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SRP136021
Mus musculus
384 Downloadable Samples
Illumina HiSeq 2500
Description
Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells including mesenchymal stem cells, macrophages and fibrocytes to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium we confirm that proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney fibrosis, we demonstrate that a small fraction of genetically labeled renal myofibroblasts derive from the circulation. Single cell RNA-Sequencing confirms this finding but indicates that these cells are circulating monocytes, express few extracellular matrix or other myofibroblast genes and do express many proinflammatory cytokines. We conclude that this small circulating myofibroblast progenitor population contributes to renal fibrosis by paracrine rather than direct mechanisms. Overall design: Single cell RNA-seq was performed on FACS-sorted PDGFRB+CD45- and PDGFRB+CD45+ cell populations
Publication Title
Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis.
Sample Metadata Fields
Age, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Deregulation of cytokine- and growth factor signaling due to altered expression of endogenous regulators is well recognized in prostate and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of growth hormone, IGF and prolactin signaling, that have been implicated in carcinogenesis. In this study we elucidate expression pattern and functional significance of SOCS2 in prostate cancer (PCa). Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed significantly enhanced expression in tumor compared to benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited prostate cancer cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we prove for the first time that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with androgen receptor expression in malignant tissue of patients. Taken together, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo.
Publication Title
SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
Sample Metadata Fields
Treatment, Time
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Rat small intestine precision cut slices were exposed for 6 hours to in vitro digested yellow (YOd) and white onion extracts (WOd) that was followed by transcriptomics analysis. The digestion was performed to mimic the digestion that in vivo takes place in the stomach and small intestine. The transcriptomics response of the rat small intestine precision cut slices was compared to that of human Caco-2 cells and the pig in-situ small intestinal segment perfusion. The microarray data for the human Caco-2 cells (GSE83893) and the pig in-situ small intestinal segment perfusion (GSE83908) have been submitted separately from the current data on rat intestine. The goal was to obtain more insight into to which extent mode of actions depend on the experimental model. A main outcome was that each of the three models pointed to the same mode of action: induction of oxidative stress and particularly the Keap1-Nrf2 pathway.
Publication Title
Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, in this study we explored the applicability of an in vitro model, namely human intestinal Caco-2 cells, to study the effect of food compounds on (intestinal) health. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into their mode of actions in the intestinal cells. Methods: Caco-2 cells were incubated with in vitro digested onion extracts for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. To identify onion-induced gene expression profiles in Caco-2 cells, digested yellow onion and white onion samples were compared to a digest control samples. Results: We found that yellow onion (n=5586, p<0.05) had a more pronounced effect on gene expression than white onion (n=3688, p<0.05). However, a substantial number of genes (n=3281, p<0.05) were affected by both onion variants in the same direction. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Conclusion: our data indicate that the in vitro Caco-2 intestinal model can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.
Publication Title
Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6 9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The diff erence between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25 + CD4 + regulatory T cells since their depletion did not abrogate the therapeutic eff ect of ICOSL blockade. Microarray analysis revealed IFN- and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction.
Publication Title
Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury. Overall design: Lung mRNA profiles of 3 months-old Igf1rfl/fl normal/control transgenic mice were generated by deep sequencing using Illumina GAIIx. ------------------------------------------- Submitter states "we use data on the absolute transcription levels (FPKM) of same IGF system genes on the adult "normal" mouse lung to compare them with those reported in the human adult lung (expressed in both as FPKM) (http://www.proteinatlas.org/)".
Publication Title
Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role during Repair Kinetics after Selective Club Cell Ablation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Sulphur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulphur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulphate starvation have been studied in the past, knowledge of the regulation of sulphur metabolism is still fragmentary. This work focuses on the discovery of candidates for regulatory genes such as transcription factors (TFs) using omics technologies. For this purpose a short term sulphate-starvation / re-supply approach was used. ATH1 microarray studies and metabolite determinations yielded 21 TFs which responded more than 2-fold at the transcriptional level to sulphate starvation. Categorization by response behaviors under sulphate-starvation / re-supply and other nutrient starvations such as nitrate and phosphate allowed determination of whether the TF genes are specific for or common between distinct mineral nutrient depletions. Extending this co-behavior analysis to the whole transcriptome data set enabled prediction of putative downstream genes. Additionally, combinations of transcriptome and metabolome data allowed identification of relationships between TFs and downstream responses, namely, expression changes in biosynthetic genes and subsequent metabolic responses. Effect chains on glucosinolate and polyamine biosynthesis are discussed in detail. The knowledge gained from this study provides a blueprint for an integrated analysis of transcriptomics and metabolomics and application for the identification of uncharacterized genes.
Publication Title
Transcriptome and metabolome analysis of plant sulfate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulfur, nitrogen and phosphorus nutritional responses in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 6 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
To identify genes that are regulated by SERF1, we performed expression profiling on roots of serf1 and wild-type plants under standard growth conditions.
Publication Title
SALT-RESPONSIVE ERF1 is a negative regulator of grain filling and gibberellin-mediated seedling establishment in rice.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used Arabidopsis full-genome microarrays to characterize plant transcript accumulations in map65-3 and ugt76b1 mutants, 3 days after water treatment and inoculation with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis (Hpa)
Publication Title
The Arabidopsis microtubule-associated protein MAP65-3 supports infection by filamentous biotrophic pathogens by down-regulating salicylic acid-dependent defenses.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis, like varying dormancy periods of Mets originating from the same primary tumor entity or the differing number of Mets in patients with the same primary tumor, are largely unknown. Knowing the molecular fundamentals of these phenomena would support the prognosis of patients outcome and facilitate the decision for an appropriate therapy regime.
Publication Title
Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient.
Sample Metadata Fields
Sex
View Samples