Filters
Technology
Platform
GSE19610
Homo sapiens
29 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Epigenetic mechanisms contribute to deregulated gene expression of hematopoietic progenitors in Myelodysplastic Syndromes (MDS). Hypomethylating agents are able to improve peripheral cytopenias in MDS patients. To identify critical gene expression changes induced by hypomethylating agents, we analyzed gene expression profiling (GEP) of myelodysplastic and normal CD34+ hematopoietic stem cells treated in vitro with or without decitabine. Four MDS and two untreated early stage Hodgkins lymphomas were analyzed for GEP. Mock treated CD34+ stem cells segregate according to diagnosis and karyotype. After decitabine treatment, gene expression changes were more consistent on MDS CD34+ cells with abnormal kayotype. Comparing decitabine-induced genes with those found down-regulated in mock-treated MDS cells, we identified a list of candidate tumor suppressor genes in MDS. By real-time RT-PCR we confirmed expression changes for three selected genes CD9, CXCR4 and GATA2 in 12 MDS patients and 4 controls. CD9 was widely repressed in most MDS CD34+ cell samples, although similar levels of methylation were found in both normal and MDS total bone marrows. CXCR4 promoter methylation was absent in total bone marrows from 36 MDS patients. In conclusion, changes in gene expression changes induced by hypomethylating treatment are more pronounced in CD34+ cells from abnormal karyotype.
Publication Title
Gene expression profiling of myelodysplastic CD34+ hematopoietic stem cells treated in vitro with decitabine.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: Glioblastoma multiforme (GBM) is the most aggressive and most lethal primary malignant brain tumor, correlated with survival rates of less than one year from the time of diagnosis. Current surgical procedure attempts to remove the bulk of the tumor mass, whereas GBM frequently recurs within 1-3cm from the primary tumor resection site. Molecular mechanisms involved in the recurrence of the tumor are still poorly understood. The aim of the study was to define the molecular signature of GBM surrounding white matter (WM) in order to better understand the molecular mechanisms involved with tumor relapse.
Publication Title
Gene expression profile of glioblastoma peritumoral tissue: an ex vivo study.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Illumina HiSeq 4000
Description
Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq, we analyzed cellular diversity and lineage in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib. Overall design: Drop-Seq single-cell transcriptome sequencing of 15 mice: 5 Wild Type cerebella, 5 Drug-treated cerebellar tumors and 5 vehicle-treated cerebellar tumros.
Publication Title
scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We have performed conditional inactivation of mef2c in the anterior heart field (AHF) of mice and observed a phenotypic spectrum of outflow tract anomalies in the conditional mutant hearts. In an effort to identify misregulated genes in the outflow tracts of the mutants, we have performed RNA-Seq on outflow tract samples dissected from E10.5 mutant and wild-type embryos. Overall design: There are four wild-type samples and four mutant samples.
Publication Title
MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain, termed Madison (MSN), which naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Using a novel genomic enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes.
Publication Title
A new mouse model for mania shares genetic correlates with human bipolar disorder.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The transition from the non-maternal to the maternal state is characterized by a variety of CNS alterations that support the care of offspring. The septum (including lateral and medial portions) is a brain region previously linked to various emotional and motivational processes, including maternal care. In this study, we used microarrays (PLIER algorithm) to examine gene expression changes in the septum of postpartum mice and employed gene set enrichment analysis (GSEA) to identify possible regulators of altered gene expression. Genes of interest identified as differentially regulated with microarray analysis were validated with quantitative real-time PCR. We found that fatty acid binding protein 7 (Fabp7) and galanin (Gal) were downregulated, whereas insulin-like growth factor binding protein 3 (Igfbp3) was upregulated in postpartum mice compared to virgin females. These genes were previously found to be differentially regulated in other brain regions during lactation. We also identified altered expression of novel genes not previously linked to maternal behavior, but that could play a role in postpartum processes, including glutamate-ammonia ligase (Glul) and somatostatin receptor 1 (Sstr1) (both upregulated in postpartum). Genes implicated in metabolism, cell differentiation, or proliferation also exhibited altered expression. Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes. MicroRNAs have been linked to placenta and mammary gland development, but this is the first indication they may also play a key role in sculpting the maternal brain. Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period.
Publication Title
Gene expression changes in the septum: possible implications for microRNAs in sculpting the maternal brain.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Although Hematopoietic Stem Cell Transplantation (HSCT) routinely treats hematologic disease, many patients experience adverse outcomes. Understanding the molecular regulation of HSC engraftment is paramount to improving HSCT regimens. Here, we executed a large-scale transplant-based functional screen for novel regulators of HSC repopulation.. Of >50 gene candidates tested, 18 were required for in vivo hematopoietic repopulation and two were detrimental to repopulation, as their loss enhanced this activity. Each Hit was validated in a second screen. Eleven Hits have never before been implicated in HSC biology. We further show that one novel Hit, Foxa3, is required for optimal engraftment as Foxa3-/- bone marrow is defective in both primary and secondary hematopoietic reconstitution. We also present evidence that Foxa3 is a novel pioneer factor in HSC. Each gene identified in our screen is a window into the cellular mechanisms that control hematopoietic reconstitution. Thus, this work represents a resource to the community to better understand these processes
Publication Title
Functional screen identifies regulators of murine hematopoietic stem cell repopulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Coordinated gene expression changes across the CNS help to produce the mammalian maternal phenotype. Lateral septum (LS) is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum) in selectively bred maternal mice. Here, we expand on the prior study by 1) conducting microarray analysis solely on LS in virgin and postpartum mice, 2) using outbred mice, and 3) evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including nine GABAA receptor subunits (p<0.05). Subunits 4 and were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive 4/ containing receptor subtype. Conversely, subunits and were increased in maternal LS. Sixteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated), hypocretin receptor 1 (Hcrtr1), kappa opioid receptor 1 (Oprk1), and transient receptor potential channel 4 (Trpc4). Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C) motif ligand 12 (Cxcl12), fatty acid binding protein 7 (Fabp7), plasma membrane proteolipid (Pllp), and suppressor of cytokine signaling 2 (Socs2). Additional genes that are linked to anxiety, such as glutathione reductase (Gsr), exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.
Publication Title
Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 16 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The rapid evolution of toxin resistance in animals has important consequences for the ecology of species and our economy. Pesticide resistance in insects has been a subject of intensive study, however, very little is known about how Drosophila species became resistant to natural toxins with ecological relevance, such as -amanitin that is produced in deadly poisonous mushrooms. Here we performed a microarray study to elucidate the genes, chromosomal loci, molecular functions, biological processes, and cellular components that contribute to the -amanitin resistance phenotype in Drosophila melanogaster. We suggest that toxin entry blockage through the cuticle, phase I and II detoxification, sequestration in lipid particles, and proteolytic cleavage of -amanitin contribute in concert to this quantitative trait. We speculate that the resistance to mushroom toxins in Drosophila melanogaster and perhaps in mycophagous Drosophila species has evolved as a cross-resistance to pesticides or other xenobiotic substances.
Publication Title
The mechanisms underlying α-amanitin resistance in Drosophila melanogaster: a microarray analysis.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 24 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Recent research has highlighted that the polyphenols Quercetin (Q) and Tannic acid (TA) are capable of extending the lifespan of C. elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to Quercetin or Tannic acid concentrations that are non-effective (in lifespan extension), lifespan extending or toxic.
Publication Title
Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans.
Sample Metadata Fields
Specimen part, Treatment
View Samples