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Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Bone marrow mesenchymal stromal cells (MSCs) that express high levels of stem cell factor (SCF) and CXC chemokine ligand 12 (CXCL12) are one crucial component of the hematopoietic stem cell (HSC) niche. While the secreted factors produced by MSCs to support HSCs have been well described, little is known regarding the transcriptional regulators controlling the cell fate of MSCs and thus indirectly maintaining HSCs. Bmi1 is a polycomb group protein that regulates HSCs both cell intrinsically and extrinsically, but it is unknown in which cell type and how Bmi1 functions to maintain HSCs extrinsically. Here we show that Bmi1 maintains HSCs by preventing adipogenic differentiation of MSCs. Bmi1 is highly expressed in MSCs but becomes downregulated upon adipogenic differentiation and during aging. Deleting Bmi1 from MSCs increased marrow adipocytes, induced HSC quiescence and depletion, and impaired hematopoiesis. We found that Bmi1 repressed multiple developmental programs in MSCs by safeguarding the repressive epigenetic marks histone H2A ubiquitylation and H3 lysine 27 trimethylation. We identified a novel adipogenic program governed by Pax3, which Bmi1 repressed in MSCs. Our results establish Bmi1 as a critical regulator of MSC cell fate that suppresses marrow adipogenesis to create a supportive niche for HSCs. Overall design: RNA-Seq of two treatments (Ctrl, KO) with three replications per treatment.
Publication Title
Bmi1 Suppresses Adipogenesis in the Hematopoietic Stem Cell Niche.
Sample Metadata Fields
Specimen part, Subject
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- Sus scrofa
- 11 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how loss of CFTR first disrupts airway host defense has remained uncertain. We asked what abnormality impairs elimination when a bacterium lands on the pristine surface of a newborn CF airway? To investigate this defect, we interrogated the viability of individual bacteria immobilized on solid grids and placed on the airway surface. As a model we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly killed bacteria in vivo, when removed from the lung, and in primary epithelial cultures. Lack of CFTR reduced bacterial killing. We found that ASL pH was more acidic in CF, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defense defect to loss of CFTR, an anion channel that facilitates HCO3- transport. Without CFTR, airway epithelial HCO3- secretion is defective, ASL pH falls and inhibits antimicrobial function, and thereby impairs killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF and that assaying ASL pH or bacterial killing could report on the benefit of therapeutic interventions.
Publication Title
Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung.
Sample Metadata Fields
Specimen part
View Samples- Glycine max
- 2522 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
To identify soybean genes and QTLs associated with quantitative resistance to infection by the oomycete pathogen Phytophthora sojae, we conducted a very large-scale microarray experiment using 2522 Affymetrix GeneChips. The experiment involved assaying a total of 298 soybean recombinant inbred lines together with internal checks.
Publication Title
Infection and genotype remodel the entire soybean transcriptome.
Sample Metadata Fields
Specimen part
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- Homo sapiens
- 57 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Age-related variations in the methylome associated with gene expression in human monocytes and T cells.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 57 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The MESA Epigenomics and Transcriptomics Study has been launched to investigate potential gene expression regulatory methylation sites in humans by examining the association between CpG methylation and gene expression in purified human monocytes from a large study population (community-dwelling participants in the Multi-Ethnic Study of Atherosclerosis (MESA)).
Publication Title
Age-related variations in the methylome associated with gene expression in human monocytes and T cells.
Sample Metadata Fields
Age
View Samples
GSE34378- Mus musculus
- 90 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lifelong murine gene expression profiles in relation to chronological and biological aging in multiple organs
Publication Title
Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 191 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In MTN-007, a phase 1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies taken at baseline, after one application or after seven daily applications (15 subjects/arm). Experiments were repeated using primary vaginal epithelial cells from four healthy women.
Publication Title
Mucosal effects of tenofovir 1% gel.
Sample Metadata Fields
Specimen part, Treatment
View Samples