This SuperSeries is composed of the SubSeries listed below.
Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging.
Age, Specimen part
View SamplesCutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in the U.S. annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). In order to identify potential targets for molecularly targeted chemoprevention, we performed integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar UV-driven Hairless mouse model. We identified the major transcriptional drivers of this sequence showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this UV-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. Overall design: We sought to identify important genetic events that drive squamous cell carcinoma development through combined analysis of next generation sequencing of matched patient samples with a UV-driven mouse model to identify key pathways.
Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.
Specimen part, Subject
View SamplesGene expression profiling of the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminence, and cerebral cortex (CTX) at various embryonic stages (E12.5, E14 and E16).
Comprehensive spatiotemporal transcriptomic analyses of the ganglionic eminences demonstrate the uniqueness of its caudal subdivision.
Sex, Specimen part
View SamplesExpression in GFP vs. GFP/hTERT transduced CD8 T Lymphocytes from Healty Donors (HD) 1 and 2 at early and late passages. Using CD8+ T lymphocyte clones over-expressing telomerase we investigated the molecular mechanisms that regulate T cell proliferation. Transduction and subcloning procedures were performed on CD8 + naive T-cell clones isolated from two different healthy individuals aged between 30 to 35 years (HD1 and HD2). T-cell cloneswere transduced to express hTERT/GFP or GFP alone.
Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase.
No sample metadata fields
View SamplesUsing CD8+ T lymphocyte clones over-expressing telomerase weinvestigated the molecular mechanisms that regulate T cell proliferation. Transduction and subcloning procedures were performed on CD8 + naive T-cell clones isolated from two different healthy individuals aged between 30 to 35 years (HD1 and HD2). T-cell cloneswere transduced to express hTERT/GFP or GFP alone. HD2 was profiled on U133Plus 2.0 and submitted as a separate GEO series.
Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase.
No sample metadata fields
View SamplesUsing CD8+ T lymphocyte clones over-expressing telomerase weinvestigated the molecular mechanisms that regulate T cell proliferation. Transduction and subcloning procedures were performed on CD8 + naive T-cell clones isolated from two different healthy individuals aged between 30 to 35 years (HD1 and HD2). T-cell cloneswere transduced to express hTERT/GFP or GFP alone. HD1 was profiled on U133A and submitted as a separate GEO series.
Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.
Specimen part
View SamplesRNA polymerase III (pol III) synthesizes short non-coding RNAs, many of which, including tRNAs, Rpph1 RNA, Rn5s rRNA, and Rmrp RNA, are essential for translation. Accordingly, pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by mTORC1 kinase, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of pol III transcription activity is so far lacking. Here we document pol III occupancy of its target genes in mouse liver during the diurnal cycle and show that pol III occupancy rises before the onset of the night, stays high during the night, when mice normally ingest food and when translation is increased, and decreases in daytime. By comparing diurnal pol III occupancy in wild-type mice, arrhythmic mice owing to inactivation of the Arntl gene, mice fed at regular intervals during both night and day, and mice lacking the Maf1 gene, we show that whereas higher pol III occupancy during the night reflects a MAF1-dependent response to feeding, the rise of pol III occupancy before the onset of the night reflects a circadian clock-dependent response. Thus, pol III transcription during the diurnal cycle is regulated both in response to nutrients and by the circadian clock, which allows anticipatory pol III transcription.
Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.
Specimen part
View SamplesReexpression of microRNAs miR-15a/16-1 in a cell line deficient for these miRs (homozygous deletion of chromosomal region 13q14) results in the downregulation of certain mRNAs.
The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sex
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