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GSE36229
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose: Klf5 plays a critical role in the mouse ocular surface (Kenchegowda et al., 2011. Dev Biol. 356:5-18). Here, we compare wild-type (WT) and Klf5-conditional null (Klf5CN) corneal gene expression at postnatal day-11 (PN11) and PN56 to identify the Klf5-target genes. Methods: Gene expression was compared using Affymetrix microarrays with QPCR validation. Transient transfection assays examined the effect of Klf5 on selected target gene promoter activities. Whole-mount corneal immunofluorescent staining examined neovascularization and CD45+ macrophage influx. Results: Expression of 714 and 753 genes was increased, and 299 and 210 genes decreased in PN11 and PN56 Klf5CN corneas, respectively, with 366 concordant increases, 72 concordant decreases and 3 discordant changes. Canonical pathway analysis identified 35 and 34 significantly (p<0.001) enriched pathways at PN11 and PN56, respectively, with 24 common pathways. PN56 Klf5CN corneas shared 327 increases and 91 decreases with the previously described Klf4CN corneas (Swamynathan et al., 2008. IOVS 49:3360-70). Angiogenesis and immune response-related genes were affected consistent with lymphangiogenesis and macrophage influx in Klf5CN corneas, respectively. Expression of 1574 genes was increased and 1915 decreased, in the WT PN56 compared with PN11 corneas. Expression of many collagens, matrix metalloproteinases and other extracellular matrix associated genes decreased in WT corneas between PN11 and PN56, while that of solute carrier family members increased. Conclusions: Differences in PN11 and PN56 corneal Klf5-target genes reveal dynamic changes in Klf5 functions during corneal maturation. Klf4- and Klf5-target genes do not overlap, consistent with their non-redundant roles in the mouse cornea.
Publication Title
Critical role of Klf5 in regulating gene expression during post-eyelid opening maturation of mouse corneas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Conditional disruption of Klf4 in the ectoderm-derived tissues of the eye results in defective cornea, conjunctiva and the lens.
Publication Title
Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 7 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
To identify genes regulated by Rx3 during optic vesicle morphogenesis, adult zebrafish carriers of a null rx3 mutation were mated. Before 13 hours post fertilization (hpf), the earliest time point at which optic vesicle evagination phenotypes could be reliably detected, offspring were phenotypically separated into pools comprising of mutants with an absence of optic vesicles or siblings exhibiting a wild-type phenotype. Three replicates of pooled RNA samples from 13 hpf eyeless mutants (rx3-/-) or phenotypically wild-type siblings (rx3+/+ or rx3+/-), and one replicate of 13 hpf wild-type zebrafish larva were collected for whole transcriptome sequencing. Overall design: Whole transcriptome sequencing (RNA-seq) was performed on zebrafish rx3-/- mutants, wild-type siblings and wild-type AB strains at 13 hpf
Publication Title
Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
TCDD increased expression of numerous differentiation specific genes and decreased expression of numerous genes involved in mitochondrial health and redox homeostasis
Publication Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We recently identified pathogenic KIF1Bb mutations in sympathetic nervous system malignancies that are defective in developmental apoptosis. Here we deleted KIF1Bb in the mouse sympathetic nervous system based on a cre recombination system driven by the dopamine beta hydroxylase (DBH) promoter. We observed impaired sympathetic nervous function and misexpression of genes required for sympathoadrenal lineage differentiation in KIF1Bb deficient sympathetic ganglia. Overall design: We analyzed superior cervical ganglia from post-natal day 1 mice. We compared ganglia from four wild-type control animals (KIF1Bb fl/fl) with ganglia from four animals with conditional knockout of KIF1Bb (KIF1Bb fl/fl : DBHcre +/-).
Publication Title
Neuroblast differentiation during development and in neuroblastoma requires KIF1Bβ-mediated transport of TRKA.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
During development neuronal progenitors compete for growth factors such as nerve growth factor NGF and require the prolyl hydroxylase EglN3 and the kinesin KIF1Bß for developmental apoptosis. Inherited KIF1Bß loss-of-function mutations in neuroblastomas and pheochromocytomas implicate KIF1Bß as a 1p36.2 tumor suppressor, however the mechanism of tumor suppression is unknown. We found that KIF1Bß interacts with the RNA helicase A (DHX9) resulting in DHX9 nuclear accumulation to regulate apoptosis. KIF1Bß-dependent DHX9 nuclear localization leads to transcription of the apoptotic target XIAP-associated factor 1. DHX9 is induced when NGF is limiting and required for apoptosis in cells deprived of NGF. Overall design: NB1 cells were transduced to incorporate shRNA against DHX9 or a scrambled control, and transfected with a KIF1Bß expression vector or control, then transfected cells were isolated and lysed after 48h.
