Erg is an ETS family transcription factor frequently overexpressed in human leukemias and has been implicated as a key regulator of hematopoietic stem cells (HSCs). However how Erg controls normal hematopoiesis, particularly at the stem cell level, remains poorly understood. Using homologous recombination, we generated an Erg knockdown allele (Ergkd) in which Erg expression can be restored upon Cre-mediated excision of a Stopper cassette. In Ergkd/+ mice, ~40% reduction in Erg dosage perturbed both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors.
Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.
Specimen part
View SamplesEffect of injury and Pseudomonas aeruginosa inoculation in Drosophila melanogaster
Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
Sex, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients.
Specimen part, Cell line, Treatment
View SamplesChromosomal rearrangements involving ETS factors, ERG and ETV1, occur frequently in prostate cancer. We here examine human prostate cancer cells control VCaP and LNCaP cells with ERG- or ETV1-silenced VCaP or LNCaP cells, respectively, in hormone deprived and stimulated conditions.
ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients.
Specimen part, Cell line, Treatment
View SamplesChromosomal rearrangements involving ETS factors, ERG and ETV1, occur frequently in prostate cancer. We here examine human prostate non-tumorigenic RWPE-1 cells with ERG- or ETV1-expressing stable RWPE-1 cell.
ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients.
Specimen part, Cell line
View SamplesChromosomal rearrangements involving ETS factors, ERG and ETV1, occur frequently in prostate cancer. We here examine mouse prostate cells from WT mice with s with T-ETV1 mice, which contains express the truncated human ETV1 under the endogenous Tmprss2 promoter. ETV1 expression can be tracked by GFP expression.
ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients.
Specimen part
View SamplesBacterial infections cause exaserbations in COPD. Study conducted to asses the effect of Nemiralisib, a PI3Kdelta inhibitor, on S. pneumoniae infected mice
PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner.
Specimen part, Time
View SamplesTo study the effects of treatment with an inhaled PI3Kδ inhibitor during recovery from an exacerbation of Chronic Obstructive Pulmonary Disease (COPD) due to corrective effects on neutrophils that display dysregulated migration characteristics. We aimed to develop novel induced sputum endpoints to demonstrate changes in neutrophil phenotype and proof of mechanism of action in the lung.
Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.
Sex, Specimen part, Treatment, Subject
View SamplesSF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in MDS. We have performed a comprehensive analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in bone marrow CD34+ cells of a large group of 82 MDS patients. Splicing factor mutations in MDS result in different mechanistic alterations in splicing and largely affect different genes, but these converged in common dysregulated pathways and cellular processes, including RNA splicing, translation and mitochondrial dysfunction, indicating that these mutations operate through common mechanisms in MDS. Many of these dysregulated pathways and cellular processes can be linked to the known disease pathophysiology and to the phenotypes associated with splicing factor mutations in MDS, whilst several others have not been previously associated with MDS, such as sirtuin signalling. Overall design: RNA-sequencing was performed on bone marrow CD34+ hematopoeitic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls to identify differential splicing between samples with mutations in the splicing factor SF3B1, SRSF2 or U2AF1 comparative to samples from myelodysplactic syndrome patients without mutations in these splicing factors and healthy controls. Processed data for the CD34+ hematopoeitic stem and progenitor cells are available in the files: CPM_table.txt.gz, Count_table.txt.gz and TPM_table.txt.gz. RNA-sequencing was also performed on monocytic, granulocytic and erythroid precursors from the bone marrow of patients with myelodysplastic syndrome and healthy controls to identify aberrant splicing in samples with mutations in splicing factors SF3B1 and SRSF2 comparative from healthy controls. Processed data for the monocytic, granulocytic and erythroid precursors are available in the files: CPM_table_fractions.txt, Count_table_fractions.txt and TPM_table_fractions.txt.
Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.
Specimen part, Disease, Subject
View SamplesBoth spotted long oligonucleotide arrays (GPL1384) and Affymetrix GeneChip arrays (GPL96) were used to analyze gene expression in six human head and neck squamous cell carinoma samples versus control samples or lymph node metastases of the same patients. Hybridizations of HG-U133A GeneChip arrays were performed using standard Affymetrix protocols and equipment. Before hybridization on DKFZ Operon 27k long oligonucleotide arrays, 2 g RNA were amplified by one round of linear isothermal RNA amplification, followed by Cy-dUTP incorporation using Klenow fragment. Hybridizations were performed for 16 h at 42 C in a GeneTAC Hybridization Station (Genomic Solutions) using UltraHyb hybridization buffer (Ambion). Hybridized microarrays were scanned at 5 m resolution on a GenePix 4000B microarray scanner (Axon Instruments). Raw signal intensities from both platforms were normalized applying variance stabilization (W. Huber et al., Bioinformatics 18 Suppl 1, 2002). Expression ratios were compared for those genes represented in both array platforms.
Patient-based cross-platform comparison of oligonucleotide microarray expression profiles.
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