Heart ventricle tissue was harvested from Trex1/RAG2 DKO mice and from Trex1WT/RAG2KO littermate controls. RNA was extracted, and an Affymetrix Mouse 430 2.0 gene chip analysis was performed.
Trex1 prevents cell-intrinsic initiation of autoimmunity.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Treatment, Time
View SamplesAnalysis of ALR-deficient cells indicates that ALRs are not required for the IFN response to intracellular DNA. To explore whether AIM2-like receptors activated another innate signaling pathway upon
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Treatment, Time
View SamplesCellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling rapidly shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol, and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity. Overall design: shRNA to SREBF1 (shSREBP1) or SREBF2 (shSREBP2) were stably introduced via 3rd generation lentivirus into human THP1 monocytic cells under puromycin selection. Non-targeting shRNA scramble was used for a control (shControl). shControl, shSREBP1 and shSREBP2 modified cell types were analyzed by RNA-seq in duplicate.
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling.
No sample metadata fields
View SamplesWe performed mRNA-seq from hand-dissected fat body tissue from 68hr (after egg laying, AEL) and 92hr AEL Drosophila melanogaster larvae. Fat body was dissected from wild-type (OrR) males and testes were removed. We examined gene expression genome-wide with particular focus on genes in the underreplicated regions in the fat body. Overall design: Sequencing of poly-A selected RNA from 68hr AEL and 92hr AEL wild-type (OrR) Drosophila melanogaster male larvae. Sequences analyzed by Illumina sequencing. Two biological replicates are included for each developmental sample.
Dynamic changes in ORC localization and replication fork progression during tissue differentiation.
Sex, Specimen part, Subject
View SamplesWe employed miRNA-seq to profile all miRNAs from a pure population of hand-dissected polyploid TGCs from embryonic day 9.5. These data set of polyploid-specific TGCs microRNAs will provide insights into TGCs differentiation and endoreplication. Overall design: TGCs were micro-dissected from day E9.5 nine implantation sites from C57BL/J6 mice. The portion of the TGCs in direct contact with the spongiotrophoblast layer and the labyrinth layer were manually removed to avoid collecting any polyploid cells from the former or multi-nucleated syncytiotrophoblast cells from the latter.
Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells.
Specimen part, Cell line
View SamplesWe employed RNA-seq to transcriptionally profile a pure population of hand-dissected polyploid TGCs from embryonic day 9.5. These data provide a set of polyploid-specific TGCs transcripts that will aid in the understanding of TGCs differentiation and endoreplication. Overall design: TGCs were micro-dissected from day E9.5 nine implantation sites from C57BL/6J mice. The portion of the TGCs in direct contact with the spongiotrophoblast layer and the labyrinth layer were manually removed to avoid collecting any polyploid cells from the former or multi-nucleated syncytiotrophoblast cells from the latter.
Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells.
Specimen part, Cell line
View SamplesTIMP-2 is an endogenous angiogenesis inhibitor, i.e. inhibits endothelial cell proliferation and tumor angiogenesis. As a result, TIMP-2 inhibits tumor growth and progression to metastasis. Understanding, therefore, the mechanisms of TIMP-2-mediated tumor growth inhibition would provide further support on the use of TIMP-2 as a novel biological agent for cancer therapy. We used microarray analysis to determine the TIMP-2 and Ala+TIMP-2 transcriptional profiles of A549 cancer cells in order to understand how TIMP-2 inhibits tumor growth and angiogenesis.
TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells.
Specimen part, Cell line
View SamplesIn Caenorhabditis elegans, VA and VB motor neurons arise as lineal sisters but synapse with different interneurons to regulate locomotion. VA-specific inputs are defined by the UNC-4 homeoprotein and its transcriptional corepressor, UNC-37/Groucho, which function in the VAs to block the creation of chemical synapses and gap junctions with interneurons normally reserved for VBs. To reveal downstream genes that control this choice, we have employed a cell-specific microarray strategy that has now identified unc-4-regulated transcripts. One of these genes, ceh-12, a member of the HB9 family of homeoproteins, is normally restricted to VBs. We show that expression of CEH-12/HB9 in VA motor neurons in unc-4 mutants imposes VB-type inputs. Thus, this work reveals a developmental switch in which motor neuron input is defined by differential expression of transcription factors that select alternative presynaptic partners. The conservation of UNC-4, HB9, and Groucho expression in the vertebrate motor circuit argues that similar mechanisms may regulate synaptic specificity in the spinal cord.
UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans.
Specimen part
View SamplesThe goal of this experiment is to characterize the ability of IRAK4 kinase inhibitors to block TLR7 or TLR9 induced gene transcription in human PBMCs. PBMCs from two donors were pretreated with compound for 30 minutes and stimulated with gardiquimod (TLR7 ligand) or ODN 2216 (TLR9 ligand) for 5 hrs. Compound treated gene expression profiles wil be compared to untreated.
Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity.
Specimen part, Subject
View Samples