Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways exist that limit the prevalence of such cells? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to replication stress, generating further genomic instability, increased karyotype complexity, and ultimately cell cycle arrest. Cells with complex karyotypes exhibit features of senescence and a pro-inflammatory response that promotes their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that might well be a source of cancer cell immunosurveillance that must be overcome during malignant transformation. Overall design: Assay the transcriptional impact of aneuploidy by comparing the transcriptomes Euploid control RPE-1 cells in Aneuploid cycling RPE-1 cells and Aneuploid arrested RPE-1 cells using RNA-Seq.
Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.
Cell line, Treatment, Subject
View SamplesWe used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0).
Genomic evolution of the placenta using co-option and duplication and divergence.
Specimen part
View SamplesWe used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0). For these samples, at each stage the fetal placenta and maternal decidual tissues were dissected and profiled separately (See series 1).
Genomic evolution of the placenta using co-option and duplication and divergence.
Specimen part
View SamplesDCA (3,5-Dichloroanthranilic acid) is a newly identified synthetic defense elicitor. To perform a comparative analysis of defense responses triggered by DCA and the structurally related defense inducer INA (2,6-Dichloroisonicotinic acid) Affymetrix chip experiments were performed with Arabidopsis thaliana seedlings treated with one of these two compounds.
The synthetic elicitor 3,5-dichloroanthranilic acid induces NPR1-dependent and NPR1-independent mechanisms of disease resistance in Arabidopsis.
No sample metadata fields
View SamplesWe characterzised global changes in gene expresseion between 8 cell embryos and blastocysts to identify potential genes required for blastocyst formation.
Transcription factor AP-2γ is a core regulator of tight junction biogenesis and cavity formation during mouse early embryogenesis.
Specimen part
View SamplesActivating mutations of FGFR3 are found in a high proportion of bladder tumours. The molecular consequences of FGFR3 mutation in urothelial cells and the mechanisms by which mutant FGFR3 may drive bladder tumourigenesis are largely unknown.
Alteration of cell-cell and cell-matrix adhesion in urothelial cells: an oncogenic mechanism for mutant FGFR3.
Specimen part
View SamplesHuman cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-gamma and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-gamma-responsive promoters. However, neither synthesis nor secretion of IFN-gamma or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity.
Human cytomegalovirus IE1 protein elicits a type II interferon-like host cell response that depends on activated STAT1 but not interferon-γ.
Specimen part, Cell line
View SamplesSheep scrapie (Sc) is the classical transmissible spongiform encephalopathy (prion disease). The conversion of normal cellular prion protein (PrPC) to disease-associated prion protein (PrPSc) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion diseases and the impact of PrPSc accumulation on cellular biology are not fully understood. To define the molecular changes associated with PrPSc accumulation, primary sheep microglia were inoculated with PrPSc and then the transcriptional profile of these PrPSc-accumulating microglial cells was compared to the profile of PrPSc-lacking microglial cells using the Affymetrix Bovine Genome Array. The experimental design included three biological replicates, each with three technical replicates, and samples that were collected at the point of maximal PrPSc accumulation levels as measured by ELISA. The array analysis revealed 19 upregulated genes and 30 downregulated genes in PrPSc-accumulating microglia. Three transcripts (CCL2, SGK1, and AASDHPPT) were differentially regulated in a direction similar to previous reports from mouse or human models, whereas the response of three other transcripts (MT1E, NR4A1, PKP2) conflicted with previous reports. Overall, the results demonstrated a limited transcriptional response to PrPSc accumulation, when compared to microglia and macrophage cultures infected with other agents such as viruses and bacteria. This is the first microarray-based analysis of prion accumulation in primary cells derived from a natural TSE-host.
Limited transcriptional response of ovine microglia to prion accumulation.
No sample metadata fields
View SamplesTotal gene expression analysis was performed on RNA from testes extracted from two litters of constitutive homozygous and heterozygous H3f3b knockout mice compared to WT littermates.
Histone H3.3 regulates dynamic chromatin states during spermatogenesis.
Specimen part
View SamplesSummary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or desease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function.
Gene profiling in spinal cord injury shows role of cell cycle in neuronal death.
No sample metadata fields
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