Filters
Technology
Platform
GSE51566
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Stroke is a leading cause of adult disability and death. Inflammation plays an important role in stroke pathology, but the factors which promote brain inflammation in this setting remain to be fully defined. Here we investigate the meninges, the membranes that envelop the brain, for a potential role in modulating immune cell trafficking to the brain. We also investigate the potential of mast cells (MCs) to modulate this response as MCs are often considered as 'first responders' playing a critical role in the initiation and development of inflammation in many disease settings. We find that stroke increases expression of inflammatory and immune response genes in the meninges in mice consistent with a potential role in modulating immune cell trafficking. Moreover, genetic and cell transfer approaches identify MCs as important modulators of this response.
Publication Title
Evidence that meningeal mast cells can worsen stroke pathology in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite education and aggressive treatment, breast cancer (BC) remains a clinical problem. BC cells (BCCs) can migrate early to metastatic sites where they may exist in cellular dormancy for decades. Presently, there are no consensus markers for cancer stem cells (CSCs) that are involved in tumor initiation and progression, and drug resistance. The current designation of CSCs might comprise similar tumor initiating cells, but at different developmental phase. In order to understand these differences, we developed a working hierarchy of BCCs. We initiated the studies in which three BCC subsets were selected based on the relative expressions of the stem cell-linked genes, Octamer4A (Oct4A). The sorted BCCs were subjected to array analyses using Affymetrix gene chip. Hierarchical clustering indicated distinct gene expression among the three subsets. Differential gene expressions of membrane proteins validated three novel genes, TMEM-98, GPR64 and FAT4. These three genes, in combination of known markers for CSCs, CD44, CD24, aldehyde dehydrogenase 1 (ALDH1) and Oct4A, were used to stratify BCCs led to a working hierarchy of BCCs. The validity of the hierarchical BCCs was applied to blood samples from patients, during relapse, and before and after treatment. These studies resulted in the patients grouped with distinct BCCs in the circulation. The relevance of the latter findings are discussed with regards to prediction of treatment response and time of BC relapse. The findings require a larger cohort of patients in a prospective multi-center study. The stratification could be important to understand treatment response, strategies for alternative approaches, and an understanding of the interaction between particular BCC subsets and the tissue microenvironment.
Publication Title
Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and the plastic storage of memories. DREAM /KChIP proteins form heterotetramers that bind DNA and repress transcription in a Ca2+-dependent manner. Single ablation of one member of the DREAM/KChIP family may result in a mild or the absence of phenotype due to partial gene compensation. To study the function of DREAM/KChIP proteins in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). We show that daDREAM controls the expression of several activity-dependent transcription factors including Npas4, Nr4a1, Mef2C, JunB and c-Fos, as well as the chromatin modifying enzyme Mbd4 and proteins related to actin polymerization like Arc and gelsolin. Thus, directly or through these targets, expression of daDREAM in the forebrain resulted in a complex phenotype characterized by i) impaired learning and memory, ii) loss of recurrent inhibition and enhanced LTP in the dentate gyrus without affecting Kv4-mediated potassium currents, and iii) modified spine density in DG granule neurons. Our results propose DREAM as a master-switch transcription factor regulating several activity-dependent gene expression programs to control synaptic plasticity, learning and memory.
Publication Title
DREAM controls the on/off switch of specific activity-dependent transcription pathways.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We evaluated transcriptional profiles in peripheral blood mononuclear cells (PBMCs) from 54 pregnant women in Kenya, 19 of whom delivered preterm.
