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SRP052998
Homo sapiens
20 Downloadable Samples
IlluminaHiSeq2500
Description
Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J? in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control. Overall design: Human Dermal Fibroblasts were transfected with two different siRNA against CSL in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis.
Publication Title
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J-kappa in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, with p53 activation providing a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblasts senescence, enhances CAF effector gene expression and, in vivo, promotes stromal and cancer cell expansion. Together, these findings support a CAF activation/stromal evolution model under convergent CSL/p53 control.
Publication Title
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of differential gene expression. The influence of a constitutively activated mutant Kit receptor on gene expression in fetal hematopoietic cells was analyzed. Results provide information of genes and cellular processes that are influenced by Kit signaling.
Publication Title
Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Huntingtons disease (HD) is a neurodegenerative disorder that is associated with the deposition of proteinaceous aggregates in the brains of HD patients and mouse models. Previous studies have suggested that wide-scale disruption of protein homeostasis occurs in protein folding diseases. Protein homeostasis can be maintained by activation of the heat shock response (HSR) via the transcription factor heat shock factor 1 (HSF1), the pharmacological activation of which can be achieved by Hsp90 inhibition and has been demonstrated to be beneficial in cell and invertebrate models of HD. Whether the HSR is functional in HD and whether its activation has therapeutic potential in mammalian HD models is currently unknown. To address these issues, we used a novel, brain penetrant Hsp90 inhibitor to activate the HSR in brain after systemic administration. Microarrays, quantitative PCR and western blotting showed that the HSR becomes impaired with disease progression in two mouse models of HD and that this originates at the level of transcription.
Publication Title
Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
In rodents, the uterus of a mature
Publication Title
Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
17-Estradiol (E2) is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway.
Publication Title
Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Under various pathophysiological muscle-wasting conditions like diabetes and starvation, a family of ubiquitin ligases, including MuRF1 (Muscle specific RING-Finger protein 1), are induced to target muscle proteins for degradation via ubiquitination. In an attempt to identify the in vivo targets of MuRF1 we have generated transgenic mouse lines overexpressing MuRF1 in a skeletal muscle specific fashion. MuRF1-TG lines were viable and had normal fertility. Characterization of their skeletal muscles did not reveal evidence for muscle wasting at 10 weeks of age. In this experiment we compared the skeletal muscle transcriptome of transgenic mice with wildtypes.
Publication Title
MuRF1-dependent regulation of systemic carbohydrate metabolism as revealed from transgenic mouse studies.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- NextSeq 500
Description
We report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait. Overall design: Examination of the expression profile of mice adipose tissues fed either standard (Std), High-fat/high-sucrose (HF/HS) or HF/HS + antioxidant formulation (AOF) for 180 days
Publication Title
Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Populus trichocarpa
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Illumina HiSeq2000 technology was used to generate mRNA profiles from the ectomycorrhizal fungi Laccaria bicolor colonizing roots of Populus trichocarpa. Samples were taken after 3 months of contact in order to identify mycorrhiza-regulated transcripts. 100bp reads were generated and aligned to the Populus trichocarpa (http://www.phytozome.net/poplar.php) reference genome. Overall design: mRNA profiles from Populus trichocarpa roots colonized by Laccaria bicolor for three months as well as from control roots were generated by using one lane of 1X100bp Illumina HiSeq2000 sequencing per sample.
Publication Title
Populus trichocarpa encodes small, effector-like secreted proteins that are highly induced during mutualistic symbiosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The response of bacteria to the conditions at the site of infection is a key part of the transcriptional program that will determine the sucess of the infectious agent. To model the environment of the distal airway, we used bovine pulmonary surfactant (Survanta). P. aeruginosa transcript levels were measured in the presence or absence of Survanta in MOPS minimal medium to identify transcripts altered in response to surfactant. The most highly induced transcript in Survanta was PA5325, renamed sphA based on our findings that the gene was specifically induced by sphingosine derived from the sphingomyelin present in pulmonary surfactant. A divergently transcribed transcription factor, PA5324, was demonstrated to be critical for the sphingosine dependent induction of sphA and was therefore renamed SphR. Microarrays of the sphR mutant cells were compared to wild type to determine the likely SphR regulon.
Publication Title
Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
Sample Metadata Fields
Treatment
View Samples