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GSE45837
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Growth factor independence genes (Gfi1 and Gfi1b) repress recombination activating genes (Rag) transcription in developing B lymphocytes. Because all blood lineages originate from hematopoietic stem cells (HSCs) and different lineage progenitors have been shown to share transcription factor networks prior to cell fate commitment, we hypothesized that GFI family proteins may also play a role in repressing Rag transcription or a global lymphoid transcriptional program in other blood lineages. We tested the level of Rag transcription in various blood cells when Gfi1 and Gfi1b were deleted, and observed an upregulation of Rag expression in plasmacytoid dendritic cells (pDCs). Using microarray analysis, we observed that Gfi1 and Gfi1b regulate a broad spectrum of cellular processes in pDCs, but not a lymphoid specific transcriptional program. This study establishes a role for Gfi1 and Gfi1b in Rag regulation in a non-B lineage cell type
Publication Title
Gfi1 and gfi1b repress rag transcription in plasmacytoid dendritic cells in vitro.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have conducted a screen for factors that downregulate expression of the genes encoding the V(D)J recombinase (RAG1 and RAG2) during B cell development. We have identified the transcription factor Gfi1B as being one of the proteins capable of decreasing RAG transcription when overexpressed in Ableson transormed ProB cell lines. We have yet to determine whether the overexpression of Gfi1B downregulates the RAGs directly, or whether it initiates a signalling programme that results in RAG downregulation. We hypothesize that by comparing global gene expression patterns in cells that overexpress Gfi1B and those that do not, we can distinguish between these possibilities and additionally gain insight into the broader genetic program that may be influenced by Gfi1B during hematopoiesis.
Publication Title
Gfi1b negatively regulates Rag expression directly and via the repression of FoxO1.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
We recently identified pathogenic KIF1Bb mutations in sympathetic nervous system malignancies that are defective in developmental apoptosis. Here we deleted KIF1Bb in the mouse sympathetic nervous system based on a cre recombination system driven by the dopamine beta hydroxylase (DBH) promoter. We observed impaired sympathetic nervous function and misexpression of genes required for sympathoadrenal lineage differentiation in KIF1Bb deficient sympathetic ganglia. Overall design: We analyzed superior cervical ganglia from post-natal day 1 mice. We compared ganglia from four wild-type control animals (KIF1Bb fl/fl) with ganglia from four animals with conditional knockout of KIF1Bb (KIF1Bb fl/fl : DBHcre +/-).
Publication Title
Neuroblast differentiation during development and in neuroblastoma requires KIF1Bβ-mediated transport of TRKA.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
During development neuronal progenitors compete for growth factors such as nerve growth factor NGF and require the prolyl hydroxylase EglN3 and the kinesin KIF1Bß for developmental apoptosis. Inherited KIF1Bß loss-of-function mutations in neuroblastomas and pheochromocytomas implicate KIF1Bß as a 1p36.2 tumor suppressor, however the mechanism of tumor suppression is unknown. We found that KIF1Bß interacts with the RNA helicase A (DHX9) resulting in DHX9 nuclear accumulation to regulate apoptosis. KIF1Bß-dependent DHX9 nuclear localization leads to transcription of the apoptotic target XIAP-associated factor 1. DHX9 is induced when NGF is limiting and required for apoptosis in cells deprived of NGF. Overall design: NB1 cells were transduced to incorporate shRNA against DHX9 or a scrambled control, and transfected with a KIF1Bß expression vector or control, then transfected cells were isolated and lysed after 48h.
Publication Title
RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Foxo1 is required for proper developmental progression due to distinct functions at different stages of B cell development, but specific gene targets in pro-B cells are not identified. We performed a microarray analysis in v-Abl transformed pro-B cells to compare the gene expression pattern between wildtype and Foxo1 knockout cells.
Publication Title
MK5 activates Rag transcription via Foxo1 in developing B cells.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Publication Title
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to detect the differences in gene-expression of the periontal ligament between patients with healthy periodontal ligament and patients with periodontitis
Publication Title
The pathology of bone tissue during peri-implantitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study we want to ascertain the differences and similarities of infected and inflammated peri implant tissue versus healthy peri implant tissue at the mRNA level.
Publication Title
The pathology of bone tissue during peri-implantitis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
WNT-induced secreted protein 1 (WISP1/CCN4), a member of the CCN protein family, acts as a downstream factor of the canonical WNT-signaling pathway. A dysregulated expression of WISP1 often reflects its oncogenic potential by inhibition of apoptosis, a necessary form of cell death that protect cell populations for transformation into malignant phenotypes. WISP1-signaling is also known to affect proliferation and differentiation of human mesenchymal stem cells (hMSCs), which are fundamental for the constitution and maintenance of the musculoskeletal system. Our study emphasizes the importance of WISP1-signaling for cell survival of primary human cells. Therefore, we established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. We were able to demonstrate the consequence of cell death immediately after WISP1 down-regulation took place. Bioinformatical analyses of subsequent performed microarrays from WISP1 down-regulated vs. control samples confirmed this observation. We uncovered several clusters of differential expressed genes important for cellular apoptosis induction and immuno-regulatory processes, thereby indicating TRAIL-induced and p53-mediated apoptosis as well as IFNbeta-signaling. Since all of them act as potent inhibitors for malignant cell growth, in vitro knowledge about the connection with WISP1-signaling could help to find new therapeutic approaches concerning cancerogenesis and tumor growth in musculoskeletal tissues.
Publication Title
WISP 1 is an important survival factor in human mesenchymal stromal cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Murine Genome U74A Array (mgu74a)
Description
This series represent several subgroups of experiments designed to investigate the role of basal immunoglobulin signaling in immature B cell development. The first subgroup of arrays (Ctrl Mhi, Cre Mhi, Cre Mlo) was done to identify the changes in gene expression in immature B cells as a consequence of inducible deletion of surface IgM expression via Cre-LoxP mediated excision of Ig heavy chain. The second subgroup of arrays (GFPneg, GFPpos, FxE Ctrl, FxE HA) was done to identify the changes in gene expression in immature B cells as a consequence of blockade of tyrosine kinase signaling with herbimycin A treatment. The third subgroup of arrays (FxD, FxE, B6 Mneg, HEL Mhi) was done to establish gene expression profiles of immature B, pre B and pro B cells as reference platforms for the other two subgroups. (Tze etal. Public Library of Science Biology, 2005)
Publication Title
Basal immunoglobulin signaling actively maintains developmental stage in immature B cells.
Sample Metadata Fields
No sample metadata fields
View Samples