Abstract 13348: Single Nuclear RNA-seq of Human Thoracic Aortic Dissection Identifies Expansion of Vascular Smooth Muscle Cells With a Distinct Transcriptional Phenotype
| العنوان: | Abstract 13348: Single Nuclear RNA-seq of Human Thoracic Aortic Dissection Identifies Expansion of Vascular Smooth Muscle Cells With a Distinct Transcriptional Phenotype |
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| المؤلفون: | Shamsudheen Vellarikkal, Deepak Atri, Vivian Lee-Kim, Ankith Reddy, Tsuyoshi Kaneko, Hari R MALLIDI, Rakhshinda Rehman, Prem S Shekar, Laura E Fredenburgh, Oscar Sias-Garcia, J Daniel D Muehlschlegel, Rajat Gupta |
| المصدر: | Circulation. 144 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Physiology (medical), Cardiology and Cardiovascular Medicine |
| الوصف: | Introduction: Phenotypic switching of vascular cells is a complex process associated with vascular disorders, including thoracic aortic aneurysm (TAA). Vascular smooth muscle cells (VSMCs) appear to switch from a contractile to synthetic phenotype in TAA. Single nuclear RNA-seq (snRNA-seq) of normal human and TAA aortas may be used to characterize cell heterogeneity of normal aortas, population shifts in disease, and the transcriptional profile of VSMC phenotypic switching. Hypothesis: snRNA-seq of normal and TAA aortas will identify the cell heterogeneity and transcriptional profiles of TAA. Methods: We performed snRNA-seq of 5 aortas from 2 normal and 3 TAA patients. We used a 10X-CellBender pipeline for profiling and analysis. Results: snRNA-seq identified 6 major cell types. The majority were VSMCs, exhibiting 4 sub-populations in all specimens (a). Cell distribution comparisons showed VSMC1 (ELN, PKD1, FLNA high) and VSMC2 (PRKG1, PDE3A, PCDH7 high) to be differentially-enriched in controls and TAA samples, respectively (b,c). Gene set and trajectory analyses confirmed prior observations of phenotypic switching (d,e). Genes associated with switching in VSMCs included TAA genes (PRKG1, PKD1, FLNA) with concordance of expression and putative function of Mendelian variants (i-k). Cell junction and regulation of muscle contraction pathways drove trajectory. We further assessed cell-type heritability of vascular GWAS variants (h). These gene sets were differentially-regulated between control and TAA. The strongest association was between VSMC2 and ascending aortic size (h). Conclusions: In this study, we demonstrated a dissociation bias-free method for snRNA-Seq of human vasculature. We confirmed enrichment of synthetic VSMCs in TAA and implicate phenotypic switching as a pathologic mechanism. Our study identifies a cell type-specific transcriptional profile of aortopathy genes, which may drive TAA and represent therapeutic targets. |
| تدمد: | 1524-4539 0009-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c7c202920552d37d4568f7b0709fc6a1 https://doi.org/10.1161/circ.144.suppl_1.13348 |
| رقم الأكسشن: | edsair.doi...........c7c202920552d37d4568f7b0709fc6a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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