Publication Title
RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic a and b cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase b cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify a, b, and d cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the sub-populations by flow cytometry and, using next generation RNA sequencing, we report on the detailed transcriptomes of fetal and adult a and b cells. We observed that human islet composition was not influenced by age, gender, or body mass index and transcripts for inflammatory gene products were noted in fetal b cells. In addition, within highly purified adult glucagon-expressing a cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet a and b cell subsets from fetal and adult pancreata offers clear implications for strategies that seek to increase insulin expression in type 1 and type 2 diabetes. Overall design: RNA-sequencing of highly purified human adult and fetal islet cell subset was performed using our newly developed method. Using this data, we can study and compare the detailed transcriptome or alpha and beta cells during development.
Publication Title
Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq1000
Description
The detachment of epithelial cells, but not cancer cells, causes anoikis due to reduced energy production. Invasive tumor cells generate three splice variants of the metastasis gene osteopontin. The cancer-specific form osteopontin-c supports anchorage-independence through inducing oxidoreductases and upregulating intermediates/enzymes in the hexose monophosphate shunt, glutathione cycle, glycolysis, glycerol phosphate shuttle, and mitochondrial respiratory chain. Osteopontin-c signaling upregulates glutathione (consistent with the induction of the enzyme GPX-4), glutamine and glutamate (which can feed into the tricarboxylic acid cycle). Consecutively, the cellular ATP levels are elevated. The elevated creatine may be synthesized from serine via glycine and also supports the energy metabolism by increasing the formation of ATP. Metabolic probing with N-acetyl-L-cysteine, L-glutamate, or glycerol identified differentially regulated pathway components, with mitochondrial activity being redox dependent and the creatine pathway depending on glutamine. The effects are consistent with a stimulation of the energy metabolism that supports anti-anoikis. Our findings imply a synergism in cancer cells between osteopontin-a, which increases the cellular glucose levels, and osteopontin-c, which utilizes this glucose to generate energy. Overall design: mRNA profiles of MCF-7 cells transfected with osteopontin-a, osteopontin-c and vector control were generated by RNA-Seq, in triplicate, by Illumina HiSeq.
Publication Title
Energy metabolism during anchorage-independence. Induction by osteopontin-c.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Cone photoreceptors are specialised sensory retinal neurons responsible for photopic vision, colour perception and visual acuity. Retinal degenerative diseases are a heterogeneous group of eye diseases in which the most severe vision loss typically arises from cone photoreceptor dysfunction or degeneration. Establishing a method to purify cone photoreceptors from retinal tissue can accelerate the identification of key molecular determinants that underlie cone photoreceptor development, survival and function. The work herein describes a new method to purify enhanced green fluorescent protein (EGFP)-labelled cone photoreceptors from adult retina of Tg(3.2TCP:EGFP) zebrafish. Electropherograms confirmed downstream isolation of high-quality RNA with RNA integrity number (RIN) >7.6 and RNA concentration >5.7 ng/l obtained from both populations. Reverse Transcriptase-PCR (RT-PCR) confirmed that the EGFP-positive cell populations express known genetic markers of cone photoreceptors that were not expressed in the EGFP-negative cell population. This work is an important step towards the identification of cone photoreceptor-enriched genes, protein and signalling networks responsible for their development, survival and function. In addition, this advancement facilitates the identification of novel candidate genes for inherited human blindness.
Publication Title
HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Keap1/Nrf2 signaling pathway is a tractable target for the pharmacological prevention of tumorigenesis. 3H-1,2-dithiole-3-thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are representative members of two classes of Nrf2-activating chemopreventive agents. Natural dithiolethiones have been widely used in clinical trials for cancer chemoprevention. Synthetic triterpenoids, however, have been shown to be significantly more potent Nrf2 activators and are under clinical evaluation for the treatment of chronic kidney disease. This study seeks to characterize the structure-activity relationship between D3T and CDDO-Im in mouse liver tissue. To this end we treated Wt and Nrf2-null mice with 300 umol/kg bw D3T and 3, 10, and 30 umol/kg bw CDDO-Im every other day for 5 days and evaulated global gene expression changes as a product of both treamtent and genotype using Affymetrix microarray.
Publication Title
Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify Common and Unique Gene, Protein, and Pathway Responses In Vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples