The study of the roles of macrophages in the microenvironment of cancer cells (tumor-associated macrophages, TAM) has gained deep insight over the recent years. Here, we describe gene expression profile of chronic lymphocytic leukemia (CLL)-associated macrophages, also called nurse-like cells (NLC), derived from in vitro co-cultures system.
Human monocyte recognition of adenosine-based cyclic dinucleotides unveils the A2a Gαs protein-coupled receptor tonic inhibition of mitochondrially induced cell death.
Specimen part, Disease, Disease stage
View SamplesExpression data from this experiment is part of a larger project aimed at defining the individual effects and synergistic effects of ROCK inhibitor Y-27632 and conditioned media from irradiated J2 cells when applied to epithelial cells. This data set consists of four individual samples, each of which are total RNA collected from human foreskin keratinocyte cells, either grown in F medium (control), treated with Y-27632, grown in conditioned medium (as described in associated publication), or both treatments.
Multifactorial analysis of conditional reprogramming of human keratinocytes.
Specimen part, Treatment
View SamplesOrigins of the brain tumor, medulloblastoma, from stem cells or restricted pro-genitor cells are unclear. To investigate this, we activated oncogenic Hedgehog signaling in multipotent and lineage-restricted CNS progenitors. We observed that normal unipo-tent cerebellar granule neuron precursors (CGNP) derive from hGFAP+ and Olig2+ rhombic lip progenitors. Hedgehog activation in a spectrum of early and late stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and that they retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hedgehog signaling promotes medulloblastoma from lineage-restricted granule cell progenitors.
Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma.
No sample metadata fields
View SamplesPrimary human hepatocytes (PHH) are a main instrument in drug metabolism research and in the prediction of drug-induced phase I/II enzyme induction in humans. The HepG2 liver-derived cell line is commonly used as a surrogate for human hepatocytes, but their use in ADME and toxicity studies can be limited because of lowered basal levels of metabolizing enzymes. Despite their widespread use, the transcriptome of HepG2 cells compared to PHH is not well characterized. In this study, microarray analysis was conducted to ascertain the differences and similarities in mRNA expression between HepG2 cells and human hepatocytes before and after exposure to a panel of fluoroquinolone compounds. Comparison of the nave HepG2 cell and PHH transcriptomes revealed a substantial number of basal gene expression differences. When HepG2 cells were dosed with a series of fluoroquinolones, trovafloxacin, which has been associated with human idiosyncratic hepatotoxicity, induced substantially more gene expression changes than the other quinolones, similar to previous observations with PHH. While TVX-treatment resulted in many gene expression differences between HepG2 cells and PHH, there were also a number of TVX-induced commonalities, including genes involved in RNA processing and mitochondrial function. Taken together, these results provide insight for interpretation of results from drug metabolism and toxicity studies conducted with HepG2 cells in lieu of PHH, and could provide further insight into the mechanistic evaluation of TVX-induced hepatotoxicity.
Trovafloxacin-induced gene expression changes in liver-derived in vitro systems: comparison of primary human hepatocytes to HepG2 cells.
Sex, Specimen part
View SamplesTo gain insights into tumor heterogeneity in anti-cancer drug responses of patient-derived xenograft models of HER2+ breast cancer brain metastases, we performed transcriptome gene expression profiling by Ion AmpliSeqâ„¢ Transcriptome sequencing that targets more than 20,000 human genes. Our data found that all anti-cancer drugs responders have significantly higher expression levels of AKT-mTOR-dependent signature genes as compared to the non-responders, suggesting that most HER2+ breast cancer brain metastases are depend on the AKT-mTOR pathway Overall design: Gene expression profiles of five PDX samples were generated by Ion AmpliSeq Transcriptome sequencing, in duplcate, using Ion torrent Proton machine.
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases.
Specimen part, Disease, Subject
View SamplesThe beta1-adrenergic receptor (beta1AR; ADRB1) polymorphism Arg 389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that beta1-Arg389 and beta1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wildtype and transgenic mice that expressed either human beta1-Arg389 and beta1-Gly389 receptors, or AC5 adenyl cyclase, sampling at an early age and stage, prior to the onset of pathologic features. We observed substantial overlap of dysregulated genes across all three transgenic heart models, consistent with a shared coupling to cAMP-dependent regulation of cardiac processes and adaptive responses. All three models up-regulated genes associated with RNA metabolism and translation, and down-regulated genes associated with mitochondria and energy metabolism, consistent with cAMP-driven increase in cardiac contractility, protein synthesis, and compensatory down-regulation of mitochondrial energy production. Both beta1AR transgenics activated additional genes associated with kinase-dependent pathways, and uniquely, beta1-Arg389 hearts caused up-regulation of genes associated with inflammation, programmed cell death, and extracellular matrix. These results substantially expand the scope of 7-transmembrane domain receptor signaling propagation beyond known cognate G-protein couplings. Moreover, they implicate alterations of a repertoire of processes evoked by a single amino acid variation in the cardiac beta1AR that might be exploited for genotype-specific heart failure diagnostics and therapeutics.
Differential coupling of Arg- and Gly389 polymorphic forms of the beta1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs.
No sample metadata fields
View SamplesThe expression levels of Arabidopsis thaliana (Col-0) genes in several developmental stages during the seed-to-seedling transition were measured by using high-density Affymetrix arrays (Aragene.st1.1).
A Predictive Coexpression Network Identifies Novel Genes Controlling the Seed-to-Seedling Phase Transition in Arabidopsis thaliana.
No sample metadata fields
View SamplesAngiogenesis in cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sex, Specimen part, Treatment
View SamplesAngiogenesis in collagen gel cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sex, Specimen part
View SamplesWe used microarrays to identify genes that are differentially expressed in the absence of miR-998 expression.
An intronic microRNA links Rb/E2F and EGFR signaling.
Specimen part
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