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GSE63830
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Although Hematopoietic Stem Cell Transplantation (HSCT) routinely treats hematologic disease, many patients experience adverse outcomes. Understanding the molecular regulation of HSC engraftment is paramount to improving HSCT regimens. Here, we executed a large-scale transplant-based functional screen for novel regulators of HSC repopulation.. Of >50 gene candidates tested, 18 were required for in vivo hematopoietic repopulation and two were detrimental to repopulation, as their loss enhanced this activity. Each Hit was validated in a second screen. Eleven Hits have never before been implicated in HSC biology. We further show that one novel Hit, Foxa3, is required for optimal engraftment as Foxa3-/- bone marrow is defective in both primary and secondary hematopoietic reconstitution. We also present evidence that Foxa3 is a novel pioneer factor in HSC. Each gene identified in our screen is a window into the cellular mechanisms that control hematopoietic reconstitution. Thus, this work represents a resource to the community to better understand these processes
Publication Title
Functional screen identifies regulators of murine hematopoietic stem cell repopulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Response of mouse mammary epithelial cells to treatment with MMP3
Publication Title
ROS-induced epithelial-mesenchymal transition in mammary epithelial cells is mediated by NF-kB-dependent activation of Snail.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus, Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Response of mouse mammary epithelial cells to different cell densities and treatment with MMP3
Publication Title
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Response of mammary epithelial cells to different cell densities
Publication Title
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The NF1 tumor suppressor encodes a RAS GTPase-Activating Protein (RasGAP). Accordingly, deregulated RAS signaling underlies the pathogenesis of NF1-mutant cancers. However, while various RAS effector pathways have been shown to function in these tumors, it is currently unclear which specific proteins within these broad signaling pathways represent optimal therapeutic targets. Here we identify mTORC1 as the key PI3K pathway component in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. We also report that combined mTORC1/MEK inhibition is required to promote tumor regression in animal models, but only when the inhibition of both pathways is sustained. Transcriptional profiling studies were also used to establish a predictive signature of effective mTORC1/MEK inhibition in vivo. Within this signature, we unexpectedly found that the glucose transporter gene, GLUT1, was potently suppressed but only when both pathways were effectively inhibited. Moreover, unlike VHL and LKB1 mutant cancers, reduction of 18F-FDG uptake measured by FDG-PET required the effective suppression of both mTORC1 and MEK. Together these studies identify optimal and sub-optimal therapeutic targets in NF1-mutant malignancies and define a non-invasive means of measuring combined mTORC1/MEK inhibition in vivo, which can be readily incorporated into clinical trials.
Publication Title
Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions. We previously demonstrated that adenosine 5'-triphosphate (ATP) inhibits the proliferation while stimulating the migration, in vitro and in vivo, of human bone marrow-derived mesenchymal stem cells (BM-hMSC). Here, we investigated the effects of ATP on BM-hMSC differentiation capacity.
Publication Title
Extracellular purines promote the differentiation of human bone marrow-derived mesenchymal stem cells to the osteogenic and adipogenic lineages.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CBP, a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Morphological and behavioral analyses demonstrated that EE ameliorates deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-enhanced spatial navigation and patter separation ability. These defects correlated with an attenuation of the transcriptional program induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics.
Publication Title
CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 78 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: We investigated the tetrachloroethylene associated changes in kidney transcriptomes among healthy mice, nonalcoholic fatty liver disease mice, and nonalcoholic steatohepatitis mice. Overall design: Male C57BL/6J mice were fed a low-fat diet (4% fat), high-fat diet (31% fat), or methionine/choline/folate deficient diet. Following an 8-week diet, mice were administered either a single dose of tetrachloroethylene (PERC, 300 mg/kg/d in 5% Alkamuls-EL620 in saline, 5 mL/kg) and euthanized at 24 hours post dose, or five consecutive daily doses of PERC or vehicle (n=8/diet/treatment) and euthanized at 4hours post dose. The harvested kidneys were subjected to mRNA sequencing using Illumina Hiseq 2500. Jac-NASH-063 was excluded from analysis because it did not have a good yield.
Publication Title
Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples