F4/80+ macrophages treated with TGFb2 are potently tolerogenic. Our understanding of the molecular mechanisms mediating the development of these tolerogenic properties is incomplete.
FcγRI is required for TGFβ2-treated macrophage-induced tolerance.
Sex, Specimen part, Treatment
View SamplesWe synthesized the PAX8-NFE2L2 fusion transcript and cloned it into a lentiviral vector, and used this to overexpress it in the murine prostate adenocarcinoma cell line TRAMP-C1. Overall design: We used high coverage RNA sequencing (>30 million reads per sample) to compare the expression profiles of cells expressing the PAX8-NFE2L2 fusion transcript to cells transduced with an empty vector.
Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers.
Specimen part, Cell line, Subject
View SamplesWe used microarrays to investigate gene expression changes induced by the inhibition of RRAS2 expression using shRNA techniques to stably knockdown the endogenous transcripts of this GTPase in human MDA-MB-231-Luc cells.
Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease.
Cell line
View SamplesCutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment.
The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
Specimen part
View SamplesExpression analysis of genes potentially regulated by BMPRII and beta-catenin. BMPRII has been linked as a genetic factor to the disease pulmonary arterial hypertension.
Disruption of PPARγ/β-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival.
Specimen part
View SamplesSome of the functions and mechanisms of PPAR?-mediated regulation of vascular homeostasis have been revealed, the potential role of PPAR? in angiogenesis is obscure. In human ECs, PPAR?-deficiency was studied using siRNA strategy and RNA sequencing was utilized to reveal angiogenesis-associated targets for PPARg. Overall design: Our aim is to reveal the possible role of PPARy in angiogenesis.
Loss of PPARγ in endothelial cells leads to impaired angiogenesis.
No sample metadata fields
View SamplesDevelopmental transitions can be described in terms of morphology and individual genes expression patterns, but also in terms of global transcriptional and epigenetic changes. Most of the large-scale studies of such transitions, however, have only been possible in synchronized cell culture systems. Here we generate a cell type specific transcriptome of an adult stem-cell lineage in the Arabidopsis leaf using RNA sequencing and microarrays. RNA profiles of stomatal entry, commitment, and differentiating cells, as well as of mature stomata and the entire aerial epidermis give a comprehensive view of the developmental progression.
Transcriptome dynamics of the stomatal lineage: birth, amplification, and termination of a self-renewing population.
Specimen part
View SamplesDevelopmental transitions can be described in terms of morphology and individual genes expression patterns, but also in terms of global transcriptional and epigenetic changes. Most of the large-scale studies of such transitions, however, have only been possible in synchronized cell culture systems. Here we generate a cell type specific transcriptome of an adult stem-cell lineage in the Arabidopsis leaf using RNA sequencing and microarrays. RNA profiles of stomatal entry, commitment, and differentiating cells, as well as of mature stomata and the entire aerial epidermis give a comprehensive view of the developmental progression.
Transcriptome dynamics of the stomatal lineage: birth, amplification, and termination of a self-renewing population.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BET bromodomains mediate transcriptional pause release in heart failure.
Age, Specimen part, Treatment
View SamplesHeart failure (HF) is driven via interplay between master regulatory transcription factors and dynamic alterations in chromatin structure. While pathologic gene transactivation in this context is known to be associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation, the role of epigenetic reader proteins in cardiac biology is unknown. We therefore undertook a first study of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET-family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to activation of canonical master regulators and effectors that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers in cardiac biology and identifies BET co-activator proteins as therapeutic targets in HF.
BET bromodomains mediate transcriptional pause release in heart failure.
Specimen part
View Samples