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GSE135858
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- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We discover drugs with a dual-inhibitory mechanism provides a unique pharmacological strategy against cancer and evidence of cross-activation between the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways via a RasPIK3IP1PI3K signaling network
Publication Title
Dual blockade of the lipid kinase PIP4Ks and mitotic pathways leads to cancer-selective lethality.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
U87MG is a glioblastoma cell line that shows substantial heterogeneity despite long-term passaging.
Publication Title
Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regeneration of skeletal muscle is dependent on the function of tissue-resident muscle stem cells (MuSC), known as satellite cells. MuSC dysfunction is central to muscle pathophysiology, including in age-associated loss of muscle regenerative capacity and congenital disorders such as Duchenne muscular dystrophy. Despite the central role of satellite cells in muscle regeneration, the signals controlling the balance between muscle stem cell quiescence, proliferation, and differentiation remain incompletely understood. Knowledge of the signals that maintain a quiescent state is particularly lacking, yet such cues are crucial to maintaining a stem cell reservoir that can meet the needs of regeneration throughout life. Here we identify Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent and essential trans-acting regulator of satellite cell quiescence. Key to this discovery is the development of a novel in vivo imaging-based screening strategy allowing identification of proteins that do not induce in vitro proliferation, but instead maintain MuSCs in a non-mitotic state, poised for rapid robust expansion upon transplantation. We demonstrate that OSM induces reversible exit from the cell cycle and induction of a global transcriptional program significantly enriched within a newly established satellite cell quiescence signature. Genetic ablation of the OSM receptor in mice demonstrates that signaling via OSM/R is essential for maintenance of satellite cell quiescence, and for proper skeletal muscle regeneration in vivo. Given that aberrant activation and exhaustion of stem cells is seen in a variety of disorders, OSM constitutes an attractive therapeutic target in muscle disease states.
Publication Title
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response.
Publication Title
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The majority of sporadic colorectal cancer cases are initiated by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Several pre-clinical models carrying germline mutations in the endogenous mouse Apc tumor supressor gene have been generated and their phenotype characterized. The predisposition of these mouse models to multiple intestinal adenomas closely resembles the FAP phenotype at the molecular, cellular and phenotypic level and may prove valuable to elucidate the molecular and cellular mechanisms underlying colorectal tumorigenesis. The goal of this study is to establish an expression signature characteristic of intestinal tumors characterized by the inactivation of Apc.
Publication Title
Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Understanding the molecular underpinnings of cancer is of critical importance to developing targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multi-faceted cellular phenotype thus only have been identified following signaling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signaling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state. Remarkably, 14 among 24 such 'cooperation response genes' (CRGs) were found to contribute to tumor formation in gene perturbation experiments. In contrast, only one in 14 perturbations of genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain and loss-of-function mutations.
Publication Title
Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
In this study we plan to compare the profiles of control sample (cultured podocytes) with the Exoc5 knock down in cutured podocytes to examine the differentially expressed genes. Overall design: We hope to identify the genes that are downregulated on knocking down Exoc5 in cultured human podocytes cells
Publication Title
Disruption of the exocyst induces podocyte loss and dysfunction.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Characterize functional alterations in stem cells and paneth cells obtained from young and aged mice, focusing on age-based impairment of intestinal regeneration due to a decline in canonical Wnt signaling. Methods: mRNA profiles of young and aged stem and paneth cells were generated in triplicate (with one additional young paneth sample) using the Illumina HiSeq 2500. Reads that passed quality filters were aligned to the mm10 mouse genome with annotations provided by UCSC. Results: Approximately 10 millions reads were aligned per sample, corresponding to 36186 transcripts -- of these, 19574 exhibited reasonable expression. The effect of age was tested wtihin paneth and stem cells, using unpaired t-tests with a p-value cutoff of 0.05 and fold change cutoff of 1.5. Within paneth cells, 1025 genes were significant; within stem cells, 750 genes exhibited differential regulation. Among the downregulated genes in paneth and stem cells, we observed significant enrichment of canonical Wnt signaling genes. Conclusion: Age-related downregulation of canonical Wnt signaling is involved in the impairment of intestinal regulation upon aging. Overall design: mRNA profiles of paneth and stem cells obtained from proximal intestinal crypts from aged and young male Lgr5 mice were generated using RNAsequencing in triplicate, using Illumina HiSeq 2500.
Publication Title
Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples