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GEO help: Mouse over screen elements for information. |
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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
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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.
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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
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Contributor(s) |
Cochain C, Arampatzi P, Saliba A, Ait-Oufella H |
Citation(s) |
36329047 |
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Submission date |
Oct 05, 2022 |
Last update date |
Jan 25, 2023 |
Contact name |
Antoine-Emmanuel Saliba |
E-mail(s) |
emmanuel.saliba@helmholtz-hzi.de
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Phone |
+49-931-31-81341
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Organization name |
Helmholtz Institute for RNA-based Infection Research
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Street address |
Josef-Schneider-Straße 2 / D15
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City |
Würzburg |
ZIP/Postal code |
97080 |
Country |
Germany |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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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 |
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Relations |
BioProject |
PRJNA887459 |
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 |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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