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 SamplesSignalling pathways regulate all major cellular events in health and disease, including asthma development and progression. Complexity of human intracellular signalization can be explored using novel systemic approaches that exploit whole-transcriptome analysis. Cap-analysis-of-gene-expression (CAGE) is a method of choice for generating transcriptome libraries, as it interrogates only terminally capped mRNAs that have the highest probability to be translated into protein. In this study we for the first time systematically profiled differentially activated Intracellular Signalling Pathways (ISPs) in cultured primary human airway smooth muscle (ASM) cells from asthmatic (n=8) and non-asthmatic (n=6) subjects in a high-throughput assay, highlighting asthma-specific co-regulatory patterns. CAGE-libraries from primary human ASM cells were subject to massive parallel next generation sequencing, and a comprehensive analysis of ISP activation was performed using a recently developed technique OncoFinder. Analysis of 270 ISPs led to discovery of multiple pathways clearly distinguishing asthmatic from normal cells. In particular, we found 146 (p<0.05) and 103 (p<0.01) signalling pathways differentially active in asthmatic vs non-asthmatic samples. We identified seven clusters of coherently acting pathways functionally related to the disease. Pathways down-regulated in asthma mostly represented cell death-promoting pathways, whereas the up-regulated ones were mainly involved in cell growth and proliferation, inflammatory response and some specific reactions, including smooth muscle contraction and hypoxia - related signalization. Most of interactions uncovered in this study were not previously associated with asthma, suggesting that these results may be pivotal to development of novel therapeutic strategies that specifically address the ISP signature linked with asthma pathophysiology. Overall design: Capped mRNA profiles of primary bronchial smooth muscle cells from 8 asthmatic and 6 healthy donors were generated by deep sequencing using Illumina HiSeq1500.
Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells.
No sample metadata fields
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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