This file contains gene microarray data from bone marrow pre-ul DC, in vitro derived CD103+CD11b+ and CD103+CD11b- cDC with or without retinoic acid.
Generation and transcriptional programming of intestinal dendritic cells: essential role of retinoic acid.
Sex, Specimen part
View SamplesThis file contains gene microarray data from subsets of human intestinal dendritic cells, as defined by their expression of CD103 and Sirpa. This will allow for better understanding of human intestinal DC subsets in general and will facilitate translation from findings in the mouse.
Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice.
Specimen part
View SamplesNaturally occurring CD25+CD4+ regulatory T cells (T reg cells) are currently intensively characterized because of their major importance in modulating host responses to tumors and infections, in preventing transplant rejection, and in inhibiting the development of autoimmunity and allergy. Originally, CD4+ T reg cells were identified exclusively by the constitutive expression of CD25, and many in vivo experiments have been performed using depleting antibodies directed against CD25. However, both the existence of CD25 T reg cells, especially within peripheral tissues, as well as the expression of CD25 on activated conventional T cells, which precludes discrimination between T reg cells and activated conventional T cells, limits the interpretation of data obtained by the use of anti-CD25 depleting antibodies. The most specific T reg cell marker currently known is the forkhead box transcription factor Foxp3, which has been shown to be expressed specifically in mouse CD4+ T reg cells and acts as a master switch in the regulation of their development and function. To address the question of the in vivo role of T reg cells in immunopathology, we have generated bacterial artificial chromosome (BAC)transgenic mice termed depletion of regulatory T cell (DEREG) mice, which express a diphtheria toxin receptor (DTR) enhanced GFP (eGFP) fusion protein under the control of the foxp3 locus, allowing both detection and inducible depletion of Foxp3+ T reg cells. The gene expression profile of both CD4+eGFP+FoxP3+ and CD4+eGFPnegFoxP3neg cells isolated from DEREG mice was here analyzed by micro array.
Immunostimulatory RNA blocks suppression by regulatory T cells.
Specimen part
View SamplesPlasmacytoid dendritic cells (pDC) efficiently produce large amounts of type I interferon in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDC) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. Here, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDC, but not cDC. We confirmed the constitutive expression of Dusp9 at the protein level in pDC generated in vitro by culture with Flt3L and ex vivo in sorted splenic pDC. Dusp9 expression was low in B220- bone marrow precursors and was up-regulated during pDC differentiation, concomitant with established pDC markers. Higher expression of Dusp9 in pDC correlated with impaired phosphorylation of the MAPK ERK1/2 upon TLR9 stimulation. Notably, Dusp9 was not expressed at detectable levels in human pDC, although these displayed similarly impaired activation of ERK1/2 MAPK compared to cDC. Enforced retroviral expression of Dusp9 in mouse GM-CSF-induced cDC increased the expression of TLR7/9-induced IL-12p40 and IFNwhereas IL-10 levels were diminished. Taken together, our results suggest that the species-specific, selective expression of Dusp9 in murine pDC contributes to the differential cytokine/interferon output of pDC and cDC.
Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
No sample metadata fields
View SamplesWe used next generation sequencing to analyze the gene expression changes in U2OS osteosarcoma cells expressing shRNA targeting the promyelocytic leukemia (PML) gene transcripts Overall design: cDNA libraries of U2OS cells expressing control shRNA or shRNA targeting PML were generated from one biological replicate
PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4.
No sample metadata fields
View SamplesTo determine if aberrant activation of endothelin-1 (Et1) could lead to the dysregulation of many downstream genes, we exposed fibroblasts to exogenous ET1 peptide and assayed for transcriptional changes by microarray. Mouse dermal fibroblasts were treated with exogenous Et1 peptide for 24 hours. ET1 treatment resulted in significant expression changes primarily downregulation of a number of genes. In particular, Tgf2 and Tgf3 were among the downregulated genes, which in turn alter the expression status of their many target genes. These data suggest that the stable silencing of Et1 is important for the phenotypic stability of dermal fibroblasts, and perhaps many other cell types as well.
Localized methylation in the key regulator gene endothelin-1 is associated with cell type-specific transcriptional silencing.
No sample metadata fields
View SamplesCertain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing. Overall design: RNA sequencing profiles from 87 GFP-positive GABAergic SNr neurons and 9 GFP-negative SNr cells were carried out. However only 80 samples that passed initial quality control and that were included in the data processing are represented in this record.
The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Specimen part, Cell line, Subject
View SamplesTh1 and Th2 cells arise from a common precursor cell in response to triggering through the TCR and cytokine receptors for IL-12 or IL-4. This leads to activation of complex signaling pathways, which are not known in detail. Disturbances in the balance between type 1 and type 2 responses can lead to certain immune-mediated diseases. Thus, it is important to understand how Th1 and Th2 cells are generated. To clarify the mechanisms as to how IL-12 and IL-4 induce Th1 and Th2 differentiation and how TGF-beta can inhibit this process, we have used oligonucleotide arrays to examine the early polarization of Th1 and Th2 cells in the presence and absence of TGF-beta after 0, 2, 6 and 48 hours of polarization.
Identification of novel genes regulated by IL-12, IL-4, or TGF-beta during the early polarization of CD4+ lymphocytes.
No sample metadata fields
View Samples17-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/d) ER-antagonist ICI182,780 (3 mg/kg/d). Untreated HPH rats and normoxic rats served as controls. Using a false discovery rate of 10%, we identified a significantly differentially regulated genome in E2-treated vs. untreated hypoxia rats. Genes most up-regulated by E2 encoded matrix metalloproteinase 8, S100 calcium binding protein A8, and IgA Fc receptor; genes most down-regulated by E2 encoded olfactory receptor 63, secreted frizzled-related protein 2, and thrombospondin 2. Several genes affected by E2 changed in the opposite direction after ICI182,780 co-treatment, indicating an ER-regulated genome in HPH lungs. The bone morphogenetic protein antagonist Grem1 (gremlin 1) was up-regulated by hypoxia, but found to be among the most down-regulated genes after E2 treatment. Gremlin 1 protein was reduced in E2-treated vs. untreated hypoxic animals, and ER-blockade abolished the inhibitory effect of E2 on Grem1 mRNA and protein. In conclusion, E2 ER-dependently regulates several genes involved in proliferative and inflammatory processes during hypoxia. Gremlin 1 is a novel target of the E2-ER axis in HPH. Understanding the mechanisms of E2 gene regulation in HPH may allow for selectively harnessing beneficial transcriptional activities of E2 for therapeutic purposes.
Estrogen receptor-dependent attenuation of hypoxia-induced changes in the lung genome of pulmonary hypertension rats.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A circadian gene expression atlas in mammals: implications for biology and medicine.
Specimen part
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