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GSE9097
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We are investigating the transcriptional response of mice infected with Helicobacter hepaticus and links to liver cancer
Publication Title
Genetic susceptibility to chronic hepatitis is inherited codominantly in Helicobacter hepaticus-infected AB6F1 and B6AF1 hybrid male mice, and progression to hepatocellular carcinoma is linked to hepatic expression of lipogenic genes and immune function-associated networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions. F4/80-positive ATMs were isolated from obese vs lean mice. High-fat feeding of wild-type mice and myeloid-specific Hif1-/- mice was used to examine the role of hypoxia-inducible factor-1 (HIF-1) in ATMs part of obese adipose tissue. In vitro, bone marrow-derived macrophages were co-cultured with adipose tissue explants to examine adipose tissue-induced changes in macrophage phenotypes. Transcriptome analysis, real-time flux measurements, ELISA and several other approaches were used to determine the metabolic signatures and inflammatory status of macrophages. In addition, various metabolic routes were inhibited to determine their relevance for cytokine production. Transcriptome analysis and extracellular flux measurements of mouse ATMs revealed unique metabolic rewiring in obesity characterised by both increased glycolysis and oxidative phosphorylation. Similar metabolic activation of CD14+ cells in obese individuals was associated with diabetes outcome. These changes were not observed in peritoneal macrophages from obese vs lean mice and did not resemble metabolic rewiring in M1-primed macrophages. Instead, metabolic activation of macrophages was dose-dependently induced by a set of adipose tissue-derived factors that could not be reduced to leptin or lactate. Using metabolic inhibitors, we identified various metabolic routes, including fatty acid oxidation, glycolysis and glutaminolysis, that contributed to cytokine release by ATMs in lean adipose tissue. Glycolysis appeared to be the main contributor to the proinflammatory trait of macrophages in obese adipose tissue. HIF-1, a key regulator of glycolysis, nonetheless appeared to play no critical role in proinflammatory activation of ATMs during early stages of obesity. Our results reveal unique metabolic activation of ATMs in obesity that promotes inflammatory cytokine release. Further understanding of metabolic programming in ATMs will most likely lead to novel therapeutic targets to curtail inflammatory responses in obesity.
Publication Title
Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Uncontrolled microglial activation may lead to development of inflammation-induced brain damage. Here we uncover a ribosome-based mechanism/check point involved in control of the innate immune response and microglial activation. Using an in vivo model-system for analysis of the dynamic translational state of microglial ribosomes with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly up-regulated and ribosome-associated mRNAs were not translated resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA and immunomodulatory/homeostatic protein signature. We find that this is due to specific translational suppression of highly expressed mRNAs through a 3UTR-mediated mechanism involving the RNA binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia.
Publication Title
Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarray profiling to document the difference between telomerase+ vs. ALT+ T-cell lymphomas developed on G3 Atm-/-TERT-ER genetic background.
Publication Title
Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Molecular mechanisms that are responsible for the development of human skin epithelial cells are not completely understood so far. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSC) remains poor. Using an approach including RNA interference and high-throughput imaging of early epithelial cells, we could identify candidate kinases which are involved in skin epithelial differentiation. Among them, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors, increased the amount of generated keratinocytes and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins. Our data bring substantial input in the regulation of human skin epithelial differentiation and for improving differentiation protocols from pluripotent stem cells.
Publication Title
An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 5 Downloadable Samples
Illumina HiSeq 2000
Description
Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Overall design: RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.
Publication Title
Altered enhancer transcription underlies Huntington's disease striatal transcriptional signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 48 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The size and scope of microarray experiments continue to increase. However, datasets generated on different platforms or at different centres contain biases. Improved techniques are needed to remove platform- and batch-specific biases. One experimental control is the replicate hybridization of a subset of samples at each site or on each platform to learn the relationship between the two platforms. To date, no algorithm exists to specifically use this type of control. LTR is a linear-modelling-based algorithm that learns the relationship between different microarray batches from replicate hybridizations. LTR was tested on a new benchmark dataset of 20 samples hybridized to different Affymetrix microarray platforms. Before LTR, the two platforms were significantly different; application of LTR removed this bias. LTR was tested with six separate data pre-processing algorithms, and its effectiveness was independent of the pre-processing algorithm. Sample-size experiments indicate that just three replicate hybridizations can significantly reduce bias. An R library implementing LTR is available.
Publication Title
LTR: Linear Cross-Platform Integration of Microarray Data.
Sample Metadata Fields
Sex
View Samples- Oryza sativa
- 35 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
affy_rice_2011_03 - affy_compartimentation_rice_albumen_embryon - During germination, the rice seed goes from a dry quiescent state to an active metabolism. As with all cereals, the rice seed is highly differentiated between the embryo (that will give rise to the future plantlet) and the endosperm (that contains the seed storage compounds and that will degenerate). The molecular mechanisms operating in the rice seed embryo have begun to be described. Yet, very few studies have focused specifically on the endosperm during the germination process. In particular, the endosperm is mostly addressed with regards to its storage proteins but we have detected a large protein diversity by two-dimensional electrophoresis. Similarly, the endosperm is rich in total RNA which suggest that gene expression coming from seed maturation could play a role during the germination process. In this context, we want to compare the transcriptome of the embryo and the endosperm during rice seed germination. -We germinate rice seeds of the first sequenced rice cultivar i.e. Nipponbare during 0, 4, 8, 12, 16 and 24h of imbibition in sterile distilled water. Germination occurs under constant air bubbling, in the dark at 30C. These rice seeds are then manually dissected into embryo and endosperm fractions. -The embryo-derived samples are abbreviated in E while the endosperm samples are abbreviated A. The germination time-point is indicated after the letter (e.g. E8 for embryo samples harvested after 8 hours of germination). Finally, the biological repetition number is indicated before the letter and the time digit (e.g. 1-E8 for an embryo sample from the first repetition at 8 hours of imbibition).
Publication Title
Compartmentation and dynamics of flavone metabolism in dry and germinated rice seeds.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
The AIL transcription factor BABY BOOM (BBM) is required together with the related PLETHORA proteins for embryo and root meristem development and its expression is sufficient to confer pluripotency and totipotency to somatic tissues. We show that BBM and other AIL proteins interact with multiple members of the L1/epidermal-expressed HD-ZIP class IV / HOMEODOMAIN GLABROUS (HDG) transcription factor family. Ectopic overexpression of HDG1, HDG11 and HDG12 genes induces a reduced growth phenotype, and analysis of HDG1 overexpression lines shows that this growth reduction is due to both root and shoot meristem arrest. To understand how HDG1 controls cell proliferation, as well as its functional relationship with BBM, we performed microarray experiments to identify candidate genes that are directly regulated by HDG1, and compared these to the set of genes that are directly regulated by BBM expression.
Publication Title
AIL and HDG proteins act antagonistically to control cell proliferation.
Sample Metadata Fields
Specimen part, Treatment
View Samples