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SRP058850
Mus musculus
6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Aim: To determine the role of NOTCH during the response-to-injury and subsequent chronic inflammatory process of the arterial wall underlying atherosclerosis. Methods and results: We have generated an endothelial-specific RBPJK depleted mice using the Cdh5 cadherin promoter (ApoE-/-;RBPJflox/flox;Cdh5- CreERT). Endothelial-specific deletion of the Notch effector RBPJK or systemic deletion of the Notch1 receptor in athero-susceptible ApoE-/- mice fed a HC diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy revealed decreased leukocyte rolling on the endothelium of ApoE-/-;RBPJflox/flox;Cdh5- CreERT, that correlated with the lesser presence of leukocyts and macrophages in the vascular wall. Consistent with this, transcriptome analysis revealed that proinflammatory and endothelial activation pathways were downregulated in atherosclerotic tissue of RBPJk-mutant mice.. Jagged1 signaling upregulation in endothelial cells promotes the physical interaction and nuclear translocation of the intracellular domain of the Notch1 receptor (N1ICD) with NF-kB,. This N1ICD and NF-kB interaction is required for reciprocal transactivation of target genes including vascular cell adhesion molecule-1 (Vcam1). Conclusions: Notch signaling pathway inactivation decreases leukocyte rolling, thereby preventing endothelial dysfunction and vascular inflammation. Thus attenuating Notch signaling may constitute a useful therapeutic strategy for atherosclerosis. Key words: atherosclerosis, endothelium, signaling pathways, Notch, NF-kB, transcriptional regulation Overall design: RNA was isolated from the aortic arches of three ApoE-/-;RBPJflox/flox and three ApoE-/-; RBPJflox/flox;Cdh5-CreERTmice
Publication Title
Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- NextSeq 500
Description
We report here on G4RP-seq, which comprises of a cross-linking step, followed by chemical-affinity capture with the G4-specific small-molecule, BioTASQ and target identification using sequencing. This allows for capturing global snapshots of relative average levels of transiently folded G4-RNAs. We observed widespread G4-RNA targets indicative of transient G4 formation in several RNA entities in living human cells. G4RP-seq has also demonstrated that G4-stabilizing ligands (BRACO-19 and RHPS4) can change the G4 transcriptomic landscape, most notably in long non-coding RNAs. G4RP-seq thus provides a proof-of-principle for studying the G4-RNA landscape, as well as new ways of considering the mechanisms underlying G4-RNA formation and the activity of G4-stabilizing ligands. Overall design: Two BioTASQ-enriched samples and one input control for three different conditions (Untreated, BRACO-19-treated, and RHPS4-treated) in MCF7 cells
Publication Title
Transcriptome-wide identification of transient RNA G-quadruplexes in human cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Macrophages in tumor microenvironment have been characterized as M1- and M2-polarized subtypes. This study sought to investigate the effects of different macrophage subtypes on the biological behavior and global gene expression profiles of lung cancer cells. Expression microarray and bioinformatics analyses indicated that the different macrophage subtypes mainly regulated genes involved in cell cycle, cytoskeletal remodeling, coagulation, cell adhesion and apoptosis pathways in A549 cells, a pattern that correlated with the altered behavior of A549 cells observed after coculture with macrophage subtypes.
Publication Title
Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to identify patterns of gene expression associated with biological effects in THP-1 cells induced by F3, we performed a transcriptomic analysis on the THP-1 control and F3-treated THP-1 cells by oligonucleotide microarray
Publication Title
Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Individual genetic variation affects gene expression and cell phenotype by acting within complex molecular circuits, but this relationship is still largely unknown. Here, we combine genomic and meso-scale profiling with novel computational methods to detect genetic variants that affect the responsiveness of gene expression to stimulus (responsiveness QTLs) and position them in circuit diagrams. We apply this approach to study individual variation in transcriptional responsiveness to three different pathogen components in the model response of primary bone marrow dendritic cells (DCs) from recombinant inbred mice strains. We show that reQTLs are common both in cis (affecting a single target gene) and in trans (pleiotropically affecting co-regulated gene modules) and are specific to some stimuli but not others. Leveraging the stimulus-specific activity of reQTLs and the differential responsiveness of their associated targets, we show how to position reQTLs within the context of known pathways in this regulatory circuit. For example, we find that a pleiotropic trans-acting genetic factor in chr1:129-165Mb affects the responsiveness of 35 anti-viral genes only during an anti-viral like stimulus. Using RNAi we uncover RGS16 the likely causal gene in this interval, and an activator of the antiviral response. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in other complex circuits in primary mammalian cells.
Publication Title
Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Tfh and B cells were cultured together with or without Tfr cells. After 4 days Tfh and B cells were sorted and prepared for 3'' targeted RNA-seq. Overall design: Examination of transcriptional changes upon suppression of Tfh and B cells.
Publication Title
Suppression by T<sub>FR</sub> cells leads to durable and selective inhibition of B cell effector function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Tfh and B cells were cultured together with or without Tfr cells and IL-21. After 4 days Tfh and B cells were sorted and prepared for 3'' targeted RNA-seq. Overall design: Examination of transcriptional changes upon IL-21 rescue of B cell suppression
Publication Title
Suppression by T<sub>FR</sub> cells leads to durable and selective inhibition of B cell effector function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The CLS1/CAF co-culture maintained the cancer stemness. This cancer stemness was lost when the CAF feeder cells were removed during passaging.
Publication Title
Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The mammary gland at early stages of pregnancy undergoes fast cell proliferation, yet the mechanism to ensure its genome integrity is largely unknown. Here we show that pregnancy enhances expression of genes involved in numerous pathways, including most genes encoding replisomes. In mouse mammary glands, replisome genes are positively regulated by estrogen/ERa signaling but negatively regulated by BRCA1. Upon DNA damage, BRCA1 deficiency markedly enhances DNA replication initiation. BRCA1 deficiency also preferably impairs DNA replication checkpoints mediated by ATR and CHK1 but not by WEE1, which inhibits DNA replication initiation through CDC7-MCM2 pathway and enables BRCA1-deficient cells to avoid further genomic instability. Thus, BRCA1 and WEE1 inhibit DNA replication initiation in a parallel manner to ensure genome stability for mammary gland development during pregnancy.
Publication Title
BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
- Ion Torrent Proton
Description
We report the high-throughput profiling of brain RNA from three Drosophila stains: dBRWD3PX2/+, dBRWD3PX2/PX2 and dBRWD3PX2/PX2, yemGS21861/GS21861. By obtaining over 50 million reads of sequence, WE compared the transcriptomic differences among the brains from these three stains. We found that the expression of 871 genes was significantly different between heterozygous control and homozygous dBRWD3 mutant brains (484 upregulated genes, 387 downregulated genes, p<0.05). Gene ontology (GO) analysis of the 871 genes revealed a broad spectrum of biological processes, ranging from synaptic activity to housekeeping metabolism subjective to dBRWD3 regulation. Among the 387 downregulated genes, the expression of 360 genes (92.8%) was increased in the dBRWD3, yem double mutant brains compared with dBRWD3 mutant. Among the 484 upregulated genes, the expression of 412 genes (85.1%) was decreased in the double mutant brains. These differential genes were evenly distributed on X chromosome and autosomes (149 on X, 178 on 2L, 154 on 2R, 166 on 3L, and 207 on 3R). These analyses indicate that dBRWD3 regulates gene expression in the brain mainly through the HIRA/YEM complex. Overall design: Examination of brain transcriptome in 3 Drosophila strains.
Publication Title
Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples