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GSE9010
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HOXB4 mediates expansion of adult and embryo-derived hematopoietic stem cells (HSCs) when expressed ectopically. To define the underlying molecular mechanisms, we performed gene expression profiling in combination with subsequent functional analysis using enriched adult HSCs expressing inducible HOXB4. A substantial number of the identified HOXB4 target genes are involved in signaling pathways important for controlling self-renewal, maintenance and differentiation of stem cells. Functional assays performed on selected pathways confirmed the biological coherence of the array results. HOXB4 activity protected adult HSCs from the detrimental effects mediated by the proinflammatory cytokine TNF-alpha. Furthermore, we demonstrate that HOXB4 activity and FGF-signaling are intertwined. HOXB4-mediated expansion of adult HSCs was enhanced by specific and complete inhibition of FGF-receptors. Based on our results we propose that HOXB4 governs pivotal cell-intrinsic pathways involved in the regulation of cell cycle, differentiation and apoptosis. Our results strongly suggest that HOXB4 modulates the response of HSCs to multiple extrinsic signals in a concerted manner, thereby shifting the balance towards stem cell self-renewal.
Publication Title
HOXB4's road map to stem cell expansion.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To unravel the molecular mechanism by which HOXB4 promotes the expansion of early hematopoietic progenitors within differentiating ES cells, we analzed the gene expression profiles of embryoid bodies (EBs) in which transcription of HOXB4 had been induced or not induced. A substantial number of the identified HOXB4 target genes are involved in signaling pathways important for controlling self-renewal, maintenance and differentiation of stem cells. Furthermore, we demonstrate that HOXB4 activity and FGF-signaling are intertwined. HOXB4-mediated expansion of ES cell-derived early progenitors was enhanced by specific and complete inhibition of FGF-receptors. In contrast, the expanding activity of HOXB4 on hematopoietic progenitors in day4-6 embryoid bodies was blunted in the presence of basic FGF (FGF2) indicating a dominant negative effect of FGF-signaling on the earliest hematopoietic cells. Taken together, we show that modulation of FGF signaling is an essential feature of HOXB4 activity in the context of embryonic hematopoiesis.
Publication Title
HOXB4's road map to stem cell expansion.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) facilitate breast cancer (BC) metastasis, however stable molecular changes that result as a consequence of these processes remain poorly defined. Therefore, we sought to identify molecular markers that could distinguish tumor cells that had completed the EMT:MET cycle in the hopes of identifying and targeting unique aspects of metastatic tumor outgrowth.Therefore, normal murine mammary gland (NMumG) cells transformed by overexpression of EGFR (NME) cells were cultured in the presence of TGF-beta1 (5 ng/ml) for 4 weeks, at which point TGF-beta1 supplementation was discontinued and the cells were allowed to recover for an additional 4 weeks (Post-TGF-Rec). Total RNA was prepared from unstimulated cells (Pre-TGF) of similar passage and compared by microarray analysis.
Publication Title
Fibroblast growth factor receptor splice variants are stable markers of oncogenic transforming growth factor β1 signaling in metastatic breast cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.
Publication Title
Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinsons disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. To gain a better understanding of the consequences of excessive SNCA expression on basal ganglia function, we performed transcriptome analysis of striatal tissue from male Thy1-aSyn-mice and wt littermates. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.
Publication Title
Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
There are no effective treatments or clinical response markers for systemic sclerosis (SSc). We sought to assess the potential of novel imaging biomarkers and gene expression profiling approaches in a clinical trial of the tyrosine kinase inhibitor dasatinib in SSc patients with interstitial lung disease (SSc-ILD).
Publication Title
Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Repro9 in an allele of Mybl1 (A-Myb) transcription factor obtained in ENU screen to identify alleles causing mouse infertility. Repro9/repro9 mutant males are infertile due to meiotic arrest at pachytene stage. Mutants show wide range of abnormalities including inefficient chromosome synapsis, sex body formation and progression through meiotic cycle. Females are unaffected. To determine genes transcriptionally regulated by MYBL1 we analyzed gene expression profiles of wild type and repro9/repro9 mutant testis at 14 and 17 days postpartum. Analysis revealed many misregulated genes, in majority downregulated, at day 14 pp and even more at day 17 pp, probably due to secondary effects of meiotic arrest. Significantly misregulated genes were characterized by Gene Ontology. Comparative gene expression analysis uncovered potential targets of MYBL1 regulation that play roles in regulation of transcription, cell cycle, apoptosis, protein phosphorylation and ubiquitination, chromosome organization and others.
Publication Title
A-MYB (MYBL1) transcription factor is a master regulator of male meiosis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression of mice bone marrow pre-B cells from both control and Vav-Cre Mef2cfl/fl mice (9 months old)
Publication Title
MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression of mice bone marrow pro-B cells from both control and Vav-Cre Mef2cfl/fl mice (9 months old)
Publication Title
MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.
Sample Metadata Fields
Age, Specimen part
View Samples