Publication Title
Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Glucocorticoids are a well recognized and common cause of muscle atrophy. Glucocorticoid-induced atrophy can be prevented by testosterone, but the molecular mechanisms underlying such protection have not been described. Thus, the global effects of testosterone on dexamethasone-induced changes in gene expression were evaluated in rat gastrocnemius muscle using Affymetrix 230_2 DNA microarrays. Gene expression was analyzed after 7 days administration of dexamethasone, dexamethasone plus testosterone, or vehicle. Effects of these agents on weights of gastrocnemius muscles from these animals has been reported (1. Zhao W, Pan J, Zhao Z, Wu Y, Bauman WA, and Cardozo CP. Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol 110: 125-129, 2008.) Dexamethasone changed expression of 876 probe sets by at least 2-fold, of which 474 probe sets were changed by at least two fold in the opposite direction in the dexamethasone plus testosterone group (genes in opposition). Major biological themes represented by genes in opposition included IGF-1 signaling, protein synthesis, myogenesis and muscle development, and ubiquitin conjugases and ligases. Testosterone blocked increased expression of DDIT4 and eIF4EBP1, FOXO1 and of the p85 regulatory subunit of the IGF-1 receptor, while preventing decreased expression of IRS-1. Testosterone blocked decreased expression of LXR and suppressed upregulation of C/EBP beta and delta. Testosterone prevented increase expression of Cdkn1A (p21) and decrease expression of cyclins B and D, as well as many other changes that would be expected to reduce cell cycle progression. Testosterone prevented increased expression of muscle development factors Csrp3 and Mbn1 and blocked reduced expression of Wnt4. These data suggest that testosterone blocks multiple changes in gene expression that, collectively, would otherwise downregulate molecular signals that promote protein synthesis and muscle hypertrophy and that stimulate muscle protein catabolism.
Publication Title
REDD1 is a major target of testosterone action in preventing dexamethasone-induced muscle loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the gold standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.
Publication Title
A mesenchymal stromal cell gene signature for donor age.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Wnt signaling potentiates nevogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Melanocytes within benign human nevi are the paradigm for tumor suppressive senescent cells in a pre-malignant neoplasm. These cells typically contain mutations in either the BRAF or N-RAS oncogene and express markers of senescence, including p16. However, a nevus can contain 10s to 100s of thousands of clonal melanocytes and approximately 20-30% of melanoma are thought to arise in association with a pre-existing nevus. Neither observation is indicative of fail-safe senescence-associated proliferation arrest and tumor suppression. We set out to better understand the status of nevus melanocytes. Proliferation-promoting Wnt target genes, such as cyclin D1 and c-myc, were repressed in oncogene-induced senescent melanocytes in vitro, and repression of Wnt signaling in these cells induced a senescent-like state. In contrast, cyclin D1 and c-myc were expressed in many melanocytes of human benign nevi. Specifically, activated Wnt signalling in nevi correlated inversely with nevus maturation, an established dermatopathological correlate of clinical benignancy. Single cell analyses of lone epidermal melanocytes and nevus melanocytes showed that expression of proliferation-promoting Wnt targets correlates with prior proliferative expansion of p16-expressing nevus melanocytes. In a mouse model, activation of Wnt signaling delayed, but did not bypass, senescence of oncogene-expressing melanocytes, leading to massive accumulation of proliferation-arrested, p16-positive non-malignant melanocytes. We conclude that clonal hyperproliferation of oncogene-expressing melanocytes to form a nevus is facilitated by transient delay of senescence due to activated Wnt signaling. The observation that activation of Wnt signaling correlates inversely with nevus maturation, an indicator of clinical benignancy, supports the notion that persistent destabilization of senescence by Wnt signaling contributes to the malignant potential of nevi.
Publication Title
Wnt signaling potentiates nevogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
Illumina HiSeq 2500
Description
Dystonia is characterized by involuntary muscle contractions. Its many forms are genetically, phenotypically and etiologically diverse and it is unknown whether their pathogenesis converges on shared pathways. Mutations in THAP1, a zinc-finger transcription factor, cause DYT6, but its neuronal targets and functions are unknown. We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1C54Y or ?Exon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum. Enriched pathways and gene ontology terms include eIF2a Signaling, Mitochondrial Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and Synaptic Long Term Depression pathways, which are dysregulated in a genotype and tissue-dependent manner. Electrophysiological and neurite outgrowth assays confirmed the functional significance of those findings. Notably, several of these pathways were recently implicated in other forms of inherited dystonia, including DYT1. We conclude that dysfunction of these pathways may represent a point of convergence on the pathogenesis of unrelated forms of inherited dystonia. Overall design: We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1C54Y or deltaExon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum
Publication Title
Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 38 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We sorted for GFP+ cells using the enhancer trap J0571 with the UAS promoter driving the expression of different BIRD genes. Different genetic backgrounds are use and listed below.
Publication Title
Transcriptional control of tissue formation throughout root development.
Sample Metadata Fields
Specimen part
View Samples