|
| Status |
Public on Jul 13, 2023 |
| Title |
The role of stromal and immune cells in atrial disease [II] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In atrial fibrillation, disturbed electrical conduction disrupts the coordinated contraction of the heart’s antechambers, increasing the risk of stroke and heart failure. The rising prevalence of this disease approaches 9% in patients >65 years. Studying freshly isolated human atrial tissue and a new mouse model, we here decipher how immune and stromal cells contribute to the structural tissue remodeling that underlies atrial fibrillation. Single-cell transcriptomes from control and diseased human atria documented macrophage doubling at the expense of endothelial and mural cells. An inflammatory monocyte and a pro-fibrotic SPP1+ macrophage cluster expanded in patients with atrial fibrillation. To experimentally perturb pathways observed in patients, we matched their risk factors Hypertension, Obesity and Mitral valvE Regurgitation (HOMER) in mice. Atrial single-cell transcriptomes obtained in HOMER mice, which developed enlarged, fibrillation-prone atria, recapitulated human cell composition and transcriptome variations. Recruitment drove the expansion of atrial macrophages; accordingly, inhibition of monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Deleting Spp1 established macrophage-derived osteopontin as a pleiotropic signal that promotes atrial fibrillation through pro-fibrotic, inflammatory crosstalk with an arsenal of local immune and stromal cells. Taken together, we identify SPP1+ macrophages as targets for immunomodulatory therapy in atrial fibrillation.
|
| |
|
| Overall design |
Single-cell mRNA sequencing was used to investigate the transcriptomic differences between non-cardiomyocytes FACS-purified from left atrial tissues collected from 2 C57BL/6 bone marrow transplanted (BMT) and 2 Spp1-/- BMT mice exposed to Hypertension, Obesity and Mitral valvE Regurgitation (HOMER).
|
| Web link |
https://www.science.org/doi/10.1126/science.abq3061
|
| |
|
| Contributor(s) |
Hulsmans M, Schloss MJ, Lee I, Naxerova K, Nahrendorf M |
| Citation(s) |
37440641, 39149373 |
| |
| Submission date |
Feb 09, 2023 |
| Last update date |
Sep 12, 2024 |
| Contact name |
I-Hsiu Lee |
| Organization name |
Mass General Hospital/Harvard University
|
| Department |
Center for Systems Biology
|
| Street address |
185 Cambridge Street
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02114 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE224959 |
The role of stromal and immune cells in atrial disease |
|
| Relations |
| BioProject |
PRJNA933166 |
Less...
More...