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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- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
UMR106-01 osteoblastic cells are a model for studying bone mineralization. We have shown that mineralization is temporally synchronized within cultures grown under defined conditions . Cells are plated at time zero and differentiate into osteoblastic phenotype by 64 h later. If an exogenous phosphate source is added to the cultures, the cells form and deposit hydroxyapatite mineral within distinct extracellular supramolecular lipid protein complexes termed biomineralization foci (BMF) starting 12 h later. Mineralization is largely complete by 24 h later (88 h after plating). We have also shown that AEBSF, covalent serine protease inhibitor, blocks mineralization within BMF and inhibits the fragmentation of several proteins related to biomineralization. The present experiment was designed to test whether AEBSF treatment for 12 h has an effect on transcription by UMR106-01 osteoblastic cells. AEBSF is known to inactivate several serine proteases including SKI-1 (site 1, subtilisin kexin protease-1).SKI-1 functions intracellularly to activate transmembrane bound transcription factor precursors releasing the transcriptionally active N-terminal portions to imported into the nucleus. Thus, if AEBSF blocks transcription of mineralization related genes, it would support a role for SKI-1 in gene regulation in mineralizing UMR106-01 osteoblastic cells.
Publication Title
Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Use of expression data to analyse ovarian cancer often yields long lists of genes that do not agree across various studies. Copy number however is more stable and can reliable predict important regions of change. Using matched copy number and expressiion data helps accurately identify novel drivers of ovarian cancer.
Publication Title
Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.
Sample Metadata Fields
Age, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The objective of this experiment was to determine global gene expression change in triple negative cell line upon knockdown of TGFBR3. Genotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST affymetrix array. RNA was extracted from SUM159 controls and SUM159 TGFBR3KD cells cultured in 3-dimensional in vitro system.
Publication Title
Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer.
Sample Metadata Fields
Cell line
View Samples- Bos taurus
- 39 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Mycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host macrophages by subverting host immune responses via a diverse range of mechanisms. Here, a high-density bovine microarray platform was used to examine the bovine monocyte-derived macrophage transcriptome response to M. bovis infection relative to infection with the attenuated vaccine strain, M. bovis Bacille CalmetteGurin. Differentially expressed genes were identified (adjusted P-value 0.01) and interaction networks generated across an infection time course of 2, 6 and 24 h. The largest number of biological interactions was observed in the 24 h network, which exhibited small-worldscale-free network properties. The 24 h network featured a small number of key hub and bottleneck gene nodes, including IKBKE, MYC, NFKB1 and EGR1 that differentiated the macrophage response to virulent and attenuated M. bovis strains, possibly via the modulation of host cell death mechanisms. These hub and bottleneck genes represent possible targets for immunomodulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment.
Publication Title
Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 1500
Description
To define the molecular regulators of metastasis of triple-negative breast cancer, we conducted a rigorous characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that display a range of intrinsic spontaneous metastatic capacities in immuno-deficient mice, from non-metastatic to highly metastatic to lung, liver, spleen and spine. PAT-Seq gene expression profiling of primary tumor cells identified the fibroblast growth factor homologous factor, FGF13, as a candidate metastatic virulence gene highly upregulated in aggressively metastatic MDA-MB-231HM tumors. Overall design: Gene expression analysis from PAT-Seq of 4 increasingly metastatic breast cancer xenograft tumours
Publication Title
Functional and genomic characterisation of a xenograft model system for the study of metastasis in triple-negative breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Bos taurus
- 16 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Background: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix GeneChip Bovine Genome Array with features representing more than 23,000 gene transcripts and over 19,000 gene probe sets.
Publication Title
Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Purpose of arrays were to determine what the effect of deletion of Mbtps1 gene was on gene expression of osteocytes in bone in vivo. DMP1 cre driver was used to delete the Mbtps1 gene in osteocytes and osteoblasts in bone. We then isolated osteocyte enriched bone particles from 40 week old male mice to determine the effect of this deletion on gene expression. We have previously shown that Mbtps1 is needed for transcription of Phex, DMP1, and MEPE genes in osteoblasts in culture. Arrays showed these genes were reduced as expected in osteocytes in vivo. Controls represent osteocyte enriched bone from 40 week old littermates. Also, as expected, Mbtps1 expression was reduced in these knockout mice
Publication Title
Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age.
Sample Metadata Fields
Sex
View Samples- Bos taurus
- 77 Downloadable Samples
- Illumina HiSeq 2000
Description
Mycobacterium bovis, the agent of bovine tuberculosis, causes an estimated $3 billion annual losses to global agriculture due, in part, to the limitations of current diagnostics. Development of next-generation diagnostics requires a greater understanding of the interaction between the pathogen and the bovine host. Therefore, to explore the early response of the alveolar macrophage to infection, we report the first application of RNA-sequencing to define, in exquisite detail, the transcriptomes of M. bovis-infected and non-infected alveolar macrophages from ten calves at 2, 6, 24 and 48?hours post-infection. Differentially expressed sense genes were detected at these time points that revealed enrichment of innate immune signalling functions, and transcriptional suppression of host defence mechanisms (e.g., lysosome maturation). We also detected differentially expressed natural antisense transcripts, which may play a role in subverting innate immune mechanisms following infection. Furthermore, we report differential expression of novel bovine genes, some of which have immune-related functions based on orthology with human proteins. This is the first in-depth transcriptomics investigation of the alveolar macrophage response to the early stages of M. bovis infection and reveals complex patterns of gene expression and regulation that underlie the immunomodulatory mechanisms used by M. bovis to evade host defence mechanisms. Overall design: Whole-transcriptome analysis of M. bovis- and non-infected alveolar macrophages from ten calves (n = 10) at 2, 6, 24 and 48 hours (h) post-infection using RNA-sequencing (RNA-seq).
Publication Title
RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples