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GSE57695
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and re-populate the tumor. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and re-activation. In this study we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state which is switched on by engagement with bone lining cells or osteoblasts, and switched off by osteoclasts remodeling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy targeting dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Publication Title
Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Endoplasmic reticulum-associated degradation (ERAD) represents a principle quality control (QC) mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unknown. Here we discover that IRE1alpha, the sensor of unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex. Mechanistically, ERAD-mediated IRE1alpha degradation occurs in a Bip-dependent manner under basal conditions and is attenuated in response to ER stress. Both intramembrane hydrophilic residues of IRE1alpha and lectin protein OS9 are required for IRE1alpha degradation. ERAD deficiency causes IRE1alpha protein stabilization, accumulation and mild activation both in vitro and in vivo, leading to cellular hypersensitivity to ER stress and inflammation. Furthermore, though enterocyte-specific Sel1L-knockout mice (Sel1LIEC) are viable and appear normal, they are more susceptible to experimental colitis in an IRE1alpha-dependent but CHOP-independent manner. Collectively, these results demonstrate that Sel1L-Hrd1 ERAD serves a distinct, essential function in restraint of IRE1alpha signaling in vivo by managing its protein turnover.
Publication Title
IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
To assess the effect of activation of the unfolded protein response (UPR) in colon cancer cell lines, we treated cells with the AB5 subtilase cytotoxin (SubAB). This proteolytically cleaves the 78-kDa glucose-regulated protein (GRP78; also known as HSPA5 or BiP) inside the endoplasmic reticulum. We find that the WNT signaling pathway is highly affected upon treatment with SubAB.
Publication Title
ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Malignant Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-B signaling cascades. We depleted subunit combinations corresponding to either canonical (p50/RelA) or non-canonical (p52/RelB) dimers in the HL cell line L-1236 and performed Affymetrix microarray analysis. Knockdown of p52/RelB affected the expression of a significantly higher number of genes than the knockdown of p50/RelA. The two sets of target genes presented a partial overlap, however they also revealed specific genes that are involved in distinct aspects of tumor biology.
Publication Title
A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Malignant cells of Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-B signaling cascades. Knockdown of a subunit combination corresponding to the non-canonical NF-B dimer (p52/RelB) in the HL cell line L-1236 caused up-regulation of a set of genes that are associated with hematopoietic and lymphoid organ development. As p52 can form homodimeric complexes, which can repress transcription either alone or in association with transcriptional repressors such as HDAC1, we knocked down p52 alone to analyze its role in gene repression in HL cells. We found that the single knockdown of p52 is indeed sufficient to up-regulate an interesting set of genes that may play a role in B-cell and/or HL development.
Publication Title
A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei are important integrative structures that regulate co-ordinated responses to perturbations in cardiovascular homeostasis. Through descending projections from parvocellular neurons to the brainstem, the PVN acts as an autonomic 'premotor nucleus', regulating reflex changes in sympathetic nerve activity that are involved in blood pressure and blood volume regulation. Endocrine responses are mediated through axonal projections from SON and PVN magnocellular neurons (MCNs) to the capillaries of the posterior pituitary neural lobe. In response to dehydration, a massive release of the antidiuretic peptide hormone vasopressin (VP) into the circulation is accompanied by a dramatic functional remodelling of the HNS. We have used microarrays to comprehensively catalogue the genes expressed in the PVN, the SON and the neurointermediate lobe (NIL) of the pituitary gland. Further, we have identified transcripts that are regulated as a consequence of dehydration, as well as RNAs that are enriched in either the PVN or the SON. We suggest that these differentially expressed genes represent candidate regulators and effectors of HNS activity and remodelling.
Publication Title
A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We have used microarrays to comprehensively describe the transcriptomes of the supraoptic nucleus (SON), the paraventricular nucleus (PVN) and the neurointermediate lobe (NIL) of adult male Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats, as well as the paraventricular nucleus of Wistar (WIST) rats. Comparison of these gene lists has enabled us to identify surprisingly large differences in hypothalamo-neurohypophyseal system gene expression patterns in these three strains. We have also shown that different transcript populations are enriched in the PVN and the SON of SD and WKY rats. The transcriptome differences catalogued here may be molecular substrates for the neuro-humoral phenotypic differences exhibited by different strains of rats.
Publication Title
The transcriptome of the rat hypothalamic-neurohypophyseal system is highly strain-dependent.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 23 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The area postrema (AP) is a sensory circumventricular organ characterised by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague Dawley (SD) and Wistar Kyoto (WKY) rat and present here a comprehensive catalogue of gene expression, focussing specifically on the population of ion channels, receptors and G protein-coupled receptors (GPCRs) expressed in this sensory tissue; of the GPCRs expressed in the rat AP we identified ~36% that are orphans having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72-hours dehydration (DSD) and 48-hours fasting (FSD) and have performed microarrays under these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat (SHR) AP compared to the normotensive WKY controls however. Finally, analysis of these hypertension-related elements revealed genes that are involved in both the regulation of blood pressure and immune function and as such are excellent targets for further study.
Publication Title
The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Gallus gallus
- 20 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Relative levels of RNA transcripts were compared between anterior and posterior wing bud thirds from stage HH24 normal and talpid3 mutant chicken embryos using chicken Affymetrix chips. Data collected with Affymetrix scanner was normalized using the Plier algorithm within the expression console package from Affymetrix and log2 transformed. 5 replicates of anterior third normal wing buds, 4 replicates of posterior third of normal wing buds and 4 replicates each of anterior and posterior thirds of talpid3 wing buds at stage HH24 were examined.
Publication Title
Identification of genes downstream of the Shh signalling in the developing chick wing and syn-expressed with Hoxd13 using microarray and 3D computational analysis.
Sample Metadata Fields
Age, Specimen part
View Samples