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SRP125196
Mus musculus
35 Downloadable Samples
Illumina HiSeq 2500
Description
This study analysed the transcriptome of mouse Rex1GFPd2 cells before and during early differentiation and further investigated the transcriptomic changes of Nprl2 and Tsc2 knockout. Overall design: RNA samples were collected before differentiation, and on day 1, 2, 3 of differentiation; RNA samples of Rex1GFP positive population were collected for Nprl2, Tsc2 knockout and compared to wild type cells.
Publication Title
Genome-wide CRISPR-KO Screen Uncovers mTORC1-Mediated Gsk3 Regulation in Naive Pluripotency Maintenance and Dissolution.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to compare the expression profiles between brains of BCAS1 knockout and wild type mice
Publication Title
Mice lacking BCAS1, a novel myelin-associated protein, display hypomyelination, schizophrenia-like abnormal behaviors, and upregulation of inflammatory genes in the brain.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
The major antioxidant glutathione (GSH) protects cancer cells from oxidative damage leading to ferroptosis, an iron-dependent cell death. Therapy-resistant cancer cells often manifest high expression of the cystine-glutamate antiporter subunit xCT which enhances cystine uptake leading to GSH synthesis and thereby survive oxidative damage and ferroptosis. The use of GSH-depleting agents including xCT inhibitors might thus be expected to enhance the efficacy of cancer therapy. On the other hand, the efficacy of xCT-targeted therapy depends on the cellular metabolism affecting antioxidant system in cancer cells and metabolic reprograming might reduce the efficacy of cancer therapy using xCT inhibitors. Recently, to overcome the resistance to xCT-targeted therapy, we performed a library screening and identified an oral anesthetics dyclonine (DYC) as a sensitizing drug for xCT inhibitor sulfasalazine (SSZ). However, DYC is a local anesthetic and might not suitable for the systemic administration combined with SSZ in a clinical setting. In this study, we identified a vasodilator oxyfedrine (OXY) which is clinically used in systemic administration also acts as a sensitizing drug to GSH-depleting agents in multiple type of cancer cells. OXY and DYC share the motif required for the covalent inhibition of aldehyde dehydrogenases (ALDHs), and combined treatment with OXY and SSZ induced the accumulation of cytotoxic aldehyde 4-hydroxynonenal (4-HNE) and induce cell death in SSZ-resistant cancer cells. Furthermore, we found that OXY sensitizes cancer cells to radiation therapy which decreases intracellular GSH content. Our findings establish a rationale for repurposing of OXY as a sensitizing drug for xCT-targeted cancer therapy.
Publication Title
Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 173 Downloadable Samples
- Illumina HiSeq 2500
Description
The synthetic cost of cycling genes is higher than other genes, and the cyclic expression pattern of these genes is a strategy for reducing the overall energy usage of cells Overall design: Samples for both conditions were taken over two metabolic cycles. For the fast cycling condition one sample was taken every 13 minutes for ~4.25 hours. For the slow cycling condition, samples were taken every 36 minutes for ~14.5 hours. Cycling genes were identified using JTK_Cycle (Hughes et al. (2010) Journal of Biological Rhythms).
Publication Title
Cycling Transcriptional Networks Optimize Energy Utilization on a Genome Scale.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 78 Downloadable Samples
- Illumina HiScanSQ
Description
The circadian clock in mammalian cells is cell-autonomously generated during the cellular differentiation process, but the underlying mechanisms are not understood. Here we show that perturbation of transcriptional program by constitutive expression of c-Myc and Dnmt1 ablation disrupts the differentiation-coupled emergence of the clock from mouse embryonic stem cells (ESCs). Using these model ESCs, 484 genes are identified by global gene expression analysis as correlating factors with differentiation-coupled circadian clock development. Among them, we find the misregulation of Kpna2 (Importin-alpha2) during the differentiation of the c-Myc over-expressed and Dnmt1-/- ESCs, in which sustaining cytoplasmic accumulation of PER proteins is observed. Moreover, constitutive expression of Kpna2 during the differentiation culture of ESCs significantly impairs clock development and KPNA2 facilitates cytoplasmic localization of PER1/2. These results suggest that the programmed gene expression network regulates the differentiation-coupled circadian clock development in mammalian cells, at least in part via post-transcriptional regulation of clock proteins. Overall design: Examination of whole transcriptome in ES cells and in vitro differentiated cells.
