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Series GSE214880 Query DataSets for GSE214880
Status Public on Oct 26, 2022
Title scRNA-seq/CITE-seq analysis of aortic CD45+ cells from mice expressing Jak2V617F mutation in myeloid cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development and complications remains unknown. In a cohort of patients with myeloproliferative neoplasm, JAK2V617F mutation was identified as an independent risk factor for dilation of both the ascending and descending thoracic aorta. Using single-cell RNA-seq, complementary genetically-modified mouse models, as well as pharmacological approaches, we found that JAK2V617F mutation was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages, and dissecting aneurysm through the recruitment of circulating monocytes at later stages. Finally, genetic manipulation of tissue-resident macrophages, or treatment with a Jak2 inhibitor, ruxolitinib, mitigated aortic wall inflammation and reduced aortic dilation and rupture. Overall, JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.
Overall design Aortic CD45+ cells were sorted from control mice (Jak2-WT; n=5) and mice with a myeloid specific expression of mutated JAK2 variant Jak2V617F (Jak2-V617F-MyC; n=5) and processed for scRNA-seq with CITE-seq
Contributor(s) Cochain C, Arampatzi P, Saliba A, Ait-Oufella H
Citation(s) 36329047
Submission date Oct 05, 2022
Last update date Jan 25, 2023
Contact name Antoine-Emmanuel Saliba
Phone +49-931-31-81341
Organization name Helmholtz Institute for RNA-based Infection Research
Street address Josef-Schneider-Straße 2 / D15
City Würzburg
ZIP/Postal code 97080
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (3)
GSM6617294 Aortic CD45+, WT and myeloid JAK2-V617F, GEX
GSM6617295 Aortic CD45+, WT and myeloid JAK2-V617F, ADT
GSM6617296 Aortic CD45+, WT and myeloid JAK2-V617F, HTO
BioProject PRJNA887459

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Supplementary file Size Download File type/resource
GSE214880_barcodes.tsv.gz 35.5 Kb (ftp)(http) TSV
GSE214880_features.tsv.gz 254.8 Kb (ftp)(http) TSV
GSE214880_matrix.mtx.gz 62.7 Mb (ftp)(http) MTX
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Processed data are available on Series record

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