ArticleCirculation2020
Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis.
Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers, 3 of them syntheses that pooled it.
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Who cites it
275 citing papers in PubMed, 3 syntheses or guidelines pooled it, 371 citations in OpenAlex.
- Comprehensive Integration of Multiple Single-Cell Transcriptomic Data Sets Defines Distinct Cell Populations and Their Phenotypic Changes in Murine Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.Cell reports · 2023Pooled it
- FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.Circulation research · 2023Pooled it
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Smooth Muscle Cell Plasticity as a Central Determinant of Plaque Stability.Current atherosclerosis reports · 2026Review
- Loss of the Coronary Artery Disease Risk GeneCirculation · 2026Article
- Dual Lineage Tracing Identifies Cellular Mechanisms Underlying Radiation-Associated Changes in Atherosclerotic Lesion Composition-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Metabolic control of smooth muscle cell phenotype switching in atherosclerosis.Science advances · 2026Article
- tRNA-derived small RNAs in vascular smooth muscle cell phenotypic switching and vascular remodelling.Molecular biology reports · 2026Review
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis.bioRxiv : the preprint server for biology · 2026Article
- Lineage tracing from cellular heritage to disease destiny.Nature genetics · 2026Review
- Immunothrombotic Cell-Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology.International journal of molecular sciences · 2026Review
- Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses.Genes · 2026Review
- Smooth Muscle Cell Cytoglobin is a Negative Regulator of Atherosclerotic Fibrous Cap Development.bioRxiv : the preprint server for biology · 2026Article
- Article
- Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC.Circulation research · 2026Article
- miR-146a-5p mediates atherogenic signalling from immune to vascular cells.Cardiovascular research · 2026Article
- The Complex Role of Methylation in Regulating Vascular Smooth Muscle Cell Phenotypic States in Vascular Remodeling and Atherosclerosis.Biomolecules · 2026Review
- Inflammatory Neovascularization and Vascular Remodeling Associated With Carotid Plaque Destabilization.CNS neuroscience & therapeutics · 2026Article
215 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundRupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability.
methodsWe conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis.
resultsWe provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11
conclusionsTaken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3
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