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GSE29641
Homo sapiens
23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and help with patient prognosis.
Publication Title
The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression signatures in breast cancer.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
Histone H3.3 is a highly conserved histone H3 replacement variant in metazoans, and has been implicated in many important biological processes including cell differentiation and reprogramming. Germline and somatic mutations in H3.3 genomic incorporation pathway components, or in H3.3 encoding genes, have been associated with human congenital diseases and cancers, respectively. However, the role of H3.3 in mammalian development remains unclear. To address this question, we generated H3.3 null mouse models through classical genetic approaches. We found H3.3 plays an essential role in mouse development. Complete depletion of H3.3 leads to developmental retardation and early embryonic lethality. At the cellular level, H3.3 loss triggers cell cycle suppression and cell death. Surprisingly, H3.3 depletion does not dramatically disrupt gene regulation in the developing embryo. Instead, H3.3 depletion causes dysfunction of heterochromatin structures at telomeres, centromeres and pericentromeric regions of chromosomes leading to mitotic defects. The resulting karyotypical abnormalities and DNA damage lead to p53 pathway activation. In summary, our results reveal that an important function of H3.3 is to support chromosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. Overall design: RNA-seq in embryos at E10.5 comparing 3 samples with the following genotype Trp53-/-; H3f3afl/-; H3f3bfl/-; Sox2-CreTg/0 to three samples with the following genotype Trp53-/-; H3f3afl/+; H3f3bfl/+; Sox2-CreTg/0
Publication Title
Histone H3.3 maintains genome integrity during mammalian development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Of the thousands of long non-coding RNAs expressed in embryonic stem (ES) cells, few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency or reprogramming somatic cells to the pluripotent state. In ES cells, Cyrano is a stably expressed long intergenic non-coding RNA with no previously assigned role. We demonstrate that Cyrano contributes to ES cell maintenance, as its depletion results in loss of hallmarks of self-renewal. Delineation of Cyrano''s network through transcriptomics revealed widespread effects on signaling pathways and gene expression networks that contribute to ES cell maintenance. Cyrano shares unique sequence complementarity with the differentiation-associated microRNA, mir-7, and mir-7 overexpression reduces expression of a key self-renewal factor to a similar extent as Cyrano knockdown. This suggests that Cyrano functions to restrain the action of mir-7. Altogether, we provide a view into the multifaceted function of Cyrano in ES cell maintenance. Overall design: RNA-seq on mouse R1 embryonic stem (ES) cells with two biological replicates transfected with an shRNA knockdown of Cyrano and two biological replicates transfected with a non-targeting control vector.
Publication Title
Long Noncoding RNA Moderates MicroRNA Activity to Maintain Self-Renewal in Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Topoisomerases facilitate transcription of long genes linked to autism.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology.
Publication Title
Topoisomerases facilitate transcription of long genes linked to autism.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology. Overall design: [Mouse] 5 biological replicates of transcriptome sequencing (RNAseq) from topotecan treated neurons and vehicle treated controls; Pol2 ChIPseq of topotecan and vehicle treated neurons [Human] Transcriptome sequencing (RNAseq) from topotecan treated neurons and vehicle treated control.
Publication Title
Topoisomerases facilitate transcription of long genes linked to autism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Ovarian clear cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a genetically engineered mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumors with OCCC-like histopathology, culminating in hemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolonged mouse survival by inhibiting tumor cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signaling in OCCC pathogenesis. We further show that ARID1A-PIK3CA mutations cooperate to promote tumor growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodeling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signaling. We propose that ARID1A protects against inflammation-driven tumorigenesis.
Publication Title
Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human umbilical vein endothelial cells (HUVECs) formed capillary structures when co-cultured with normal human dermal fibroblasts (NHDFs). HUVEC competence and NHDF supportiveness of cord formation were found to be highly cell-passage dependent with the early passage cells forming more angiogenic cord structures. We thus profiled gene expression in NHDFs with different passages to understand the molecular mechanisms underlying the in vitro angiogenesis control.
Publication Title
Developing and applying a gene functional association network for anti-angiogenic kinase inhibitor activity assessment in an angiogenesis co-culture model.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Protein deficiency and intestinal parasite infection during pregnancy impair fetal growth through passage of signals from the maternal environment which signal impairment of fetal growth. The placenta is an important regulator of the transfer of these signals through differential expression of key placental genes. We used microarrays to examine placental gene expression responses to maternal protein deficiency (6% vs. 24% protein) and Heligmosomoides bakeri infection.
Publication Title
Expression of growth-related genes in the mouse placenta is influenced by interactions between intestinal nematode (Heligmosomoides bakeri) infection and dietary protein deficiency.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 50 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Biomarkers of osteoarthritis (OA) that can accurately diagnose the disease at the earliest stage would significantly support efforts to develop treatments for prevention and early intervention. The different stages of disease progression are described by the complex pattern of transcriptional regulations. The dynamics in pattern alterations were monitored in each individual animal during the time-course of OA progression.
Publication Title
Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis.
Sample Metadata Fields
Treatment
View Samples