Gene Expression Profiling of Murine Mammary Stem Cells and Differentiated Derivatives.
Purification and unique properties of mammary epithelial stem cells.
Sex
View SamplesCerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparuminfected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor B (NF-B) activation cascade. The proinflammatory NF-B pathway was central to the regulation of the P falciparummodulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparuminfected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.
Plasmodium falciparum-infected erythrocytes induce NF-kappaB regulated inflammatory pathways in human cerebral endothelium.
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View SamplesWe profiled human DLBCL tumor samples (FF and FFPE matched pairs) to identify the transcripts which are less prone to degradation in FFPE
CD40 pathway activation status predicts response to CD40 therapy in diffuse large B cell lymphoma.
Specimen part
View SamplesWe profiled human DLBCL patient samples to discover predictive biomarkers
CD40 pathway activation status predicts response to CD40 therapy in diffuse large B cell lymphoma.
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View SamplesGene expression patterns were assessed in normal human bronchial epithelial (NHBE) cells exposed to cigarette smoke from a reference cigarette (2R4F, University of Kentucky) and a typical American brand of "light" cigarettes ("Lights") in order to develop a better understanding of the genomic impact of tobacco exposure, which can ultimately define biomarkers that discriminate tobacco-related effects and outcomes in a clinical setting. NHBE cells were treated with whole cigarette smoke for 15 minutes and alterations to the transcriptome assessed at 2, 4, 8 and 24 hours post-exposure using high-density oligonucleotide microarrays.
Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells.
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View SamplesGene expression patterns were assessed in normal human bronchial epithelial (NHBE) cells exposed to cigarette smoke (CS) from a typical "full flavor" American brand of cigarettes in order to develop a better understanding of the genomic impact of tobacco exposure, which can ultimately define biomarkers that discriminate tobacco-related effects and outcomes in a clinical setting. NHBE cells were treated with CS for 15 minutes and alterations to the transcriptome assessed at 1,2,4 and 24 hours post-CS-exposure using high-density oligonucleotide microarrays.
Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells.
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View SamplesLangerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells, myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC.
Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells.
Specimen part
View SamplesThe discovery of significant heterogeneity in the self-renewal durability of adult haematopoietic stem cells (HSCs) has challenged our understanding of the molecules involved in population maintenance throughout life. Gene expression studies in bulk populations are difficult to interpret since multiple HSC subtypes are present and HSC purity is typically less than 50% of the input cell population. Numerous groups have therefore turned to studying gene expression profiles of single HSCs, but again these studies are limited by the purity of the input fraction and an inability to directly ascribe a molecular program to a durable self-renewing HSC. Here we combine single cell functional assays with flow cytometric index sorting and single cell gene expression assays to gain the first insight into the gene expression program of HSCs that possess durable self-renewal. This approach can be used in other stem cell systems and sets the stage for linking key molecules with defined cellular functions. Overall design: single-cell RNA-Seq of haematopoietic stem cells
Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations.
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View SamplesMethods for identifying protein-protein interactions have mostly been limited to tagged exogenous expression approaches. We now establish a rapid, robust and comprehensive method for finding interacting proteins using endogenous proteins from limited cell numbers. We apply this approach called Rapid IP-Mass Spectrometry of Endogenous proteins (RIME) to identify ER, FoxA1 and E2F4 interacting proteins in breast cancer cells. From small numbers of starting cells, we find a comprehensive collection of known ER, FoxA1 and E2F4 targets, plus a number of novel unexpected interactors. One of the most ER (and FoxA1) associated interactors is GREB1, an estrogen induced gene with almost no known function. We apply RIME, in parallel with ER ChIP-seq, to identify ER protein interactors and ER binding events from solid tumor xenografts, resulting in the validation of the ER-GREB1 interactions. Furthermore, we establish a method for identifying endogenous interacting proteins from solid primary breast cancer samples, whih we apply to validate ER interactions with GREB1 and additional co-factors. Mechanistically, we show that GREB1 is recruited with ER to the chromatin where it functions as an essential estrogen-mediated regulatory factor required for effective ER transcriptional activity. Our novel approach enables, for the first time, the ability for discovery and validation of protein-protein interactions in whole tissue and solid tumors, revealing significant insight into ER regulatory factors.
Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor.
Cell line, Treatment
View SamplesExploring effect of progesterone/progestin treatment on gene expression Overall design: Two cell lines, three conditions (Full Media with E2, E2+ Progesterone, Full Media + R5020 Progestin)
Progesterone receptor modulates ERα action in breast cancer.
No sample metadata fields
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