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GSE70345
Homo sapiens
47 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes from patients with multiple myeloma, smoldering myeloma or monoclonal gammopathy of undetermined significance. We analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14+ monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis. The number of bone marrow CD14+CD16+ cells was higher in patients with active myeloma than in those with smoldering myeloma or monoclonal gammopathy of undetermined significance. Interestingly, sorted bone marrow CD14+CD16+ cells from myeloma patients were more pro-osteoclastogenic than CD14+CD16-cells in cultures ex vivo Moreover, transcriptional analysis demonstrated that bone marrow CD14+ cells from patients with multiple myeloma (but neither monoclonal gammopathy of undetermined significance nor smoldering myeloma) significantly upregulated genes involved in osteoclast formation, including IL21RIL21R mRNA over-expression by bone marrow CD14+ cells was independent of the presence of interleukin-21. Consistently, interleukin-21 production by T cells as well as levels of interleukin-21 in the bone marrow were not significantly different among monoclonal gammopathies. Thereafter, we showed that IL21R over-expression in CD14+ cells increased osteoclast formation. Consistently, interleukin-21 receptor signaling inhibition by Janex 1 suppressed osteoclast differentiation from bone marrow CD14+ cells of myeloma patients. Our results indicate that bone marrow monocytes from multiple myeloma patients show distinct features compared to those from patients with indolent monoclonal gammopathies, supporting the role of IL21R over-expression by bone marrow CD14+ cells in enhanced osteoclast formation.
Publication Title
<i>IL21R</i> expressing CD14<sup>+</sup>CD16<sup>+</sup> monocytes expand in multiple myeloma patients leading to increased osteoclasts.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung, and bladder cancers, and cardiovascular disease. The mechanisms behind arsenic's effects remain unclear, but recent research indicates that aresnic acts along sex-specific lines and may be an endocrine disruptor. The objective of this study was to evaluate the nature of gene expression chagnes among males and females exposed to arsenic contaminated water in Bangladesh at high and low dose exposures.The median wAs concentration for the low exposure group was 103 g/L for males and 117 g/L for females (range 50200 g/L). For the high exposure group, the median wAs concentration was 355 g /L for males (range 250-500 g /L) and 434 g/L for females (range 2321000 g /L). The PBMCs of males with high exposure compared to those with low exposure there were 534 differentially expressed genes (p <0.05); and for females with high exposure relative to low exposure there were 645 differentially expressed genes (p <0.05) in PBMCs of females.
Publication Title
Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression. Overall design: Three biological replicates of RNA-seq from cells expressing shRNA directed against macroH2A1 or luciferase as a control
Publication Title
MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 232 Downloadable Samples
- Illumina HiSeq 2500
Description
We performed Fluidigm C1 single cell sequencing analysis of wild-type and microRNA deficient (Dgcr8 knockout) mouse embryonic stem cells mock treated or transfected with either miR-294 or let-7. Overall design: Wild-type and Dgcr8 knockout cells grown in naïve culture conditions were mock transfected or transfected with miRNA mimics for let-7b or miR-294, single cells were captured on Fluidigm C1 24 hours post-transfection and then prepared for sequencing on Illumina HiSeq1000 following manufacturer''s protocol.
Publication Title
The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In vitro experiment of stimulation of monocyte-derived dendritic cells with Saccaromyces cerevisiae in exponential growth phase. This experiment was performed to verify the comparability of microarray
Publication Title
Using pathway signatures as means of identifying similarities among microarray experiments.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Affymetrix expression arrays were used to compare expression patterns upon knockdown of PARP-1, PARG, SIRT1, or macroH2A in comparison to Luciferase control.
Publication Title
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) are enzymes that modify target proteins in the nucleus by the addition and removal, respectively, of ADP-ribose polymers. Although a role for PARP-1 in gene regulation has been well established, the role of PARG is less clear. To investigate how PARP-1 and PARG coordinately regulate global patterns of gene expression, we used short hairpin RNAs (shRNAs) to stably knockdown PARP-1 or PARG in MCF-7 cells, followed by expression microarray analyses.
Publication Title
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic. We showed that glioma cells are able to progress towards a high-grade phenotype even in immunodeficient mice, albeit more slowly and this progression invariably requires a downregulation of immunostimulatory genes.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples