Filters
Technology
Platform
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2500
Description
The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis. Overall design: mRNA expression levels are compared between IR-induced senescent and proliferating IMR90 cells in triplicate
Publication Title
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (Core OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.
Publication Title
The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple DNA methylation changes have been associated with the acquisition of drug resistance; however it remains uncertain how many of these changes may represent critical DNA methylation drivers of chemoresistance. Using gene expression profiling method on HGU133plus2 array, we identified a total of 1370 genes showing significant gene expression changes with 687 genes going up and 683 genes going down in the resistant (cp70) versus sensitive cell lines (A2780) by Rank Product (FDR<5%). Combining expression profiling with methylation profiling data we found out of 245 hypermethylated and down-regulated genes in the resistant cell line, 41 genes were up-regulated following Decitabine treatment alone, 45 genes up-regulated following combined treatment of Decitabine and PXD101, and only 10 genes up-regulated following PXD101 treatment alone. Altogether we found a small set of genes as being potential key drivers of chemoresistance and should be further evaluated as predictive biomarkers, both to existing chemotherapies, but also to epigenetic therapies used to modulate drug resistance.
Publication Title
Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Characterization of intraepithelial ILC on the basis of CD8 and Ly49E expression
Publication Title
A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell Population Characterized by Group 1 Properties.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Comparison between ex vivo immature, mature and stimulated T cells and in vitro generated counterparts. The T cells generated in vitro were cultured on OP9-DL1 stroma supplied with growth factors.
Publication Title
In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Illumina HiSeq 1500
Description
Floodings already have a nearly 60% share in the worldwide damage to crops provoked by natural disasters. Climate change will cause plants to be even more frequently exposed to oxygen limiting conditions (hypoxia) in the near future due to heavy precipitation and concomitant waterlogging or flooding events in large areas of the world. Although the homeostatic regulation of adaptive responses to low oxygen stress in plants is well described, it remained unknown by which initial trigger the molecular response to low-oxygen stress is activated. Here, we show that a hypoxia-induced decline of the ATP level of the cell reduces LONG-CHAIN ACYL-COA SYNTHETASE (LACS) activity, which leads to a shift in the composition of the acyl-CoA pool. High oleoyl-CoA levels release the transcription factor RELATED TO APETALA 2.12 (RAP2.12) from its interaction partner ACYL-COA BINDING PROTEIN (ACBP) at the plasma membrane to induce low oxygen-specific gene expression. We show that different acyl-CoAs provoke unique molecular responses revealing a novel role as cellular signalling component also in plants. In terms of hypoxia signalling, dynamic acyl-CoA levels integrate the cellular energy status into the oxygen signalling cascade with ACBP and RAP2.12 being the central hub. The conserved nature of the ACBP:RAP2.12 module in crops and the novel mechanistic understanding of how low-oxygen stress responses are initiated by oleoyl-CoA in plants provide useful leads for enhancing future food security. Overall design: 1 control and 3 treatments with different forms of acyl-CoA in triplicate biological replicates
Publication Title
Low-oxygen response is triggered by an ATP-dependent shift in oleoyl-CoA in <i>Arabidopsis</i>.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
GSE18497- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomewide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (stable group), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (skewed group), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication.
Publication Title
Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HiSeq 2500
Description
Background and Purpose—Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. Methods—We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. Results—We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. Conclusions—For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture. Overall design: RNA sequencing of 44 intracranial aneurysm samples (including 21 unruptured, 22 ruptured and 1 undetermined) and 16 control samples of the intracranial cortical artery
Publication Title
RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Colon cancer is a major cause of cancer deaths in Western countries and is associated with diets high in red meat. Heme, the iron-porphyrin pigment of red meat, induces cytotoxicity of gut contents which injures surface cells leading to compensatory hyperproliferation of crypt cells. This hyperproliferation results in epithelial hyperplasia which increases the risk of colon cancer. In humans, a high red-meat diet increases Bacteroides spp in feces. Therefore, we simultaneously investigated the effects of dietary heme on colonic microbiota and on the host mucosa of mice. Whole genome microarrays showed that heme injured the colonic surface epithelium and induced hyperproliferation by changing the surface to crypt signaling. Using 16S rRNA phylogenetic microarrays, we investigated whether bacteria play a role in this changed signaling. Heme increased Bacteroidetes and decreased Firmicutes in colonic contents. This shift was most likely caused by a selective susceptibility of Gram-positive bacteria to heme cytotoxic fecal water, which is not observed for Gram-negative bacteria, allowing expansion of the Gram-negative community. The increased amount of Gram-negative bacteria most probably increased LPS exposure to colonocytes, however, there is no appreciable immune response detected in the heme-fed mice. There was no functional change in the sensing of the bacteria by the mucosa, as changes in inflammation pathways and Toll- like receptor signaling were not detected. This unaltered host-microbe cross-talk indicates that the changes in microbiota did not play a causal role in the observed hyperproliferation and hyperplasia.
Publication Title
Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples