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GSE53077
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying (TA) matrix cells. EPs can revert to SCs upon injury, but whether this de-differentiation occurs in normal HF homeostasis (hair cycle), and the mechanisms regulating both differentiation and de-differentiation are unclear. Here we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression implements hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome towards a cell-state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and de-differentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.
Publication Title
High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. Overall design: DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.
Publication Title
The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.
Publication Title
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Phloem-feeding pests cause extensive crop damage throughout the world yet little is understood about how plants perceive and defend themselves from these threats. The silverleaf whitefly (SLWF; Bemisia tabaci type B) is a good model for studying phloem-feeding insect-plant interactions as SLWF nymphs cause little wounding and have a long, continuous interaction with the plant. Using the Arabidopsis ATH1 GeneChip, the global responses to Silverleaf Whitefly 2nd instar feeding were examined.
Publication Title
Arabidopsis transcriptome changes in response to phloem-feeding silverleaf whitefly nymphs. Similarities and distinctions in responses to aphids.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Staphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention. Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection. Overall design: mRNA expression analysis. 16 samples are from 2 donors, 8 samples per donor, 2 time points (4hr and 16 hr), and 4 conditions (control, TSLP treated, Heat Killed MRSA treated, and TSLP+HKM treated) .
Publication Title
A TSLP-complement axis mediates neutrophil killing of methicillin-resistant <i>Staphylococcus aureus</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To identify genes important in fetal preparation for birth.
Publication Title
Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in mammalian intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 151 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Three different cell populations (6 healthy B-lymphocytes, 6 leukemic CLL B-lymphocyte of indolent form and 5 leukemic CLL B-lymphocyte of aggressive form) were stimulated in vitro with an anti-IgM antibody, activating the B-cell receptor (BCR). We analyzed the gene expression at 4 time points (60, 90, 210 and 390 minutes). Each gene expression measurement is performed both in stimulated cells and in control unstimulated cells.
Publication Title
Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and 4 including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Publication Title
Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.
Sample Metadata Fields
Age
View Samples- Bos taurus
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
Our hypothesis was that genes differentially expressed in the endometrium and corpus luteum on day 13 of the estrous cycle between cows with either good or poor genetic merit for fertility would be enriched for genetic variants associated with fertility. We combined a unique genetic model of fertility (cattle which have been selected for high and low fertility and show substantial difference in fertility), with gene expression data from these cattle, and genome-wide association study (GWAS) results in ~20,000 cattle, to identify quantitative trait loci (QTL) regions and sequence variants associated with genetic variation in fertility. Overall design: 26 samples total; 8 Fert+ (high fertility) endometrium, 6 Fert- (low fertility) endometrium; 7 Fert+ corpus luteum, 5 Fert- corpus luteum; Fert+ Fert- differential gene expression analysis
Publication Title
Differentially Expressed Genes in Endometrium and Corpus Luteum of Holstein Cows Selected for High and Low Fertility Are Enriched for Sequence Variants Associated with Fertility.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study we investigate the mechanism of drug addiction Overall design: Drug was withdrawn from wt / MAPK1 KO / JUNB KO double drug resistant mel888 (DR Mel888) cells, and gene expression profiling was performed upon drug withdrawal
Publication Title
Cancer drug addiction is relayed by an ERK2-dependent phenotype switch.
Sample Metadata Fields
Cell line, Subject
View Samples