Single-Cell Transcriptomic Profiling of Vascular Smooth Muscle Cell Phenotype Modulation in Marfan Syndrome Aortic Aneurysm.

Arteriosclerosis, Thrombosis, and Vascular Biology
Albert J PedrozaMichael P Fischbein

Abstract

To delineate temporal and spatial dynamics of vascular smooth muscle cell (SMC) transcriptomic changes during aortic aneurysm development in Marfan syndrome (MFS). Approach and Results: We performed single-cell RNA sequencing to study aortic root/ascending aneurysm tissue from Fbn1C1041G/+ (MFS) mice and healthy controls, identifying all aortic cell types. A distinct cluster of transcriptomically modulated SMCs (modSMCs) was identified in adult Fbn1C1041G/+ mouse aortic aneurysm tissue only. Comparison with atherosclerotic aortic data (ApoE-/- mice) revealed similar patterns of SMC modulation but identified an MFS-specific gene signature, including plasminogen activator inhibitor-1 (Serpine1) and Kruppel-like factor 4 (Klf4). We identified 481 differentially expressed genes between modSMC and SMC subsets; functional annotation highlighted extracellular matrix modulation, collagen synthesis, adhesion, and proliferation. Pseudotime trajectory analysis of Fbn1C1041G/+ SMC/modSMC transcriptomes identified genes activated differentially throughout the course of phenotype modulation. While modSMCs were not present in young Fbn1C1041G/+ mouse aortas despite small aortic aneurysm, multiple early modSMCs marker genes were enriched, sugg...Continue Reading

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Citations

Jan 31, 2021·Genes·Tyler J CreamerElena Gallo MacFarlane
Feb 26, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhan HuJiangping Song
Mar 18, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Vikram JoshiArthur Beyder
Jun 29, 2021·Frontiers in Cardiovascular Medicine·Mengxia Fu, Jiangping Song
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Aug 7, 2021·Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists·Huan XuYong Wang
Sep 3, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Carmen YapVivian de Waard
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Oct 8, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Yanming LiYing H Shen

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