NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE120807 Query DataSets for GSE120807
Status Public on Jun 04, 2019
Title Genome-wide collaboration of canonical and non-canonical STAT1 complexes with NF-κB to control signal integration between Interferons and TLR4 in vascular and immune cells [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Atherosclerosis is a disease of large and medium-sized muscular arteries and is characterized by vascular inflammation and lipid-laden plaque formation within the intima of the vessel wall. Atherosclerosis is initiated by recruitment of blood leukocytes to the injured vascular endothelium and leads to altered contractility of Vascular Smooth Muscle Cells (VSMCs), acute and chronic luminal obstruction, abnormalities of blood flow and diminished oxygen supply to target organs. The pro-inflammatory pathways activated by Toll-like Receptors (TLRs), and Interferons (IFNs) have been identified as key components of atherogenesis. These pathways culminate in the activation of Signal Transducers and Activator of Transcription (STAT)1-containing complexes ISGF3 and GAF, and Nuclear factor-κB (NFκB) that coordinate expression of multiple chemokines, adhesion molecules, antiviral and antimicrobial proteins in vascular and immune cells. IFN-I and IFN-II participate in signaling cross-talk with TLR4 through combinatorial actions of ISGF3 and GAF with NF-kB leading to enhanced gene expression. Currently it is not clear how this signal integration is regulated at the genome-wide level and if similar mechanisms are activated by the different IFNs in vascular cells as compared to macrophages and dendritic cells.
Therefore, we compared genome-wide transcriptional responses of mouse VSMCs, macrophages (BMDMs) and dendritic cells (DCs) in response to IFNα, IFNγ or LPS alone, or after combined treatment using RNA-seq. Consequently, commonly up-regulated genes in VSMCs, BMDMs and DCs could be identified after combined treatment with IFNα+LPS, as well as after combined treatment with IFNγ+LPS. Generally, in all three cell-types combined treatment with IFNα+LPS or IFNγ+LPS resulted in a synergistic increase in gene expression as compared to single treatments. Also, significant functional overlap could be observed between commonly upregulated genes in response to IFNα+LPS and IFNγ+LPS. Using ChIP-seq on chromatin from VSMCs, STAT1 and p65 bound IFNα+LPS and IFNγ+LPS up-regulated genes were identified, containing GAF/GAS, ISGF3/ISRE or NF-kB binding motifs located in promoter regions, but also to up- and downstream genomic regions. Comparing IFNα+LPS and IFNγ+LPS commonly upregulated genes identified a substantial overlap of ISRE-containing genes. Interestingly, STAT1 as part of ISGF3 was shown to bind the promoter of these ISRE-containing genes in response to IFNα as well as IFNγ. Moreover, different binding modes of STAT1-p65 co-binding were detected, including GAS-NFκB, ISRE-NFκB or GAS-ISRE-NFκB, shared by IFNα+LPS and IFNγ+LPS up-regulated genes. This cooperative involvement involved a STAT1-dependent role in the nearby recruitment of p65 already upon single IFNα or IFNγ treatment, via closely located GAS-NFĸB or ISRE-NFĸB binding sites in promoter regions. More important, this STAT1-p65 co-binding was significantly increased upon subsequent LPS exposure and resulted in amplified transcriptional activity of IFNα+LPS and IFNγ+LPS upregulated genes.
 
Overall design RNA-seq samples were derived from IFN alpha- (8 hours), IFN gamma- (8 hours), LPS- (4hours), IFN alpha+LPS- and IFN gamma+LPS-treated Vascular Smooth Muscle Cells (VSMC), Bone Marrow-Derived Macrophages (BMDM) and Dendritic Cells (DC) at least in triplicates.
 
Contributor(s) Piaszyk-Borychowska A
Citation(s) 31231385
Submission date Oct 03, 2018
Last update date Sep 16, 2019
Contact name Anna Piaszyk-Borychowska
E-mail(s) [email protected]
Organization name Adam Mickiewicz University
Department Department of Human Molecular Genetics
Street address ul. Umultowska 89
City Poznań
ZIP/Postal code 61-614
Country Poland
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (81)
GSM3416176 unstimulated Vascular Smooth Muscle Cells [mm_VSMC_control_RS264]
GSM3416177 unstimulated Vascular Smooth Muscle Cells [mm_VSMC_control_RS268]
GSM3416178 unstimulated Vascular Smooth Muscle Cells [mm_VSMC_control_RS276]
This SubSeries is part of SuperSeries:
GSE120808 Genome-wide collaboration of canonical and non-canonical STAT1 complexes with NF-κB to control signal integration between Interferons and TLR4 in vascular and immune cells
Relations
BioProject PRJNA494591
SRA SRP163288

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary data files not provided
SRA Run SelectorHelp
Raw data are available in SRA
Processed data not provided for this record
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap