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GSE57578
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DCD is a gene amplified and overexpressed in a subset of breast tumors acting as a growth and survival factor. Patients with DCD-positive breast cancer have worse prognostic features. To investigate the role of DCD in breast tumorigenesis, we analyzed the consequences of its downregulation in human breast cancer cell lines using three specific shRNA lentivirus vectors. Genes up- and down-regulated by DCD were identified using Affymetrix microarray and analyzed by MetaCore Platform. We found that loss of DCD expression led to reduced cell proliferation, resistance to apoptosis, and suppressed tumorigenesis in immunodeficient mice. Network analysis of gene expression data revealed perturbed ERBB signaling following DCD shRNA expression including changes in the expression of ERBB receptors and their ligands. These findings imply that DCD promotes breast tumorigenesis via modulating the activity of the ERBB signaling pathways. As ERBB signaling is also important for neural survival, HER2+ breast tumors may highjack DCDs neural survival-promoting functions to promote tumorigenesis.
Publication Title
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Development of T-cells provides a unique opportunity to study cell-fate determination due to the accessability and the well defined stages of development. In order to understand the genetic programs underlying fetal and adult Tcell fate specification we subjected highly purified fetal and adult T-cell progenitor populations to a genomewide transcriptional analysis. The aim was to identify molecular elements that govern T-cell fate specification as a whole but ultimately to isolate elements that were specific for a given population in a specific developmental window.
Publication Title
Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Cells with slow proliferation kinetics that retain the nuclear label over long time periods – the label-retaining cells (LRCs) – represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells. Overall design: Transcriptome comparison of label-retaining biliary epithelial cells and non-label-retaining biliary epithelial cells (cells with GFP expression were compared to the cells without GFP). Illumina HiSeq 2000 was used to analyze 8 RNA samples from 4 mice.
Publication Title
A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Design: Persistent latently infected CD4+ T cells represent a major obstacle to HIV eradication. Histone deacetylase inhibitors (HDACis) are a promising activation therapy in a shock and kill strategy. However, off-target effects of HDACis on host gene expression are poorly understood in primary cells of the immune system. We hypothesized that HDACi-modulated genes would be best identified with a dose response analysis. Methods: Resting primary CD4+ T cells were treated with increasing concentrations (0.34, 1, 3, or 10 M) of the HDACi, suberoylanilide hydroxamic acid (SAHA), for 24 hours and then subjected to microarray gene expression analysis. Genes with dose-correlated expression were identified with a likelihood ratio test using Isogene GX and a subset of these genes with a consistent trend of up or downregulation at each dose of SAHA were identified as dose-responsive. Histone modifications were characterized in promoter regions of the top 6 SAHA dose-responsive genes by RT-qPCR analysis of immunopreciptated chromatin (ChIP). Results: A large number of genes were shown to be up (N=657) or down (N=725) regulated by SAHA in a dose-responsive manner (FDR p-value < 0.05 and fold change |2|). Several of these genes (CTNNAL1, DPEP2, H1F0, IRGM, PHF15, and SELL) are potential in vivo biomarkers of SAHA activity. SAHA dose-responsive gene categories included transcription factors, HIV restriction factors, histone methyltransferases, and host proteins that interact with HIV proteins or the HIV LTR. Pathway analysis suggested net downregulation of T cell activation with increasing SAHA dose. Histone acetylation was not correlated with host expression, but plausible alternative mechanisms for SAHA-modulated expression were identified. Conclusions: Numerous host genes in CD4+ T cells are modulated by SAHA in a dose-responsive manner, including genes that may negatively influence HIV activation from latency. Our study suggests that SAHA influences gene expression through a confluence of several mechanisms, including histone acetylation, histone methylation, and altered expression and activity of transcription factors.
Publication Title
Dose-responsive gene expression in suberoylanilide hydroxamic acid-treated resting CD4+ T cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination
Publication Title
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either Phosphatase and tensin homolog (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signaling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around two weeks after the crush injury. Remarkably, we now find that simultaneous deletion of both PTEN and SOCS3 enable robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only result in the induction of many growth-related genes, but also allow RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as a key for sustaining long-distance axon regeneration in adult CNS, a crucial step toward functional recovery.
Publication Title
Sustained axon regeneration induced by co-deletion of PTEN and SOCS3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Antigen uptake, processing and presentation by dendritic cells are regulated by complex intra- and inter-cellular signalling events. Typical vaccine adjuvants lead to the transcription of pro-inflammatory cytokines and chemokines which relate to immune induction.