Publication Title
Transcriptional program of Kpna2/Importin-α2 regulates cellular differentiation-coupled circadian clock development in mammalian cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 72 Downloadable Samples
- Illumina HiSeq 2500
Description
Circadian clock oscillation emerges in mouse embryo in the later developmental stages. Although circadian clock development is closely correlated with cellular differentiation, the mechanisms of its emergence during mammalian development are not well understood. Here, we demonstrate an essential role of the post-transcriptional regulation of Clock subsequent to the cellular differentiation for the emergence of robust circadian clock oscillation in mouse fetal hearts and mESCs (mouse embryonic stem cells). In mouse fetal hearts, no apparent oscillation of cell-autonomous molecular clock was detectable in around embryonic day (E) 10 whereas robust oscillation was clearly visible in E18 heart. Temporal RNA-seq analysis using mouse fetal hearts reveals much fewer rhythmic genes in E10-12 hearts (63, no clock genes) than E17-19 (483 genes), indicating the lack of functional circadian clocks in E10 mouse fetal hearts. In both mESCs and E10 embryos, CLOCK protein was absent despite the expression of Clock mRNA, which we showed was at least partially due to miRNA-mediated translational suppression of CLOCK. The CLOCK protein is required for the robust molecular oscillation in differentiated cells, and the post-transcriptional regulation of Clock plays a key role in setting the timing for the emergence of the circadian clock oscillation during mammalian development.
Publication Title
Involvement of posttranscriptional regulation of <i>Clock</i> in the emergence of circadian clock oscillation during mouse development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
High fat diets are known to be a risk factor for prostate cancer. In this study, we investigated the effect of high fat diet on mouse prostate gene expression. C57BL/6J mice were fed either a control or high fat diet for 12 weeks. Microarray analyses were performed on mouse ventral prostate (VP) and dorsolateral prostate (DLP), followed by canonical pathway analysis and regulatory network identification. mRNA changes were confirmed by real time PCR. Approximately 2,125, and 1,194 genes responded significantly to the high fat diet in VP, DLP, respectively. Pathways and networks related to oxidative stress, glutathione metabolism, NRF-mediated oxidative stress response and NF-kappaB were all differentially regulated by high fat diet. GPx3 mRNA levels were decreased by approximately 2-fold by high fat diet in all 3 prostate lobes. In human non-transformed prostate cells (PrSC, PrEC and BPH-1), cholesterol loading decreased GPx3 expression, and increased H2O2 levels of culture medium. Troglitazone increased GPx3 expression in 3 normal prostate cells, and decreased H2O2 levels. In addition, troglitazone attenuated cholesterol-induced H2O2 increase. Tissue from prostate cancer biopsies had decreased GPx3 mRNA and its level was inversely related to the Gleason score.
Publication Title
High fat diet reduces the expression of glutathione peroxidase 3 in mouse prostate.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload evoked by FBXL5 ablation gives rise to oxidative stress, tissue damage, inflammation and compensatory proliferation in hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting effect of FBXL5 deficiency in the liver is also operative in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis induced by iron overload. Dysregulation of FBXL5-mediated cellular iron homeostasis was also found to be associated with poor prognosis in human HCC, implicating FBXL5 plays a significant role in defense against hepatocarcinogenesis. Overall design: Total RNA was extracted from the nontumor and tumor tissue of an Alb-Cre/Fbxl5F/F male mouse (nontumor, n = 5; tumor, n = 5) or two littermate control Fbxl5F/F mice (nontumor, n = 6; tumor, n = 6) at 45 weeks of age.
Publication Title
Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Under hypoxic conditions, nitroimidazole compounds accumulate in cells in their reduced form and have oxygen-mimetic effects, serving as markers of hypoxia and radiosensitizers. The full potential of their bioreductive metabolism, including cytotoxicity for cancer stem cells, has not been sufficiently explored, however. Here we investigated the changes in gene expression induced by treatment with 2-nitroimidazole doranidazole in murine glioma stem cells, under normoxic or hypoxic conditions.
Publication Title
2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype we performed DNA microarray analysis on white adipose tissue (WAT) from PeriA transgenic (Tg) and control wildtype (WT) mice.
Publication Title
Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype.
Sample Metadata Fields
Sex, Specimen part
View Samples