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| Status |
Public on Dec 23, 2018 |
| Title |
Suppressor of cytokine signaling 1 is involved in gene regulation which control the survival of Ly6Clow monocytes in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Objective: Monocytes are crucially involved in inflammatory processes. In mice, different subsets of monocytes can be distinguished by the expression of Ly6C, a surface marker that is highly expressed on inflammatory monocytes (Ly6C high) and to a lesser extent on patrolling monocytes (Ly6C low). Our previous study revealed an aggravated accumulation of inflammatory Ly6C high monocytes in atherosclerotic-prone mice bearing a deficiency in suppressor of cytokine signaling (Socs)-1. In the present study, we performed a genome-wide analysis of Socs-1-dependent gene regulation in Ly6C high and Ly6C low monocytes. Methods and Results: Monocyte subsets were isolated from socs-1+/+ rag2‒/‒ ldlr–/‒ and socs-1‒/‒ rag2‒/‒ ldlr-‒/‒ mice with subsequent identification of differential regulated genes using illumina MouseWG-6 v2.0 Expression BeadChip microarrays (45,200 transcripts). Principal component analysis illustrates a distinct separation of gene expression profiles in Ly6C high and especially Ly6C low monocytes from Socs-1 deficient mice. Additionally, microarray data revealed 46 genes to be differentially regulated in a Socs-1 dependent manner in both monocytic subsets by 2-fold or more, some of which were validated by qPCR (p<0.05, n=4-6). Among them, two principal regulators of monocyte differentiation, C-X3-C chemokine receptor 1 (Cx3cr1) and colony stimulating factor 1 receptor (Csf1r), were identified to be Socs-1 dependently regulated. Especially for Csf1r a co-expression network for correlating Socs-1 dependent gene expression and protein interaction could be compiled. Furthermore, in silico analysis of a transcription factor (TF) network correlating with Socs-1 dependent mRNA expression data revealed a cluster of TF that includes Nr4a1 as well as several ets-domain proteins that may interact and thus regulate gene expression, inter alia regression of Csf1r. Conclusion: By genome-wide analysis, we could identify Cx3cr1 and Csf1r as two essential receptors mediating monocyte differentiation that are subjected to Socs-1 dependent transcription factor regulation.
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| Overall design |
Total RNA obtained from Ly6C high and Ly6C low monocytes isolated from bone marrow of atheroprone mice with 3 different genotypes (SRL-/-: Socs1-/- Rag2-/- Ldlr-/- ; RL-/-: Rag2-/- Ldlr-/-; L-/-: Ldlr-/-).
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| Contributor(s) |
Schütt J, Kreutz J, Grote K, Koch A, Schütt H, Oberoi R, Witten A, Stoll M, Schieffer B, Rühle F |
| Citation(s) |
30816678 |
| Submission date |
Sep 11, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Frank Rühle |
| E-mail(s) |
f.ruehle@imb-mainz.de
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| Organization name |
Institute of Molecular Biology (IMB)
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| Department |
Bioinformatics Core Facility
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| Street address |
Ackermannweg 4
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| City |
Mainz |
| ZIP/Postal code |
55128 |
| Country |
Germany |
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| Platforms (1) |
| GPL18752 |
Illumina MouseWG-6 v2.0 expression beadchip [gene symbol version] |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA404728 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE103705_RAW.tar |
52.5 Mb |
(http)(custom) |
TAR (of IDAT) |
| GSE103705_non-normalized.txt.gz |
6.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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