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GSE48104
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Deregulated intracellular Ca2+ homeostasis underlies synaptic dysfunction and is a common feature in neurodegenerative processes, including Huntington's disease (HD). DREAM/calsenilin/KChIP-3 is a multifunctional Ca2+ binding protein that controls the expression level and/or the activity of several proteins related to Ca2+ homeostasis, neuronal excitability and neuronal survival. We found that expression of endogenous DREAM (DRE antagonist modulator) is reduced in the striatum of R6 mice, in STHdh-Q111/111 knock in striatal neurons and in HD patients. DREAM down regulation in R6 striatum occurs early after birth, well before the onset of motor coordination impairment, and could be part of an endogenous mechanism of neuroprotection, since i) R6/2 mice hemizygous for the DREAM gene (R6/2xDREAM+/-) showed delayed onset of locomotor impairment and prolonged lifespan, ii) motor impairment after chronic administration of 3-NPA was reduced in DREAM knockout mice and enhanced in daDREAM transgenic mice and, iii) lentiviral-mediated DREAM expression in STHdh-Q111/111 knock in cells sensitizes them to oxidative stress. Transcriptomic analysis showed that changes in gene expression in R6/2 striatum were notably reduced in R6/2xDREAM+/- striatum. Chronic administration of repaglinide, a molecule able to bind to DREAM in vitro and to accelerate its clearance in vivo, delayed the onset of motor dysfunction, reduced striatal loss and prolonged the lifespan in R6/2 mice. Furthermore, exposure to repaglinide protected STHdh-Q111/111 knock in striatal neurons sensitized to oxidative stress by lentiviral-mediated DREAM overexpression. Thus, genetic and pharmacological evidences disclose a role for DREAM silencing in early neuroprotective mechanisms in HD.
Publication Title
Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 15 Downloadable Samples
Illumina HiSeq 1500
Description
UV-B radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibits maize leaf growth without causing any other visible stress symptoms, including accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth is a consequence of a reduction in cell production, and a shortened growth zone (GZ) in UV-B irradiated leaves. To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including Growth Regulating Factors (GRFs) and transcripts for proteins participating in different hormone pathways. Overall design: Factorial design with two factors: Treatment (control vs UV-B) x Zone I (0-1cm from base of the leaf), 2 (1-2cm from base of the leaf) and 3 (2-3cm from base of the leaf), 3 replicates
Publication Title
UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from Ahr-knockout and wild-type mice. HSC from young-adult (8 wk old) AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.
Publication Title
Loss of aryl hydrocarbon receptor promotes gene changes associated with premature hematopoietic stem cell exhaustion and development of a myeloproliferative disorder in aging mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Using a mouse model overexpressing human SNCA and profiling the striatal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through chronic unpredictable mild stress (CUMS) exposure. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of chronic unpredictable mild stress (CUMS) with standard housing conditions. Employing RNA-seq, we profiled gene expression in the striatum of 6-month-old female animals.
Publication Title
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
Using a mouse model overexpressing human SNCA and profiling the striatal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through chronic unpredictable mild stress (CUMS) exposure. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of chronic unpredictable mild stress (CUMS) with standard housing conditions. Employing RNA-seq, we profiled gene expression in the striatum of 6-month-old female animals.
Publication Title
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
After co-evolving with humans, its only major host, Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication, yet elicits enough immunopathology to ensure its transmission. Here, we provide evidence that this balance is regulated in part by a previously uncharacterized, cytosolic, membrane-associated protein with a novel structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity and quality of Mtb-derived membrane vesicles bearing TLR2 ligands, including the lipoproteins LpqH and SodC. We propose that rv0431 be named virR (vesiculogenesis and immune response regulator). To our knowledge, VirR is the first bacterial protein identified to regulate vesiculogenesis. Overall design: Transcriptome sequencing of mouse macrophages uninfected, infected with WT Mtb, or infected with rv0431 mutant Mtb.
Publication Title
Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Using a mouse model overexpressing human SNCA and profiling the hippocampal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through long-term enriched environment (EE) exposure. We observed that EE prevented perturbations of genes attributed to neuronal and glial cell types and linked to glutamate signaling, calcium homeostasis, inflammation, and related processes of SNCA biology. Cluster and promoter analyses suggested driver genes that specifically responded to the EE, and pointed to a pivotal role of Egr1 to have hierarchically activated other drivers. We suggest a model in which EE-induced driver genes prevent and counter-balance perturbations of SNCA overexpression, restoring a largely normalized gene expression profile and system state. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of a long-term EE with standard housing conditions. Employing RNA-seq, we profiled gene expression in the hippocampus of 12-month-old female animals.
Publication Title
Environmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Human infection with Cryptococcus neoformans (Cn), a prevalent fungal pathogen, occurs by inhalation and deposition in the lung alveoli of infectious particles. The subsequent host pathogen interaction is multifactorial and can result either in eradication, latency or extra-pulmonary dissemination. Successful control of Cn infection is dependent on host macrophages as shown by numerous studies. However in vitro macrophages display little ability to kill Cn. Recently, we reported that ingestion of Cn by macrophages induces early cell cycle progression that is subsequently followed by mitotic arrest, an event that almost certainly reflects damage to the host cell. The goal of the present work was to understand macrophage pathways affected by Cn toxicity. Infection of J774.16 macrophage-like cell line macrophages by Cn in vitro was associated with changes in gene pattern expression. Concomitantly we observed depolarization of macrophage mitochondria and alterations in protein translation rate. Our results indicate that Cn infection impairs multiple host cellular functions. Therefore we conclude Cn intracellular residence in macrophages undermines the health of these critical phagocytic cells interfering with their ability to clear the fungal pathogen.
Publication Title
Macrophage mitochondrial and stress response to ingestion of Cryptococcus neoformans.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regional localization within the bone marrow influences the functional capacity of human HSCs.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Demonstration of hematopoietic stem cells (HSCs) was first shown in the mouse and was dependent on recipient bone marrow (BM) to support in vivo multilineage hematopoietic reconstitution, thereby illustrating non-cell-autonomous requirements for HSC functions. Murine studies have defined microanatomic compartments in the BM comprised of osteoblasts, mesenchymal cells, subsets of vasculature, and innervating neural cells functioning as an HSC-supportive niche. Despite the potential clinical applications, analyses of putative HSCs in the BM of humans has not been examined. Here, using human bone biopsies, we provide evidence of HSC propensity to endosteal regions of Trabecular Bone Area (TBA). Independent of phenotypic definitions based on prospective isolation, functional studies indicate that human HSCs residing in the TBA of human and transplanted recipients had superior regenerative and self-renewal capacity and are molecularly distinct to those repopulating the Long Bone Area (LBA). Consistent with the non-cell-autonomous nature of HSC function, osteoblasts in the TBA possess unique characteristics and expressed a key network of factors including those involving Notch activity which could regulate TBA vs. LBA location of human HSCs in vivo. Our study illustrates that human-mouse xenografts provide a surrogate to indigenous human HSC in the BM, and demonstrates that BM architecture plays a critical role in defining functional properties of human HSCs.
Publication Title
Regional localization within the bone marrow influences the functional capacity of human HSCs.
Sample Metadata Fields
Specimen part
View Samples