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SRP043493
Mus musculus
20 Downloadable Samples
Illumina HiSeq 2000
Description
We used Fancd2-/- mice to understand its mechanism of action. Transcriptome analysis of cKit+ Sca1+ Lin- (KSL) cells discovered that only four genes changed their expression levels significantly after chronic OXM administration in both Fancd2-/- and wild-type mice: mKi67 and Cenpf were up-regualted by 1.4 fold; Spp1 and Oasl2 were significantly down-regulated by 10.5 and 1.5 fold, respectively. Both mKi67 and Cenpf genes are cell cycle-regulated genes and proliferation markers. Their up-regulation was consistent with our observation in flow cytometry analysis that oxymetholone stimulated the proliferation of hematopoietic stem and progenitor cells. RNAseq analysis showed no effects on mTert mRNA expression with chronic androgen therapy, but instead suggested down-regulation of Spp1 and Oasl2 as an important mechanism for the drug’s action. Our RNAseq analysis also revealed that Fancd2-/- KSL cells showed clear changes in mRNA expression profiles compared to wild-type controls: 430 genes were down-regulated by more than 1.5 fold, whereas 159 genes were up-regulated. Gene ontology analysis revealed key pathways to be significantly altered in Fancd2-/- KSL cells. Besides the abnormal cell cycle status expected from our earlier flow cytometry analysis, surprisingly we noticed that a group of genes involved in immune responses and inflammation, comprising Cfp (Properdin), Socs2, Ccr1, Ccr2, Ccr5, Chga (Chromogranin A), Ifi30 (Interferon Gamma-Inducible Protein 30), Lgmn, Txn, and Sell (selectin L), were up-regulated in Fancd2-/- KSL cells. We therefore hypothesize that some genes up-regulated in FA HSPCs may be part of an innate immune response to DNA damage. In addition, whole bone marrow cells were also analyzed in parallel with KSL cells. As compared to whole bone marrow cells, the genes enriched in KSL cells in wild-type mice were listed in details in the corresponding publication. This information can be a good resource for the future gene expression analysis of HSPCs. Finally, we compared the gene expression profiles of early progenitors between OXM-treated and placebo-treated mice. There were no significant differences at all in gene expression between OXM-treated wild-type erythroid progenitors and their placebo-treated wild-type counterparts, with no genes displaying an expression change higher than 1.2 fold. Importantly, no up-regulation of EPO-inducible genes such as Socs1, Socs2, Socs3, and Cish was seen in wild-type mice treated with OXM. Furthermore, there was no differential expression of the well-known EPO target transferrin receptor or any other major players of the Epo-R signaling network such as Bcl2l1, Cdc25a, Btg3, Ccnd2, Lyl1, Pim3, and Tnfrsf13c. These results indicate that EPO might not play a role in the action of OXM in the erythroid lineage. Overall design: The goal of this study is to investigate gene expression changes in Fancd2 knockout mice in response to oxymetholone treatment. The study focuses on two bone marrow cell populations: cKit+ Sca1+ Lin- cells (representing hematopoietic stem and progenitor cells) and Ter119+/CD71high/FSChigh cells (representing proerythroblasts and basophilic erythroblasts). Both populations were sorted twice by FACS to ensure the purity. Cells of interest were collected in Trizol and RNA was isolated using RNAeasy mini prep kit. mRNAs were positively selected using oligo(dT)- Dynobeads and treated with DNase I. RNAseq libraries were then constructed using Illumina TruSeq RNA Sample Prep Kit and sequenced as 51 base-length reads on an Illumina HiSeq 2000 genome analyzer. For KSL libraries, each sample represented total mRNA isolated from pooled KSL cells of 5 individual mice; for basophilic erythroblast libraries, each library represented total mRNA isolated from basophilic erythroblasts of one individual mouse; for whole bone marrow libraries, each sample represented a combined library originally from 5 individual mice. All reads were mapped to the mouse reference genome (version mm9) using Bowtie short read aligner software (http://bowtie-bio.sf.net). Most of the data analysis was performed using EdgeR GLM algorithms. For the comparison of oxymetholone KSL libraries vs placebo KSL libraries, more stringent pair-wise comparisons were used to keep a consistent flow cytometric setting among each pair. The common gene list was the one shared by all three comparisons: COM17 vs HSC_101b, HSC_13 vs HSC_18, and HSC_23 vs QZ_35 for Fancd2-/- KSL cells; HSC_3 vs QZ_36, HSC_22 vs HSC_24, and COM15 vs COM16 for wild-type KSL cells. Data-mining and pathway analysis were carried out with the MetaCore integrated software suite (Thomson Reuters, New York, USA).
