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GSE90471
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
3 samples of R1, R2 and R3 bone marrow monocytes were compared from 3 biological replicates in 3 separate experiments.
Publication Title
The Heterogeneity of Ly6C<sup>hi</sup> Monocytes Controls Their Differentiation into iNOS<sup>+</sup> Macrophages or Monocyte-Derived Dendritic Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In addition to helper and regulatory potential, CD4+T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4+T cells following immunotherapy. CD4 transfer into lymphodepleted animals or regulatory T cell (Treg)depletion promoted GzmB expression by tumor-infiltrating CD4+which was prevented by IL-2 neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized bythe expression of the transcription factors T-bet and Blimp-1. Whilst T-bet ablation restrictedIFN-gproduction, lossof Blimp-1preventedGzmB expressionin response to IL-2, suggesting these are two independent programs required forpolyfunctionality of tumor-reactive CD4+T cells. The data underscores the role of Treg, IL-2 and Blimp-1 controlling the differentiation of cytotoxic T cells and offers a pathway to enhancement of anti-tumor activity through their manipulation.
Publication Title
Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4<sup>+</sup> T Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We have investigated the regulation of anchorage-independent growth (AIG) by basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) in JB6 mouse epidermal cells in the context of wound repair versus carcinogenesis responses. bFGF induces an unusually efficient but reversible AIG response, relative to TPA-induced AIG which is irreversible. Distinct global gene expression profiles are associated with anchorage-independent colonies arising from bFGF-stimulated JB6 cells, relative to colonies arising from fully tumorigenic JB6 cells (RT101), including genes exhibiting reciprocal regulation patterns. Thus, while TPA exposure results in commitment to an irreversible and tumorigenic AIG phenotype, the AIG response to bFGF is reversible with essentially complete restoration of normal cell cycle check point control following removal of bFGF from growth medium. These results are consistent with the physiological role of bFGF in promoting wound healing, and suggest that natural mechanisms exist to reverse transformative cellular phenotypes associated with carcinogenesis.
Publication Title
Cellular dichotomy between anchorage-independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Using a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Publication Title
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Publication Title
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina HiScanSQ
Description
Phenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs. Overall design: RNA-seq
Publication Title
AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue are important components of energy expenditure. An RNAseq-based analysis of the mouse BAT transcriptome led us to identify GPR120 as a gene induced by thermogenic activation. GPR120, a G protein-coupled receptor binding unsaturated long-chain fatty acids, is known to mediate some beneficial metabolic actions of polyunsaturated fatty acids. We show that pharmacological activation of GPR120 induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired browning in response to cold. n-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF-21) by brown and beige adipocytes and increases blood FGF21 levels. The effects of GPR120 activation are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 constitutes a novel pathway of brown fat activation and involves FGF21. Overall design: eight adult male C57BL6 mice were maintained at thermoneutral temperature (29C). After two weeks, a subset of four mice was placed at 4C environment temperature for 24h. RNAseq was performed on the BAT tissues of these 2 groups.
Publication Title
The kallikrein-kinin pathway as a mechanism for auto-control of brown adipose tissue activity.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Strategies to enhance islet b-cell survival and regeneration while refraining inflammation through manipulation of molecular targets would provide means to stably replenish the deteriorating functional b-cell mass detected in both Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM). Herein we report that over expression of the islet enriched transcription factor Pax4 refrains development of hyperglycemia in the RIP-B7.1 mouse model of T1DM through reduced insulitis, decreased b-cell apoptosis correlating with diminished DNA damage and increased proliferation. Transcriptomics revealed up regulation of genes involved in immunomodulation, cell cycle and ER homeostasis in islets over expressing Pax4 as compared to the T2DM-linked mutant variant Pax4R129W. Pax4 but not Pax4R129W protected islets from thapsigargin-mediated ER-stress apoptosis. Collectively, Pax4 is a critical signaling hub coordinating regulation of distinct molecular pathways resulting in improved b-cell fitness whereas Pax4R129W sensitizes to death under stress. More importantly we highlight potential common pharmacological targets for the treatment of DM.
Publication Title
PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 186 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 186 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Sample Metadata Fields
Subject, Time
View Samples