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SRP033554
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Macrophages polarize to divergent functional phenotypes depending on their microenvironment in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified 7 major (novel and known) regulatory modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included: inflammatory variant of the aspartate-arginosuccinate shunt; TCA cycle break at Idh expression accompanied by citrate accumulation and production of itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine in polarization, providing nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation results in significant M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization. Overall design: Bone-marrow derived macrophages were generated from C57BL/6 mice were plated at ~100k cells per well in 96-well plate and stimulated with either Il4 or combination of LPS&IFNg or left unstimulated for 24 h mRNA was derived from lysates using Invitrogen oligo-dT beads
Publication Title
Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Survival of insects on a substrate containing toxic substances such as plant secondary metabolites or insecticides is dependent on the metabolism or excretion of those xenobiotics. The primary sites of xenobiotic metabolism are the midgut, Malpighian tubules and fat body. In general, these organs are treated as single tissues by online databases, but several studies have shown that gene expression within subsections of the midgut is compartmentalized. In this article, RNA sequencing analysis was used to investigate whole-genome expression in subsections of the third-instar larval midgut. The results support functional diversification in subsections of the midgut. Analysis of the expression of gene families that are implicated in the metabolism of xenobiotics suggests that metabolism may not be uniform along the midgut. These data provide a starting point for investigating gene expression and xenobiotic metabolism in the larval midgut. Overall design: Examination of expression in eight samples corresponding to compartments of gene expression in the midgut
Publication Title
Whole-genome expression analysis in the third instar larval midgut of Drosophila melanogaster.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 3000
Description
Metabolic engagement is intrinsic to immune cell function. Prostaglandin E2 (PGE2) has been shown to modulate macrophage activation, yet how PGE2 might affect metabolism is unclear. Here we show that PGE2 causes mitochondrial membrane potential (??m) to dissipate in interleukin-4 activated macrophages (M(IL-4)). Effects on ??m are a consequence of PGE2-initiated transcriptional regulation of genes in the malate-aspartate shuttle (MAS), particularly GOT1. Reduced ??m causes alterations in the expression of 126 voltage regulated genes (VRGs) including Resistin like molecule-a (RELMa), a key marker of M(IL-4), and genes that regulate cell cycle. The transcription factor ETS variant 1 (ETV1) plays a role in the regulation of 38% of the VRGs. These results reveal ETV1 as a ??m-sensitive transcription factor, and ??m as a mediator of mitochondrial-directed nuclear gene expression. Overall design: RNA-seq was performed on bone marrow derived macrophages (triplicate) exposed to IL-4 alone or in combination with PGE2 or Valinomycin plus no stimulation controls. In addition, RNA-seq was performed on bone marrow derived macrophages stimulated in the same way as before, however the transcription factor ETV1 was knocked down.
Publication Title
Mitochondrial Membrane Potential Regulates Nuclear Gene Expression in Macrophages Exposed to Prostaglandin E2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 94 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Affymetrix HG_U133 array sets (A and B chips) were used to determine the whole genome transcription profile of clinically documented and neuropathologically confirmed cases of sporadic Parkinson's disease as well as controls.
Publication Title
Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 54 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We analyzed the transcriptome of dormant and after-ripened imbibed seeds of the Arabidopsis accession Cape verde Islands.
Publication Title
Dormant and after-Ripened Arabidopsis thaliana Seeds are Distinguished by Early Transcriptional Differences in the Imbibed State.
Sample Metadata Fields
Specimen part, Time
View Samples- Caenorhabditis elegans
- 45 Downloadable Samples
- Illumina HiSeq 2500
Description
We conducted a time series of transcriptomics measurements during normal ageing in C. elegans in two non-reproductive strains (fem and gem) during normal ageing (days 1 to 10 of adulthood) and used this together with a multi-omics modelling pipeline to explore the changes that take place due to ageing. Overall design: Two strains and several time points with three replicates per strain and time point.
Publication Title
Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During <i>C. elegans</i> Aging.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
We used an inducible shRNA system and RNA-Seq to examine gene expression changes in acute myeloid leukemia THP1 cells following silencing of RUVBL2. RUVBL2 is a AAA+ ATPase that functions in a number of cellular processes, including chromatin remodeling and transcriptional control, and is critical for survival of acute myeloid leukemia cells and in vivo disease progression. Overall design: Total cellular RNA was extracted using the RNeasy Plus Mini Kit from THP1 cells transduced with RUVBL2-specific inducible shRNA, following 2 and 4 days exposure to doxycycline or medium controls. In total, 6 pairs of control and doxycycline-treated samples were analysed (3 control and 3 doxycycline-treated for each time-point).
Publication Title
The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We have determined that verticillin A is a histone methyltransfease inhibitor that selectively inhibits human SUV39H1, SUV39H2, G9a and GLP to inhibit H3K9 methylation in human colon cancer cells. The objective here is to identify verticillin A target genes in human colon cancer cells.
Publication Title
H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
These studies utilized two TCR transgenic mouse lines, LLO118 and LLO56, that our laboratory has developed and characterized, which recognize the same Listeria monocytogenes LLO/IO-Ab epitope with equal affinities. When 104 naive CD4+ LLO T cells are transferred into a B6 mouse and one day later infected with wild type Listeria monocytogenes, the LLO118 T cells have a more robust primary expansion than LLO56. In contrast, after a secondary challenge, LLO56 T cells have a much greater expansion than LLO118 T cells. One striking phenotypic difference between the LLO118 and LLO56 T cells lies in their CD5 expression. CD5 expression has been shown to correlate directly with TCR affinity for self-pMHC and tonic signaling. LLO56 cells have a higher basal phosphorylation of the TCR chain, and they have significantly increased expression of Nur77 mRNA. These transcriptional profiling experiments examined if there were transcriptional differences between LLO118 and LLO56 T cells, either naive or after D7 of infection, that would account for their disparate in vivo behaviors.
Publication Title
Tonic TCR Signaling Inversely Regulates the Basal Metabolism of CD4<sup>+</sup> T Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Autophagy genes play an important role in the T cell activation and proliferation. We examined the role of ATG7 during the process of CD8 T cell memory formation. In the absence of ATG7, antigen-specific CD8 T cells failed to survive past the contraction phase and failed to give rise to memory cells.
Publication Title
Autophagy is essential for effector CD8(+) T cell survival and memory formation.
Sample Metadata Fields
Specimen part
View Samples