of shRNA treated MEFs (control, shSCR or Tdg knockdown, shTDG).
Publication Title
Combinatorial DNA methylation codes at repetitive elements.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Microarray is widely used to monitor gene expression changes in breast cancer. The transcriptomic changes in breast cancer is commonly occured during the transition of normal cells to cancerous cells. This is the first study on gene expression profiling of multi ethnic of Malaysian breast cancer patients (Malays, Chinese and Indian). We aim to identify differentially expressed genes between tumors and normal tissues. We have identified a set of 33 significant differentially expressed genes in the tumor vs. normal group at p<0.001.
Publication Title
Gene expression patterns distinguish breast carcinomas from normal breast tissues: the Malaysian context.
Sample Metadata Fields
Specimen part, Disease stage, Race
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding Overall design: RNA-seq
Publication Title
Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 768 Downloadable Samples
- Illumina HiSeq 2500
Description
Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process. Overall design: Gene expression was characterized by single-cell RNA-seq during the direct programming of ES cells into motor neurons using over-expression of Ngn2-Isl1-Lhx3 programming factors.
Publication Title
A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples