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SRP089860
Mus musculus
16 Downloadable Samples
NextSeq 500
Description
Intracellular trafficking is essential for proper cell signaling. In the pancreas, secretory cells rely on trafficking to regulate blood glucose and digestion. Pancreatic disorders reflect defects in function or development, evoking considerable interest in understanding the molecular genetics governing pancreatic organogenesis. Here, we show the transcription factor NFIA regulates trafficking in both the embryonic and adult pancreas, affecting both developmental cell fate decisions and adult physiology. NFIA deletion from pancreatic progenitors led to the development of more acinar cells and ducts and fewer endocrine cells, whereas ectopic NFIA promoted endocrine formation. We found that NFIA's effects on trafficking influence endocrine/exocrine cell fate decisions through regulation of Notch. Adult NFIA-deficient mice develop diabetic phenotypes due to impaired insulin granule trafficking and defects in acinar zymogen secretion. This study shows how a single transcription factor, NFIA, thus exerts profound effects on both embryonic cell fate and adult physiology by regulating vesicle trafficking. Overall design: 2 control and 2 NFIA fl/fl; Pdx1-cre samples, from pooled embryonic litters at E17.5
Publication Title
Pancreatic Cell Fate Determination Relies on Notch Ligand Trafficking by NFIA.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptome analysis of RNA extracted from human induced pluripotent stem cell (hipsc)-derived neurons exposed to botulinum neurotoxin type A1 (BoNT/A1) and an atoxic derivative, BoNT/A ad.
Publication Title
Analysis of gene expression in induced pluripotent stem cell-derived human neurons exposed to botulinum neurotoxin A subtype 1 and a type A atoxic derivative.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 29 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Light initiates the seedling deetiolation transition by promoting major changes in gene expression mainly regulated by phytochrome (phy) photoreceptors. During the initial dark-to-light transition, phy photoactivation induces rapid changes in gene expression that eventually lead to the photomorphogenic development. Recent reports indicate that this process is achieved by phy-induced degradation of Phy-Interacting bHLH transcription Factors (PIFs) PIF1, PIF3 PIF4 and PIF5, which are partly redundant constitutive repressors of photomorphogenesis that accumulate in darkness. In order to test whether light/phy-regulated gene expression occurs through these PIFs, we have performed whole-genome expression analysis in the pif1pif3pif4pif5 quadruple mutant (pifq).
Publication Title
Definition of early transcriptional circuitry involved in light-induced reversal of PIF-imposed repression of photomorphogenesis in young Arabidopsis seedlings.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-seq experiment of WT and pifq mutant seedlings grown for 3 days in darkness in presence or absence of Lincomycin. Overall design: Transcriptome profiles of the wild-type (WT) and pif1pif3pif4pif5 (pifq) quadruple mutant seedlings grown for 3 days in the dark in presence or absence of Lincomycin. Biological triplicate samples were analyzed from libraries constructed using a 3''-capture, 5'' to 3'' directional method.
Publication Title
Phytochrome and retrograde signalling pathways converge to antagonistically regulate a light-induced transcriptional network.
Sample Metadata Fields
Subject
View Samples- Pseudomonas aeruginosa
- 4 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Quorum sensing (QS) is a mechanism of bacterial gene regulation in response to increases in population density. Production of small molecule QS signals, their accumulation within a diffusion-limited environment and their binding to the LuxR-type receptor trigger QS-controlled gene regulatory cascades. QS pathways mediated by acylhomoserine lactones (AHLs) in Gram-negative bacteria are the best studied. In Pseudomonas aeruginosa, for example, binding of AHLs to their cognate receptors (LasR, RhlR) controls production of virulence factors, pigments, antibiotics and other behaviors important for its interactions with eukaryotic hosts and other bacteria. We isolated a new small cyclopropane-containing fatty acid, lyngbyoic acid (1), as a major metabolite of the marine cyanobacterium, Lyngbya sp., collected off Fort Pierce, Florida. The structure of 1 was determined by NMR, MS and optical rotation. We screened 1 against four reporters based on AHL receptors from Vibrio fischeri (LuxR), Aeromonas hydrophila (AhyR), Agrobacterium tumefaciens (TraR) and P. aeruginosa (LasR) and found that 1 most strongly affected LasR. We show, by using a defined set of reporters, that compound 1 acts both through the AHL-binding site of LasR and independent of it. We also show that 1 reduces pyocyanin and LasB, both on the protein and transcript level, in wild-type P. aeruginosa, and that 1 directly inhibits LasB enzymatic activity. Conversely, dodecanoic acid (11) increased pyocanin and LasB, demonstrating that 1 is a tagged fatty acid potentially resistant to -oxidation.
Publication Title
Lyngbyoic acid, a "tagged" fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 29 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants respond to changes in the red:far red ratio (R:FR) of incident light. A reduction in this ratio (increase in FR) results in the Shade Avoidance Response (SAR) with associated changes in gene expression. The Phyotchrome-Interacting Factors (PIFs) are bHLH transcription factors known to be involved in the SAR. An analysis of changes in gene expression in WT and quadruple pif1pif3pif4pif5 (pifq; Leivar et al., 2008 (PMID 19920208)) mutant seedlings in response to an increase in FR should identify primary targets of PIF signaling.
Publication Title
Dynamic antagonism between phytochromes and PIF family basic helix-loop-helix factors induces selective reciprocal responses to light and shade in a rapidly responsive transcriptional network in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 21 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
PIF3 plays a role as repressor of photomorphogenesis in darkness. To identify PIF3-regulated genes that might be implementing this action, we have performed whole-genome expression analysis in the pif3 mutant.
Publication Title
Functional profiling identifies genes involved in organ-specific branches of the PIF3 regulatory network in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
A cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream from ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the primary tumors arising in the native transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found PD-L1 expression in the tumors and in vitro. In conclusion these data document the validity and utility of this cell line for in vivo preclinical immunotherapy trials. Overall design: Flash frozen NDL(UCD) cell line tumor transplants were sampled and whole-transcriptome analysis was performed by next-generation sequencing (NGS)-based RNA-Sequencing. This series includes three biological replicates of the same cell line grown in three different (but same strain) mouse.
Publication Title
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Epigenetic and metabolic reprogrammings are implicated in cancer progression with unclear mechanisms. We report here that the histone methyltransferase NSD2 drives cancer cell and tumor resistance to therapeutics such as tamoxifen, doxorubicin, and radiation by reprogramming of glucose metabolism. NSD2 coordinately up-regulates expression of TIGAR, HK2 and G6PD and stimulates pentose phosphate pathway (PPP) production of NADPH for ROS reduction. We discover that elevated expression of TIGAR, previously characterized as a fructose-2,6-bisphosphatase, is localized in the nuclei of resistant tumor cells where it stimulates NSD2 expression and global H3K36me2 mark. Mechanistically, TIGAR interacts with the antioxidant regulator Nrf2 and facilitates chromatin assembly of Nrf2-H3K4me3 methylase MLL1 and elongating Pol-II, independent of its metabolic enzymatic activity. In human tumors, high levels of NSD2 correlate strongly with early recurrence and poor survival and are associated with nuclear-localized TIGAR. This study defines a nuclear TIGAR-mediated, epigenetic autoregulatory loop functioning in redox rebalance for resistance to tumor therapeutics. Overall design: A total of 4 samples were analyzed in this study. The study included two cell lines, MCF7 and the tamoxifen-resistant subline TMR. Both were were cultured in medium containing vehicle control and/or 4-hydroxytamoxifen (Tam). The untreated MCF7 and TMR cell lines served as controls for the study.
Publication Title
Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
[Gro-seq] Precursor B acute leukemia cells measured using global nuclear run-on sequencing [ChIP-Seq] The genome-wide occupancy of ser2 and ser5 phosphorylated RNA pol2 and H3K4me3 was measured in precursor B acute leukemia cells measured using chip-seq. Overall design: [Gro-seq] Nascent RNA expression profiles were generated at cells in various basal culture conditions. [ChIP-Seq] Performed from REH and Nalm6 cells cultured under basal culture conditions. Mnase digestion was used for DNA fragmentation. Antibodies against Ser2 and Ser5 phosphorylated RNA polymerase and H3K4me3 compared to input. ****************************** This study includes reanalysis of Samples in Series GSE39878 (GSM980645, GSM980644), GSE60454 (GSM1480326), and GSE41009 (GSM1006728, GSM100672). The processed data files for the reanalyses are linked to GSE67540 as supplementary files (see the GSE67540_README.txt file for additional information).
Publication Title
Transcription-coupled genetic instability marks acute lymphoblastic leukemia structural variation hotspots.
Sample Metadata Fields
No sample metadata fields
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