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Drosophila melanogaster
76 Downloadable Samples
Drosophila Gene 1.0 ST Array (drogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age. Here, we develop a comprehensive metric for physiological age in Drosophila, based on genome-wide expression profiling. We applied this metric to a model of adult-onset neurodegeneration, increased or decreased expression of the activating subunit of the Cdk5 protein kinase, encoded by the gene Cdk5, the ortholog of mammalian p35. Cdk5-mediated degeneration was associated with a 27-150% acceleration of the intrinsic rate of aging, depending on the tissue and genetic manipulation. Gene ontology analysis and direct experimental tests revealed that affected age-associated processes included numerous core phenotypes of neurodegeneration, including enhanced oxidative stress and impaired proteostasis. Taken together, our results suggest that Cdk5-mediated neurodegeneration results from accelerated aging, in combination with cell-autonomous neuronal insults. These data fundamentally recast our picture of the relationship between neurodegeneration and its most prominent risk factor, natural aging.
Publication Title
Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 40 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age. Here, we develop a comprehensive metric for physiological age in Drosophila, based on genome-wide expression profiling. We applied this metric to a model of adult-onset neurodegeneration, increased or decreased expression of the activating subunit of the Cdk5 protein kinase, encoded by the gene Cdk5, the ortholog of mammalian p35. Cdk5-mediated degeneration was associated with a 27-150% acceleration of the intrinsic rate of aging, depending on the tissue and genetic manipulation. Gene ontology analysis and direct experimental tests revealed that affected age-associated processes included numerous core phenotypes of neurodegeneration, including enhanced oxidative stress and impaired proteostasis. Taken together, our results suggest that Cdk5-mediated neurodegeneration results from accelerated aging, in combination with cell-autonomous neuronal insults. These data fundamentally recast our picture of the relationship between neurodegeneration and its most prominent risk factor, natural aging.
Publication Title
Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 66 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Murine testis developmental time course created from tissue samples collected from birth through adulthood and hybridized to MGU74v2 A, B, and C chips in duplicate
Publication Title
The murine testicular transcriptome: characterizing gene expression in the testis during the progression of spermatogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Pharmacological inhibition of cyclooxygenase-2 (COX-2) is being explored as a chemotherapeutic option because COX-2 protein expression is often elevated in many cancers. Cancer cells treated with COX-2 inhibitors, such as the selective COX-2 inhibitor celecoxib, show growth inhibition and the induction of apoptosis, through alterations in inflammatory processes, angiogenesis, cell adhesion and transforming growth factor- signaling. This study was conducted to determine if the same processes are relevant to celecoxibs effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomized to receive a 7-day course of celecoxib (400 mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from patients with and without celecoxib pre-treatment. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. Of the differentially expressed genes, multiple genes involved in cellular lipid and glutathione metabolism showed decreased expression levels in celecoxib pre-treated samples; changes associated with diminished cellular proliferation. Other observed gene expression changes consistent with reduced proliferation include: altered expression of genes involved in cell adhesion (including collagen, laminin, von Willebrand factor and tenascin C), increased expression of inflammatory modulators (including inerleukin-6, S100 calcium binding protein A8, and several chemokines) and decreased expression of the pro-angiogenic gene, angiogenin. Celecoxib pre-treatment for 7 days in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation.
Publication Title
Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation.
Sample Metadata Fields
Sex, Disease stage, Treatment
View Samples
GSE19320- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Gene expression profiling of zebrafish early eye development on 3 to 5 days post fertilization (dpf)
Publication Title
Integrating multiple genome annotation databases improves the interpretation of microarray gene expression data.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3 gene, which encodes a deubiquitinating enzyme, ATXN3, implicated in numerous quality control pathways. Several mechanisms have been proposed to explain the pathogenic role of mutant polyQ-expanded ATXN3 in SCA3 including disease protein aggregation, impairment of ubiquitin-proteasomal degradation and transcriptional dysregulation. A better understanding of the normal functions of this protein may shed light on SCA3 disease pathogenesis. To assess the potential normal role of ATXN3 in regulating transcription, we compared gene expression profiles in wildtype (WT) versus Atxn3 knockout (KO) mouse embryonic fibroblasts (MEFs).
Publication Title
Loss of the Spinocerebellar Ataxia type 3 disease protein ATXN3 alters transcription of multiple signal transduction pathways.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hepatic drug metabolism plays a key role in determining drug response and safety. Studies of drug metabolism generate valuable information about regulation of genes encoding drug-metabolizing enzymes and enzyme functions that are critical in developing dosing guideline. However, current knowledge is insufficient to support dosing guideline for pregnant women. Specifically, substrates of a major drug-metabolizing enzyme CYP2D6 show increased elimination during pregnancy, but the underlying mechanisms are completely unknown largely due to a lack of experimental models. Here, we introduce CYP2D6-humanized (Tg-CYP2D6) mice as an animal model where hepatic CYP2D6 expression is increased during pregnancy, recapitulating the clinically reported changes in CYP2D6-mediated drug metabolism. In these mice, pregnancy had minimal effects on the expression of hepatocyte nuclear factor (HNF) 4a, the transcription factor controlling basal CYP2D6 expression. Krppel-like factor (KLF) 9 and small heterodimer partner (SHP) were found up- and down-regulated in Tg-CYP2D6 mouse livers during pregnancy, respectively. KLF9 enhanced HNF4a-mediated transactivation of the CYP2D6 promoter whereas SHP repressed it. Retinoic acid (RA), an endogenous compound that induces SHP, exhibited decreased hepatic levels during pregnancy. These results indicate that interplay among hepatic transcription factors HNF4a, SHP, and KLF9 underlies CYP2D6 induction during pregnancy, and that retinoic acid is a potential trigger. This is the first report on the mechanisms underlying CYP2D6 induction and illustrates the utility of humanized mice as an in vivo model to study altered drug disposition during pregnancy.
Publication Title
Krüppel-like factor 9 promotes hepatic cytochrome P450 2D6 expression during pregnancy in CYP2D6-humanized mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Identification of imprinted genes expressed in adult CD3+ splenocytes
Publication Title
Hematopoietic reconstitution with androgenetic and gynogenetic stem cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
Illumina HiSeq 2500
Description
The Polycomb Repressive Complex 2 (PRC2) is composed of core subunits SUZ12, EED, RBBP4/7 and EZH1/2, which together are responsible for all di- and tri- methylation of lysine 27 on Histone H3 (H3K27me2/3) in higher eukaryotes. While two distinct forms, PRC2.1 (containing one Polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2) exist, little is known about their differential functions or interplay. Here we report the discovery of a new family of vertebrate specific PRC2.1 associated proteins; 'PRC2 associated LCOR isoform 1' (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively. PALI1 promotes PRC2 methyltransferase activity in vitro and in vivo and is essential for mouse development. We uncover an antagonistic relationship between the PALI-PRC2.1 and AEBP2-PRC2.2 subtypes and establish that both are required for balanced regulation of Polycomb target genes during differentiation. This discovery links the Polycomb epigenetic system with co-repressors and nuclear receptors in the regulation of cellular identity. Overall design: RNA seq analysis of Pali WT, Pali1 KO, Pali1/2 double KO, C129 WT and Aebp2 gene trap mouse embryonic stem cells at three time points (Day 0, Day 4 and Day 8) during embryoid body differentiation (EB). 30 samples are included. Biological duplicates are present.
Publication Title
A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.
Sample Metadata Fields
Specimen part, Subject
View Samples