Neutrophil lysis after phagocytosis is a process potentially important in the pathogenesis of community-associated methicillin-resistant S. aureus (CA-MRSA) infection. The mechanism for this process is not currently known. Therefore, to better understand CA-MRSA virulence we used human oligonucleotide microarrays to investigate the mechanism underlying enhanced PMN lysis that occurs after phagocytosis of CA-MRSA.
Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus.
Specimen part, Treatment
View SamplesThe emergence of multidrug resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, resistant to the frontline anti-tubercular drugs rifampicin and isoniazid, forces treatment with less effective and toxic second-line drugs and stands to derail TB control efforts. However, the immune response to MDR Mtb infection remains poorly understood. Here, we determined the RNA transcriptional profile of in vitro generated macrophages to infection with either drug susceptible Mtb HN878 or MDR Mtb W_7642 infection. Overall design: Bone marrow-derived macrophages (BMDMs) from WT and Il1r1–/– mice were derived in 7 days in GM-CSF supplemented complete DMEM. Cells were infected with either Mtb HN878 or Mtb W_7642 (multiplicity of infection = 1) and RNA samples collected after 6 days.
Mycobacterium tuberculosis carrying a rifampicin drug resistance mutation reprograms macrophage metabolism through cell wall lipid changes.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.
Specimen part
View SamplesExpression response after induction of putative phrenic neuronal determinants in ES cell-derived motor neurons was compared to a pre-determined list of genes over-expressed in FACS-sorted primary.
Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.
Specimen part
View SamplesExpression response after induction of putative phrenic neuronal determinants in ES cells was compared to a pre-determined list of genes over-expressed in FACS-sorted phrenic cells.
Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.
Specimen part
View SamplesIPH-926 is an anticancer drug-resistant tumor cell line derived from a chemo-refractory human infiltrating lobular breast cancer (ILBC). IPH-926 ILBC cells were subjected to gene expression profiling using an Affymetrix HG U133 Plus 2.0 array.
ABCB1/MDR1 contributes to the anticancer drug-resistant phenotype of IPH-926 human lobular breast cancer cells.
Specimen part, Cell line
View SamplesHuman solid tumors contain rare cancer side population (SP) cells, which expel the fluorescencent dye H33342 and display cancer stem cell characteristics. Transcriptional profiling of cancer SP cells isolated by H33342 fluorescence analysis is a newly emerging approach to discover cancer stem cell markers and aberrant differentiation pathways. Using Affymetrix expression microarrays this study investigated differential gene expression between SP and non-SP (NSP) cells isolated from the CAL-51 human mammary carcinoma cell line.
Down-regulation of the fetal stem cell factor SOX17 by H33342: a mechanism responsible for differential gene expression in breast cancer side population cells.
Specimen part
View SamplesEffects of aneuploidy on gene expression in Arabidopsis thaliana containing extra copies of chromosome 5.
Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.
Specimen part, Subject
View SamplesAutosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation throughout the kidney parenchyma. It is caused by mutations in either of two genes, PKD1 and PKD2. Mice that lack functional Pkd1 (Pkd1null/null), develop rapidly progressive cystic disease during embryogenesis, and serve as a model to study human ADPKD. We examined the molecular pathways that modulate renal cyst growth in the Pkd1null/null model by performing global gene-expression proling in embryonic kidneys at day 14 and 17. Gene Ontology and gene set enrichment analysis were used to identify overrepresented signaling pathways in Pkd1null/null kidneys. We found dysregulation of developmental, metabolic, and signaling pathways (e.g. Wnt, calcium, TGF-b and MAPK) in Pkd1null/null kidneys.
Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease.
Specimen part
View SamplesThe molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional program which is subsequently reinforced by Zscan4c. Overall design: RNA sequencing of screen hits (3 biological replicates of GFP+ and GFP- sorted cells for each of 12 candidates).
Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.
Specimen part, Cell line, Subject
View Samples