ArticleCirculation research2018
Topological Arrangement of Cardiac Fibroblasts Regulates Cellular Plasticity.
Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023Pooled it
- Type V collagen from macrophages regulates initial collagen assembly and alignment in post-infarcted hearts.NPJ Regenerative medicine · 2025Article
- Long QT syndrome type 3 gain-of-function of NaCommunications biology · 2025Article
- Review
- Sall4 and Gata4 induce cardiac fibroblast transition towards a partially multipotent state with cardiogenic potential.Scientific reports · 2024Article
- High-Speed Clearing and High-Resolution Staining for Analysis of Various Markers for Neurons and Vessels.Tissue engineering and regenerative medicine · 2024Article
- Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals.Pharmaceutics · 2024Review
- Cardiac fibroblasts and mechanosensation in heart development, health and disease.Nature reviews. Cardiology · 2023Review
- The Current Therapeutic Role of Chromatin Remodeling for the Prognosis and Treatment of Heart Failure.Biomedicines · 2023Review
- Review
- Progress on role of ion channels of cardiac fibroblasts in fibrosis.Frontiers in physiology · 2023Review
- Functions of exogenous FGF signals in regulation of fibroblast to myofibroblast differentiation and extracellular matrix protein expression.Open biology · 2022Review
- Disruption of the circadian clock drivesScience advances · 2022Article
- How Chromatin Stiffens Fibroblasts.Current opinion in physiology · 2022Article
- Cardiac Fibrosis and Fibroblasts.Cells · 2021Review
- Recent Advances in Single-Cell Profiling and Multispecific Therapeutics: Paving the Way for a New Era of Precision Medicine Targeting Cardiac Fibroblasts.Current cardiology reports · 2021Review
- Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering.Micromachines · 2021Review
- Pathological matrix stiffness promotes cardiac fibroblast differentiation through the POU2F1 signaling pathway.Science China. Life sciences · 2021Article
- Engineering the Cellular Microenvironment of Post-infarct Myocardium on a Chip.Frontiers in cardiovascular medicine · 2021Review
- Effect of Substrate Stiffness on Physicochemical Properties of Normal and Fibrotic Lung Fibroblasts.Materials (Basel, Switzerland) · 2020Article
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16 authors at 5 institutions in 4 countries.
Funding
Abstract
rationaleCardiac fibroblasts do not form a syncytium but reside in the interstitium between myocytes. This topological relationship between fibroblasts and myocytes is maintained throughout postnatal life until an acute myocardial injury occurs, when fibroblasts are recruited to, proliferate and aggregate in the region of myocyte necrosis. The accumulation or aggregation of fibroblasts in the area of injury thus represents a unique event in the life cycle of the fibroblast, but little is known about how changes in the topological arrangement of fibroblasts after cardiac injury affect fibroblast function.
objectiveThe objective of the study was to investigate how changes in topological states of cardiac fibroblasts (such as after cardiac injury) affect cellular phenotype. METHODS AND
resultsUsing 2 and 3-dimensional (2D versus 3D) culture conditions, we show that simple aggregation of cardiac fibroblasts is sufficient by itself to induce genome-wide changes in gene expression and chromatin remodeling. Remarkably, gene expression changes are reversible after the transition from a 3D back to 2D state demonstrating a topological regulation of cellular plasticity. Genes induced by fibroblast aggregation are strongly associated and predictive of adverse cardiac outcomes and remodeling in mouse models of cardiac hypertrophy and failure. Using solvent-based tissue clearing techniques to create optically transparent cardiac scar tissue, we show that fibroblasts in the region of dense scar tissue express markers that are induced by fibroblasts in the 3D conformation. Finally, using live cell interferometry, a quantitative phase microscopy technique to detect absolute changes in single cell biomass, we demonstrate that conditioned medium collected from fibroblasts in 3D conformation compared with that from a 2D state significantly increases cardiomyocyte cell hypertrophy.
conclusionsTaken together, these findings demonstrate that simple topological changes in cardiac fibroblast organization are sufficient to induce chromatin remodeling and global changes in gene expression with potential functional consequences for the healing heart.
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