Abstract MP07: Multi Omic Atlas Of Human Coronary Artery Disease
| Autor: | Junedh M Amrute, Andrea Bredemeyer, Xin Luo, Tracy Yamawaki, Andrew Koenig, Cameran Jones, Simon Jackson, Milena B Furtado, Sally Shi, Chi-Ming Li, Brandon Ason, Nathan O Stitziel, Kory J Lavine |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 41 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Previous human genetic studies have provided insight into the genes and pathways involved in atherosclerotic CAD, however, there remains an incomplete understanding of the precise cell types that drive disease pathogenesis. To generate a cellular atlas for CAD, we performed CITE-seq on left human coronary arteries with obstructive CAD (n=5), CAD with coronary stenting (n=4), or controls without CAD (n=5); single-nuclei RNA sequencing was performed on a subset (n=4) of these samples. Standard histopathology was used to assess the degree of atherosclerotic plaque burden and annotate disease status (Fig b). Sequencing yielded 65,437 cells with 23 distinct cell types (Fig a) and canonical marker genes (Fig c). Within the stroma we found prominent transcriptional changes in endothelial cells and fibroblasts along with the emergence of a modulated smooth muscle cell (SMC) state in CAD tissue. The modulated SMC cells were enriched with fibroblast activator protein surface expression. Additionally, we noted the emergence of a proliferative SMC population in stented arteries. Two distinct fibroblast populations were present: one was specific to coronary arteries in GTEx and this population was enriched for SVEP1 expression in the CAD samples. Furthermore, pseudotime analysis and integration of published single-cell SMC lineage tracing data in atherosclerotic mice show that this population is SMC-derived. Within the immune cells, we find expansion of B- and T-cell populations with transcriptional changes within myeloid subsets. We found 4 distinct macrophage populations: inflammatory, TREM2, HLA-II high, and resident-like macrophages. CAD macrophages had enriched inflammatory and foam-cell like signatures compared to controls. Furthermore, foam cell genes were localized to the inflammatory and TREM2 macrophages. Together, our results provide the first multi-omic single cell atlas of human coronary artery tissue with insights into disease pathogenesis. |
| Databáze: | OpenAIRE |
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