Project description:We reported the transcriptional profiling of tdTomato-labeled c-Kit lineage cells in a mouse model of transplant arteriosclerosis by single-cell RNA sequencing.
Project description:We have applied single cell RNA sequencing (scRNA-seq) as an unbiased transcriptomics to characterize aortic immune cells in atherosclerosis. The scRNA-seq analysis revealed macrophage heterogeneity at the single-cell level in mouse atherosclerotic aorta.
Project description:We generated a novel genetic mouse model of fatal aortic dissection by introducing a pathogenic variant of Fbn1 (Fbn1G234D/G234D), identified in a patient with familial aortic dissection, into mice using the CRISPR/Cas9 system. To investigate the cellular heterogeneity underlying the progression of aortic dissection, we performed single cell RNA sequencing on aortic tissues obtained from Fbn1G234D/G234D (AD) and wild-type mice (WT).
Project description:Although abnormal TGFbeta signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, the precise role of TGFbeta signaling in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to investigate the role of TGFbeta signaling in molecular pathways of pathogenesis associated with development of aortic aneurysm and aortic rupture. This study reports an isoform-specific effect of TGFbeta in MFS aortic disease and the effects of deleting the first hybrid domain of fibrillin-1 on TGFbeta signaling. Distinct molecular differences in mouse models of aneurysm (Fbn_GT-8_plus), of aneurysm and rupture (Fbn1_GT-8_H1delta), and of microdissection (Fbn1_H1delta_plus) were identified, which associated with TGFbeta signaling and extracellular matrix composition, possibly contributing to the development of dissection and rupture. These findings offer new insights into the pathophysiological mechanisms that potentially drive initiation of aortic dissection and could pave the way for development of new treatment targets of aortic disease.