Publication Title
Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: The goal of this study is to identify host genes whose expression is perturbed in primary CD4+ T cells by histone deacetylase (HDAC) inhibitors (HDACi) SAHA and RMD, which have different potencies and specificities for various HDACs. The study aims to evaluate the effects of SAHA and RMD that may promote or inhibit reactivation of HIV provirus out of latency. Methods: Peripheral blood mononuclear cells were collected from 4 HIV-seronegative donors. CD4+ T cells were isolated and utilized to generate an in vitro model of latent HIV infection (model developed in the Spina laboratory and previously described in Spina et al., 2013). Mock-infected cells were cultured in parallel to evaluate effects of SAHA and RMD that may be dependent on the exposure of cells to virus. Following generation of the model, cells were treated with SAHA, RMD or their solvent dimethyl sulfoxide (DMSO) for 24 hours. Mock-infected cells were treated in parallel. The experiment had 4 biological replicates, 6 conditions for each, for a total of 24 samples. ERCC spikes (Thermo Fisher Scientific, Inc.) were added to cell lysates based on cell number in each sample (10 ul of 1:800 dilution per million cells). Mix 1 was used for DMSO- and mix 2 for SAHA- and RMD-treated cells. After all samples were collected, RNA was extracted and subjected to deep sequencing by Expression Analysis, Inc. Sequence reads that passed quality filters were mapped using Tophat (human genome) or Bowtie (ERCC spikes and HIV) and counted using HTSeq. ERCC spikes with the same concentration in mixes 1 and 2 were utilized to remove unwanted technical variation. Any human gene which did not achieve at least 1 count per million reads in at least 4 samples or any ERCC that did not achieve at least 5 reads in at least 4 samples was discarded. Differential gene expression analysis was performed using library EdgeR in Bioconductor R. National Center for Biotechnology Information (NCBI) HIV-1 Human Interaction Database was then searched for genes that have been implicated in controlling HIV latency. EdgeR output was used to extract expression information of the genes of interest from the NCBI database to identify genes implicated in HIV latency that were modulated by SAHA and RMD. The resulting lists were manually curated to verify relevance to HIV latency, using the Description column of the NCBI database, as well as available PubMed references. Results: Using a custom built data analysis pipeline, ~100 million reads per sample were mapped to the human genome (build hg38). After applying filtering criteria, 16058 human transcripts, 19 ERCC spikes transcripts, and HIV NL4-3 transcripts were identified with the Tophat/Bowtie and HTSeq workflow. Differential expression analysis was performed between SAHA or RMD-treated and DMSO-treated cells. In addition, differential modulation of gene expression by SAHA and RMD in the model of HIV latency and mock-infected cells was assessed using EdgeR. In mock-infected cells, SAHA upregulated 3,971 genes and downregulated 2,940 genes; RMD upregulated 5,068 genes and downregulated 4,050 genes. In the model of HIV latency, SAHA upregulated 3,498 genes and downregulated 2,904 genes; RMD upregulated 5,116 genes and downregulated 4,053 genes (FDR < 0.05). SAHA modulated 6, and RMD 11 genes differentially between mock-infected cells and the model of HIV latency. Following search of the NCBI HIV-1 Human Interaction Database, 27 genes upregulated and 29 downregulated in common between SAHA and RMD were found to be relevant to regulation of HIV latency; 31 were up- and 32 downregulated by RMD only; and 6 were up- and 2 were downregulated by SAHA only. Conclusions: This study demonstrates that SAHA and RMD, which have different potencies and specificities for HDACs, modulate a set of overlapping genes implicated in regulation of HIV latency. Some of these genes may be explored as additional host targets for improving the outcomes of “shock and kill” strategies. Overall design: Transcriptomic profiling of the in vitro model of HIV latency and mock-infected cells treated with SAHA, RMD or the solvent DMSO (N=4 donors) by deep sequencing at Expression Analysis, Inc.
Publication Title
Long non-coding RNAs and latent HIV - A search for novel targets for latency reversal.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation. Overall design: Total RNA was extracted from HeLa cells treated with control (CTRL), UBL5 (#57, #58, or #82), or SART1 siRNAs for 48 h and processed for RNA-Seq analysis
Publication Title
UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells.
Sample Metadata Fields
No sample metadata fields
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