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GSE8621
Mus musculus
8 Downloadable Samples
Description
Among the multiple mechanisms that control the intensity and duration of macrophage activation, the development of a state of refractoriness to a second stimulation in cells treated with LPS has long been recognized. Release of inhibitory cytokines and alterations in intracellular signaling pathways may be involved in the development of LPS tolerance. Although a number of molecules have been implicated, a detailed picture of the molecular changes in LPS tolerance is still missing. We have used a genome-wide gene expression analysis approach to (i) define which fraction of LPS target genes are subject to tolerance induction and (ii) identify genes that are expressed at high levels in tolerant macrophages. Our data show that in LPS tolerant macrophages the vast majority of LPS-induced gene expression is abrogated. The extent of tolerance induction varies for individual genes, and a small subset appears to be excepted. Compared to other negative control mechanisms of macrophages, e.g. IL-10-induced deactivation, LPS-tolerance inhibits a much wider range of transcriptional targets. Some previously described negative regulators of TLR-signaling (e.g. IRAK-M) were confirmed as expressed at higher levels in LPS-tolerant macrophages. In addition, we discuss other potential players in LPS tolerance identified in this group of genes.
Publication Title
A genome-wide analysis of LPS tolerance in macrophages.
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No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Plasmacytoid 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.
Publication Title
Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
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No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Two T7 based methods One round of Amplification (Affymetrix) and Two round of Amplification were compared to two Ribo-SPIA based systems, RiboSPIA and pico Ribo SPIA systems. Data for Pico-RiboSPIA are listed here.
Publication Title
Microarray-based comparison of three amplification methods for nanogram amounts of total RNA.
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No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
We have recently shown a remarkable regenerative capacity of the prenatal heart using a genetic model of mosaic mitochondrial dysfunction in mice. This model is based on inactivation of the X-linked gene encoding holocytochrome c synthase (Hccs) specifically in the developing heart. Loss of HCCS activity results in respiratory chain dysfunction, disturbed cardiomyocyte differentiation and reduced cell cycle activity. The Hccs gene is subjected to X chromosome inactivation, such that in females heterozygous for the heart conditional Hccs knockout approximately 50% of cardiac cells keep the defective X chromosome active and develop mitochondrial dysfunction while the other 50% remain healthy. During heart development, however, the contribution of HCCS deficient cells to the cardiac tissue decreases from 50% at midgestation to 10% at birth. This regeneration of the prenatal heart is mediated by increased proliferation of the healthy cardiac cell population, which compensate for the defective cells and allow the formation of a fully functional heart at birth. Here we performed microarray expression ananlyses on 13.5 dpc control and heterozygous Hccs knockout hearts to identify molecular mechanisms that drive embryonic heart regeneration.
Publication Title
Embryonic cardiomyocytes can orchestrate various cell protective mechanisms to survive mitochondrial stress.
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Sex, Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The purpose of this study was to analyze the genomic signatures and profiles of skin from ichthyosis (various subtypes) vs. healthy patients. The analysis strategy was to study differentially expressed genes common to the ichthyosis shared phenotype, as well as individual ichthyosis subtypes, and compare and contrast to the genomic profiles of atopic dermatitis and psoriasis.
Publication Title
Ichthyosis molecular fingerprinting shows profound T<sub>H</sub>17 skewing and a unique barrier genomic signature.
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Age, Specimen part, Disease
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Target genes of Fbxl10 during 3T3-L1 adipogenesis was analyzed
Publication Title
The FBXL10/KDM2B scaffolding protein associates with novel polycomb repressive complex-1 to regulate adipogenesis.
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Cell line, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Human Immunodeficiency Virus (HIV) associated nephropathy (HIVAN) is characterized clinically by both nephrosis and by rapidly progressive kidney dysfunction. HIVAN is characterized histologically by both collapsing focal segmental glomerulosclerosis and prominent tubular damage. Neutrophil Gelatinase Associated Lipocalin (NGAL) is known to be rapidly expressed in distal segments of the nephron at the onset of different types of acute kidney injury, but few studies have examined NGAL in chronic kidney disease models. We found that urinary NGAL (uNGAL) was highly expressed by patients with biopsy proven HIVAN, whereas HIV+ patients without HIVAN demonstrated lower levels. uNGAL was also highly expressed in the TgFVB mouse model of HIVAN, which demonstrated NGAL gene expression in dilated, microcystic segments of the nephron. These data show that NGAL is markedly upregulated in the setting of HIVAN, and suggest that uNGAL levels may provide a non-invasive screening test to detect HIVAN related tubular disease.
Publication Title
Urinary NGAL marks cystic disease in HIV-associated nephropathy.
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No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The perinatal period and early infancy are considered critical periods for lung development, and adversities during this period are believed to impact lung health in adulthood.The main factors affecting postnatal lung development and growth include environmental exposures, cigarette smoking, (viral) infections, allergic sensitization, and asthma.Therefore, we hypothesized that concomitant exposure in the early postnatal period in mice would cause more profound alterations in lung alveolarization and growth in adult life, quantified by stereology, and differently modulate lung inflammation and gene expression than either insult alone.Five-day-old male mice were immunized intraperitoneally (i.p.) with 10 µg of ovalbumin (OVA). This procedure was repeated at the 7th day of life, animals from the control group received i.p. injection of PBS only. Mice were exposed to either ambient PM2.5 or filtered air from the 5th to the 39th day of life, using an ambient particle concentrator developed at the Harvard School of Public Health (HAPC).Total RNA of lung samples (n=3 animals per group) was extracted using RNeasy Mini Kit (Qiagen, Hilden, Germany), according to manufacturer's instructions. The microarray analysis was performed using three RNA samples for each studied group (Control, OVA, PM2.5, OVA+PM2.5), totalizing 12 samples. One hundred nanograms of total RNA was amplified with the Ambion WT Expression Kit and hybridized onto the GeneChip Mouse Gene 2.0 ST Array (Thermo Scientific, Massachusetts, USA), following manufacturer’s protocol. The comparison between the control and OVA group exhibit 32 DEGs (28 up-regulated and 4 down-regulated), between the control and PM2.5 group had 6 DEGs (4 up and 2 down) and between the control and OVA+PM2.5 group had 5 DEGs (4 up and 1 down). The comparison between OVA and PM2.5 group showed 97 DEGS (22 up and 75 down) and between OVA and OVA+PM2.5 group had 7 DEGs (4 up and 3 down). Finally, the comparison between the PM2.5 and OVA+PM2.5 group exhibit 34 DEGs (2 up and 32 down).Our experimental data provide pathological support for the hypothesis that either allergic or environmental insults in early life have permanent adverse consequences to lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice.
Publication Title
Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.
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Treatment
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