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Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
FOXO transcription factors control cellular formation of reactive oxygen species (ROS), which critically contribute to cell survival and cell death in neuroblastoma. Here, we report that C10orf10, also named Decidual Protein induced by Progesterone (DEPP), is a direct transcriptional target of FOXO3 in human neuroblastoma. As FOXO3-mediated apoptosis involves a biphasic ROS accumulation, we analyzed cellular ROS levels in DEPP-knockdown cells by live-cell imaging. Knockdown of DEPP prevented the primary and secondary ROS accumulation during FOXO3 activation and attenuates FOXO3-induced apoptosis, whereas its overexpression raises cellular ROS levels and sensitizes to cell death. In neuronal cells, cellular steady state ROS are mainly detoxified in peroxisomes by the enzyme CAT/catalase. As DEPP contains a peroxisomal-targeting-signal-type-2 (PTS2) sequence at its N-terminus that enables protein import into peroxisomes, we analyzed the effect of DEPP on peroxisomal function by measuring the catalase enzyme activity. Catalase activity was reduced by conditional DEPP overexpression and significantly increased in DEPP-knockdown cells. Using live cell imaging and fluorescent peroxisomal and mitochondrial probes we demonstrate that DEPP localizes to peroxisomes and mitochondria in neuroblastoma cells. The combined data indicate that DEPP reduces peroxisomal activity and thereby impairs the cellular ROS detoxification capacity and contributes to death sensitization.
Publication Title
C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 71 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comprehensive analysis of gene expression in hematopoietic stem and progenitor cells from young and old mice.
Publication Title
Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaHiSeq2000
Description
Gene fusions and chimeric transcripts occur frequently in cancers and in some cases drive the development of the disease. An accurate detection of these events is crucial for cancer research and in a long-term perspective could be applied for personalized therapy. RNA-seq technology has been established as an efficient approach to investigate transcriptomes and search for gene fusions and chimeric transcripts on a genome-wide scale. A number of computational methods for the detection of gene fusions from RNA-seq data have been developed. However, recent studies demonstrate differences between commonly used approaches in terms of specificity and sensitivity. Moreover their ability to detect gene fusions on the isoform level has not been studied carefully so far. Here we propose a novel computational approach called InFusion for fusion gene detection from deep RNA sequencing data. Validation of InFusion on simulated and on several public RNA-seq datasets demonstrated better detection accuracy compared to other tools. We also performed deep RNA sequencing of two well-established prostate cancer cell lines. Using these data we showed that InFusion is capable of discovering alternatively spliced gene fusion isoforms as well as chimeric transcripts that include non-exonic regions. In addition our method can detect anti-sense transcription in the fusions by incorporating strand specificity of the sequencing library. Overall design: Detection of fusion genes and chimeric transcripts from deep RNA-seq data
Publication Title
InFusion: Advancing Discovery of Fusion Genes and Chimeric Transcripts from Deep RNA-Sequencing Data.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution .
Publication Title
Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A characteristic feature of anaplastic large cell lymphoma (ALCL) is the significant reduction of the T-cell expression program despite its T-cell origin, a finding very similar to the loss of B-cell identity of classical Hodgkin lymphoma (cHL). Previously we demonstrated that epigenetic mechanisms are active in cHL to induce this peculiar phenotype. The results show that combined DNA demethylation and histone acetylation of T-cell lines induce an almost complete extinction of the T-cell phenotype, including the down-regulation of essential T-cell receptor signalling pathway genes such as CD3, LCK and ZAP70, as well as an up-regulation of ALCL-characteristic genes. In contrast, combined DNA demethylation and histone acetylation of ALCL cells is not able to reconstitute their T-cell phenotype. This clearly demonstrates that similar epigenetic mechanisms are active in ALCL and cHL which are responsible for the extinction of their cell type characteristic phenotype.
Publication Title
Histone acetylation and DNA demethylation of T cells result in an anaplastic large cell lymphoma-like phenotype.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Ion Torrent Proton
Description
Rationale - Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage specification factor FOXP3 is essential for Treg cells' ability to uphold immunological tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. Objective - To define the regulation and functions of the two major FOXP3 isoforms, FOXP3fl and FOXP3?2, as well as to establish whether their expression is associated with ischemic atherosclerotic disease. Methods and Results - Human primary T-cells were transduced with lentiviruses encoding distinct FOXP3 isoforms. The phenotype and function of these cells were analyzed by flow cytometry, in vitro suppression assays and RNA-sequencing. We also assessed the effect of activation on Treg cells isolated from healthy volunteers. Treg cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3?2. FOXP3?2 induced specific transcription of GARP, which functions by tethering the immunosuppressive cytokine TGF-ß to the cell membrane of activated Treg cells. RT-PCR was used to determine the impact of alternative splicing of FOXP3 in relation with atherosclerotic plaque stability in a cohort of over 150 patients that underwent carotid endarterectomy. Plaque instability was associated with a lower FOXP3?2 transcript usage, when comparing plaques from patients without symptoms and patients with occurrence of recent (<1 month) vascular symptoms including minor stoke, transient ischemic attack or amaurosis fugax. No difference was detected in total levels of FOXP3 mRNA between these two groups. Conclusions - These results suggest that activated Treg cells suppress the atherosclerotic disease process and that FOXP3?2 controls a transcriptional program that acts protectively in human atherosclerotic plaques. Overall design: In this experiment we have analyzed 3 groups of each 3 biological repliactes equalling 9 samples in total.
Publication Title
Alternative Splicing of <i>FOXP3</i> Controls Regulatory T Cell Effector Functions and Is Associated With Human Atherosclerotic Plaque Stability.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 101 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profiling using microarray has been limited to profiling of differentially expressed genes at comparison setting since probesets for different genes have different sensitivities. We overcome this limitation by using a very large number of varied microarray datasets as a common reference, so that statistical attributes of each probeset, such as dynamic range or a threshold between low and high expression can be reliably discovered through meta-analysis. This strategy is implemented in web-based platform named Gene Expression Commons (http://gexc.stanford.edu/ ) with datasets of 39 distinct highly purified mouse hematopoietic stem/progenitor/functional cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, any scientist can explore gene expression of any gene, search by expression pattern of interest, submit their own microarray datasets, and design their own working models.
Publication Title
Gene Expression Commons: an open platform for absolute gene expression profiling.
Sample Metadata Fields
Sex, Age
View Samples
GSE77078- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Prospectively isolated neonatal bone marrow stroma and endothelium
Publication Title
Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms.
Publication Title
PAX5 overexpression is not enough to reestablish the mature B-cell phenotype in classical Hodgkin lymphoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus, Homo sapiens
- 29 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparison of gene expression data from human and mouse breast cancers: identification of a conserved breast tumor gene set.
Sample Metadata Fields
No sample metadata fields
View Samples