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SRP044640
Mus musculus
5 Downloadable Samples
Illumina HiSeq 2000
Description
Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Overall design: RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.
Publication Title
Altered enhancer transcription underlies Huntington's disease striatal transcriptional signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Ion Torrent Proton
Description
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (Doublecortin-like kinase 3) which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington''s disease. Recent data obtained in studies related to cancer suggest DCLK3 could have anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington''s disease may render striatal neurons more susceptible to mutant huntingtin (mHtt). We discovered that DCLK3 silencing in the striatum of mice exacerbated the toxicity of an N-terminal fragment of mHtt. Conversely, overexpression of DCLK3 reduced neurodegeneration produced by mHtt. DCLK3 also produced beneficial effects on motor symptoms in a knock-in mouse model of Huntington''s disease. Using different mutants of DCLK3, we found that the kinase activity of the protein plays a key role in neuroprotection. To investigate the potential mechanisms underlying DCLK3 effects, we studied the transcriptional changes produced by the kinase domain in human striatal neurons in culture. Results show that DCLK3 regulates in a kinase-dependent manner the expression of many genes involved in transcription regulation and nucleosome/chromatin remodeling. Consistent with this, histological evaluation showed DCLK3 is present in the nucleus of striatal neurons and, protein-protein interaction experiments suggested that the kinase domain interacts with zinc finger proteins, including TADA3, a core component of SAGA complex. Our novel findings suggest that the presence of DCLK3 in striatal neurons may play a key role in transcription regulation and chromatin remodeling in these brain cells, and show that reduced expression of the kinase in Huntington's disease could render the striatum highly vulnerable to neurodegeneration. Examination of DCLK3 as neuroprotector against mutant huntingtin in vivo and in vitro models. Overall design: Examination of DCLK3 as neuroprotector against mutant huntingtin in vitro experiments.
Publication Title
The striatal kinase DCLK3 produces neuroprotection against mutant huntingtin.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Natural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy.
Publication Title
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Saccharomyces cerevisiae
- 19 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Publication Title
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Sample Metadata Fields
Age
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Publication Title
Significant and systematic expression differentiation in long-lived yeast strains.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We conducted a genome-wide expression analysis of wild-type males using three cell populations isolated from mitotic, meiotic and post-meiotic phases of spermatogenesis in Drosophila melanogaster. Our approach was to directly isolate testis regions enriched with RNAs from each of the three specific germline phases.
Publication Title
Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
TGFbeta induces VSMC gene expression in human coronary artery smooth muscle cell (HCASM) Overall design: Subconfluent human coronary artery smooth muscle cells (HCASM) were starved overnight followed by TGFbeta treatment for 24 hours. RNA was then extracted for deep-sequencing.
Publication Title
Transforming growth factor β1 suppresses proinflammatory gene program independent of its regulation on vascular smooth muscle differentiation and autophagy.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Transcriptome analysis of RNA samples from riboflavin-depleted HEK293T cells.
Publication Title
Riboflavin Depletion Promotes Tumorigenesis in HEK293T and NIH3T3 Cells by Sustaining Cell Proliferation and Regulating Cell Cycle-Related Gene Transcription.
Sample Metadata Fields
Cell line
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Gene 1.0 ST Array (chigene10st)
Description
Integrins have long been known to have a role in adhesion of neural stem cells within the neuroepithelium, but little is known about their role in regulating stem cell behaviour through signalling. We aimed to investigate the effect of integrin-beta 1 signalling (itgb1) on these cells by transfection of a constitutively active itgb1. This creates a heterogenous pattern of expression allowing the study of cell-autonomous and non-cell autonomous effects.
Publication Title
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The human steroid receptor RNA activator (SRA) gene encodes both non-coding RNAs (ncRNAs) and protein-generating isoforms. However, the breadth of endogenous target genes that might be regulated by SRA RNAs remains largely unknown. To address this, we depleted SRA RNA in two human cancer cell lines (HeLa and MCF-7) with small interfering RNAs, then assayed for changes in gene expression by microarray analyses using Affymetrix HGU133+2 arrays. We also tested if SRA depletion affects estradiol-regulated genes in MCF-7 breast cancer cells.
Publication Title
Research resource: expression profiling reveals unexpected targets and functions of the human steroid receptor RNA activator (SRA) gene.
Sample Metadata Fields
Cell line
View Samples