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GSE57141
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- Mus musculus
- 23 Downloadable Samples
NextSeq 500
Description
Mammalian epidermal stem cells maintain homeostasis of skin epidermis and contribute to its regeneration throughout adult life. While two-dimensional mouse epidermal stem cell cultures have been established decades ago, a long-term, feeder cell- and serum-free culture system recapitulating murine epidermal architecture has not been available. Here we describe an epidermal organoid culture system that allows long-term, genetically stable expansion of adult epidermal stem cells. Our epidermal expansion media combines atypically high calcium concentrations, activation of cyclic AMP, FGF and R-spondin signaling with inhibition of BMP signaling. Organoids are established robustly from adult mouse skin and expand over at least 6 months, while maintaining the basal-apical organization of the mouse interfollicular epidermis. The system represents a powerful tool to study epidermal homeostasis and disease in vitro. Overall design: We establish an organoid culture system for long-term expansion of mouse epidermal stem cells. Using histological methods as well as low-coverage multiplexed RNA sequencing, we show that cultured organoids resembled interfollicular epidermis. We analyzed a total of 23 samples, including 6 controls that are isolated from the skin of mice. None-passaged as well as cultured organoids were compared with replicates. Differences growth factors and small molecules that allow expansion of organoids were compared with replicates.
Publication Title
Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures.
Sample Metadata Fields
Cell line, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Sulfite reductase (SiR) plays an essential role in the assimilatory sulfur reduction pathway by catalyzing the reduction of sulfite to sulfide. The T-DNA insertion mutant line sir1-1 shows lower amounts of SiR transcript, protein and lower activity and is severely affected in growth. In this study we performed global transcriptome analysis to investigate the impact of the mutation in the shoot of 7-week-old plants.
Publication Title
Sulfur availability regulates plant growth via glucose-TOR signaling.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Persons with Down syndrome (DS) exhibit low muscle strength that significantly impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits muscle weakness in vivo and may serve as a useful model to examine potential factors responsible for DS-associated muscle dysfunction. Therefore, the purpose of this experiment was to directly assess skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms of DS-associated muscle weakness. Soleus muscles were harvested from anesthetized male Ts65Dn and wild-type (WT) colony controls. In vitro muscle contractile experiments revealed normal force generation of unfatigued Ts65Dn soleus, but a 12% reduction in force was observed in Ts65Dn muscle during recovery following fatiguing contractions compared to WT muscle (p<0.05). Oxidative stress may contribute to DS-related pathologies, including muscle weakness, which may be the result of overexpression of chromosome 21 genes (e.g., copper-zinc superoxide dismutase (SOD1)). SOD1 expression was 25% higher (p<0.05) in Ts65Dn soleus compared to WT muscle but levels of other antioxidant proteins were unchanged. Lipid peroxidation (4-hydroxynoneal) was unaltered in Ts65Dn muscle although protein carbonyls were 20% greater compared to muscle of WT animals (p<0.05). Cytochrome c oxidase expression was reduced 22% in Ts65Dn muscle, suggesting a limitation in mitochondrial function may contribute to post-fatigue muscle weakness. Microarray analysis of Ts65Dn soleus revealed alteration of numerous cellular pathways including: proteolysis, glucose and fat metabolism, neuromuscular transmission, and ATP biosynthesis. In summary, the Ts65Dn mouse displays evidence of muscle dysfunction, and the potential role of mitochondria and oxidative stress warrants further investigation.
Publication Title
Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- NextSeq 500
Description
Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated single cell transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Publication Title
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- NextSeq 500
Description
Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Publication Title
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has been implicated in the pathogenesis and/or severity of several lung diseases, including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar macrophages are the main resident leukocytes exposed to inhaled antigens. Objectives: To obtain insight into which innate immune pathways become activated within human alveolar macrophages upon exposure to LPS in vivo.
Publication Title
Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in humans.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Data defines for the first time a whole bladder transcriptome of UPEC cystitis in female C57BL/6 mice using genome-wide expression profiling to map early host response pathways stemming from UPEC colonization
Publication Title
Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Data defines for the first time a whole bladder transcriptome of UPEC cystitis in female CBA mice using genome-wide expression profiling to map early host response pathways stemming from UPEC colonization
Publication Title
Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Butyrate induces Treg via HDACi activity
Publication Title
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Sample Metadata Fields
Specimen part, Treatment
View Samples