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SRP060598
Homo sapiens
6 Downloadable Samples
NextSeq500
Description
Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signalling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here we show that multinucleate OIS cells originated mostly from failed mitosis. Prior to senescence, mutant RasV12 activation in primary human fibroblasts compromised mitosis, associated with abnormal expression of mitotic genes that enter M-phase. Simultaneously, RasV12 activation enhanced survival of damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional up-regulation of Mcl1 was responsible for enhanced slippage of cells with mitotic defects and subsequent cell survival. Importantly, mitotic slippage and oncogene signalling synergistically induced senescence and key senescence regulators p21 and p16. We propose that activated Ras induces transcriptional changes that predispose cells undergoing OIS to mitotic stress and multinucleation. Overall design: We used RNA-seq of IMR90 cells with inducible expression of oncogenic RasV12 that were synchronised in mitosis, to characterise the nature of mitotic defects that lead to multinucleation of oncogene-induced senescent cells
Publication Title
Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
We examined the effects of TNFa and Spt5, the major DSIF subunit, on nascent and mature transcripts using RNA-Seq of chromatin-associated and cytoplasmic transcripts. Overall design: RNA was extracted from the cytosolic and chromatin fractions of control and Spt5 KD cells that were treated with TNFa for 1 hour
Publication Title
Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of -catenin in EGFR TKI resistance has been previously reported however the precise mechanism by which -catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of -catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call adaptive persisters. We previously reported that EGFR-TKI treatment rapidly activates Notch3, and here describe the physical association of Notch3 with -catenin, leading to increased stability and activation of -catenin. We demonstrate that the combination of EGFR-TKI and a -catenin inhibitor inhibits the development of these adaptive persisters, decreases tumor burden, improves recurrence free survival, and overall survival in xenograft models. These results supports combined EGFR-TKI and -catenin inhibition in patients with EGFR mutant lung cancer.
Publication Title
Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HEK293T cells were transfected with the Rbp1-amr or slow (R729H-amr) -amanitin resistant subunit of RNA Pol II and selected with -amanitin 24 hours after transfection for additional 24 hours. Total RNA was extracted and global changes in gene expression were determined using microarray chips.
Publication Title
Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of DNA methylation in the nucleus accumbens in incubation of cocaine craving.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Gene expression profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
Publication Title
Role of DNA methylation in the nucleus accumbens in incubation of cocaine craving.
Sample Metadata Fields
Sex, Specimen part
View Samples- Caenorhabditis elegans
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Transciptomic analysis of germline tumor cells to understand the role of autophagy and neuronal differentiation in lifespan extension. Overall design: Methods: Worms were grown on control L444 seeded plates or gld-1 RNAi seeded plates and subjected to RNA isolation and sequencing using standard Illumina protocols. Conclusions: Fasting of animals expressing tumors increases their lifespan two-fold through autophagy and modular changes in transcription as well as metabolism.
Publication Title
Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in C. elegans.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Butyrate induces Treg via HDACi activity
Publication Title
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina HiSeq 2000
Description
Thymic Treg cells, mature non-Treg CD4+ single positive thymocytes, peripheral (spleen) resting and activated Treg cells were sorted from Foxp3-gfp reporter (wid type, WT) mice or Foxp3 enhancer CNS3 knockout (KO, carrying the same GFP reporter) mice. Total RNA was extracted and used for RNA sequencing to assess gene expression profiles. Overall design: Two 6-8 week old littermates of male Foxp3-gfp and Foxp3?CNS3-gfp mice were used to sort Treg cells and conventional CD4+ T cells. Lymphocyte preparation and electronic sorting were performed at the same time. RNA extraction, SMART amplification, library preparation were conducted in parallel.
Publication Title
A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T-cell developmental stages, including CD34+ lin- cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays.
Publication Title
New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling.
Sample Metadata Fields
Specimen part
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