GSE224947 The role of stromal and immune cells in atrial disease [II]

Contributors : Maarten Hulsmans ; Maximilian J Schloss ; I-Hsiu Lee ; Kamila Naxerova ; Matthias NahrendorfSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusIn 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 throu...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research