Publication Title
Oxymetholone therapy of fanconi anemia suppresses osteopontin transcription and induces hematopoietic stem cell cycling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Fanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha.
Publication Title
TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
An RNA-seq study of altered gene expression and mutations in Ara-C resistant acute myeloid leukemia murine cell lines. The analysis of the RNA-seq data led to the identification of a large deletion within the Dck coding sequence of the B117H cell line, which produced an alternatively processed form of Dck mRNA. The RNA-seq analysis also identified the presence of an insertion mutation in Dck in the B140H cell line. The RNA-seq analysis also identified a number of significant expression changes which did not appear in a previous microarray analysis (GSE18322), as well as identified other mutations which may be contributing to Ara-C resistance. Overall design: Two highly Ara-C resistant cell lines, B117H and B140H were derived from Ara-C sensitive parental cell lines, B117P and B140P. Variations in gene expression as well identification of acquired mutations between these Ara-C resistant/sensitive sets were studied using various RNA-seq analysis tools.
Publication Title
Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in acute myeloid leukemia.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 3000
Description
Activated T cells differentiate into functional subsets which require distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to provide substrate for the tricarboxylic acid cycle and epigenetic reactions and here we identify a key role for GLS in T cell activation and specification. Though GLS-deficiency diminished T cell activation, proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet and Interferon-? expression and CD4 Th1 and CD8 CTL effector cell differentiation. These changes were mediated by differentially altered gene expression and chromatin accessibility, leading to increased sensitivity of Th1 cells to IL-2 mediated mTORC1 signaling. In vivo, GLS-null T cells failed to drive a Th17-mediated Graft-vs-Host Disease model. Transient inhibition of GLS, however, increased Th1 and CTL T cell numbers in viral and chimeric antigen receptor models. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation. Overall design: Cells were treated with glutaminase1 inhibitor or vehicle
Publication Title
Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Gene expression data from VHL teratomas comparing genes differentially expressed based on apoptotic response to tumor microenvironment.
Publication Title
Pleiotropic effects of the trichloroethylene-associated P81S VHL mutation on metabolism, apoptosis, and ATM-mediated DNA damage response.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide mRNA expression profiling was performed in AGS, gastric cancer cell line, upon miR-25 silencing. At 48 hours upon anti-miR-25-3p (miRNA inhibitor) and non-targeting control RNA transfection, the whole transcriptome profiling was performed in triplicates. The miR-25 silencing elevates the diffuse gastric cancer features like expression of COL1A2, expression of COL1A2 co-expressed genes, Epithelial to Mesenchymal Transition (EMT) and angiogenesis associated genes.
Publication Title
Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
SV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used MEFs expressing TAg or infected by SV40. Our analysis indicates that TAg can induce interferon-stimulated genes in MEFs and that this induction depends upon the LXCXE motif and p53 binding.
Publication Title
Induction of interferon-stimulated genes by Simian virus 40 T antigens.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
consequences of astrocytes on GSCs, gene expression profiles generated from glioblastoma stem-like cells grown alone (mono-culture) and compared to those generated 48h after the initiation of co-culture with astrocytes
Publication Title
Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The zinc finger transcription factor growth-factor-independent-1 (Gfi1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. Here, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B-cells show a hyperproliferative phenotype, leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and immunoglobulin deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell-cycle control elements may contribute to B-cell dependent autoimmunity. Gfi1 thus emerges as a novel master-regulator restricting autoimmunity.
Publication Title
Transcription factor Gfi1 restricts B cell-mediated autoimmunity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 175 Downloadable Samples
- Illumina HiSeq 2000
Description
Trascriptome analysis of osteosarcoma samples were performed Overall design: Tumor samples were obtained from a previously published Sleeping Beauty forward genetic screen, cell lines were derived from previous primary tumors and sequenced using Illumina HiSeq 2000
Publication Title
Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples