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Series GSE152198 Query DataSets for GSE152198
Status Public on Jun 11, 2020
Title IRF5 promotes intestinal inflammation by guiding monocyte differentiation towards pathogenic CD11c+ macrophage phenotype [scrnaseq_steady_state]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Mononuclear phagocytes (MNPs) play a key role in maintaining intestinal homeostasis but also in triggering immunopathology in response to acute microbial stimulation, which induces the recruitment of masses of Ly6Chi monocytes to the gut. The regulators that control monocyte tissue adaptation in the gut remain poorly understood. Interferon Regulatory Factor 5 (IRF5) is a transcription factor previously shown to play a key role in maintaining the inflammatory phenotype of macrophages Here we investigate the impact of IRF5 on the MNP system and physiology of the gut at homeostasis and during inflammation. We demonstrate that IRF5 deficiency has a limited impact on colon physiology at steady state, but ameliorates immunopathology during Helicobacter hepaticus induced colitis. Inhibition of IRF5 activity in MNPs phenocopies global IRF5 deficiency. Using a combination of bone marrow chimera and single cell RNA-sequencing approaches we compare the differentiation trajectories of wild type and IRF5 deficient monocytes in a shared inflammatory environment and demonstrate that IRF5 stipulates a choice in monocyte differentiation towards macrophages. Specifically, IRF5 promotes the generation of pathogenic CD11c+ macrophages and controls the production of inflammatory mediators by these cells. Thus, we identify IRF5 as a key transcriptional controller of pathogenic monocyte differentiation in the gut.
Overall design Mixed bone marrow chimeras (mice) were constructed using wildtype (CD45.1+ve) and Irf5 knockout (CD45.2+ve) cells that were also heterozygous for knock-in of GFP to the CX3CR1 locus. The steady state blood and cLP scRNA-seq datasets were generated in the same experiment from a set of MBMCs (n=5, cells pooled from all animals for both analyses).
Contributor(s) Corbin AL, Gomez-Vazquez M, Attar M, Udalova IA, Sansom SN
Citation(s) 32444476
Submission date Jun 10, 2020
Last update date Sep 10, 2020
Contact name Stephen Sansom
Organization name Kennedy Institute of Rheumatology
Department NDORMS
Lab Sansom
Street address Roosevelt Drive
City Oxford
State/province Oxfordshire
ZIP/Postal code OX3 7FY
Country United Kingdom
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM4608937 cLP_mph_wt_ss
GSM4608938 cLP_mph_ko_ss
GSM4608939 pbmc_mono_wt_ss
This SubSeries is part of SuperSeries:
GSE129258 IRF5 promotes intestinal inflammation by guiding monocyte differentiation towards pathogenic CD11c+ macrophage phenotype
BioProject PRJNA638619
SRA SRP266783

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Supplementary file Size Download File type/resource
GSE152198_barcodes.tsv.gz 109.8 Kb (ftp)(http) TSV
GSE152198_genes.tsv.gz 468.3 Kb (ftp)(http) TSV
GSE152198_matrix.mtx.gz 144.3 Mb (ftp)(http) MTX
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Raw data are available in SRA
Processed data are available on Series record

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