ArticleScience translational medicine2024
Single-cell multiomics guided mechanistic understanding of Fontan-associated liver disease.
Article in Science translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 17 citations in OpenAlex.
- YAP1 induces hepatocellular carcinoma via DNA demethylation rather than by canonical driver gene mutations.Communications biology · 2026Article
- Proteomic Remodeling in Fontan Circulation Associated with Fibrosis and Time-Dependent Immune-Metabolic Alteration.International journal of molecular sciences · 2026Article
- Single-cell spatial transcriptomics reveals hepatocyte reprogramming in Fontan-associated liver disease.JCI insight · 2026Article
- Pulmonary arterial hypertension induces a metabolic and inflammatory hepatopathy.The Journal of clinical investigation · 2026Article
- A Dynamic 3D Human Liver Sinusoid Model for Mechanistic Interrogation of Fontan-Associated Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pulmonary Arterial Hypertension Induces a Metabolic and Inflammatory Hepatopathy.bioRxiv : the preprint server for biology · 2026Article
- Prognostic biomarkers in Fontan associated liver disease.Translational pediatrics · 2026Review
- A second-hit conceptual framework for pulmonary arterial hypertension in adult congenital heart disease: genetics, hemodynamics, and treat-and-repair.Frontiers in cardiovascular medicine · 2026Review
- Partial restoration of mitochondrial dysfunction by AAV-Ant1 protects from dilated cardiomyopathy in Ant1Nature communications · 2025Article
- Activin B Regulates Fibroblasts to Promote Granulation Tissue Formation and Angiogenesis During Murine Skin-Wound Healing via the JNK/ERK Signaling Pathway.International journal of molecular sciences · 2025Article
- Obstetric complications in pregnant people with Fontan circulation: Identifying candidate pathologic pathways in the placenta.Pregnancy (Hoboken, N.J.) · 2025Article
- The Cardiohepatic Axis in Heart Failure.JACC. Basic to translational science · 2025Review
- Overcoming borders: International cooperation in re-use and re-interpretation of omics data in Fontan circulation.International journal of cardiology. Congenital heart disease · 2025Article
- Biliary Metaplasia and Macrophage Activation Define the Cellular Landscape of Cardiogenic Liver Disease.JACC. Basic to translational science · 2025Article
- Cellular mechanical memory: a potential tool for mesenchymal stem cell-based therapy.Stem cell research & therapy · 2025Review
- Comprehensive Multiomic Analysis Reveals Metabolic Reprogramming Underlying Human Fontan-Associated Liver Disease.Journal of the American Heart Association · 2025Article
- Novel immunologic mechanisms for Fontan-associated liver disease.International journal of cardiology. Congenital heart disease · 2025Article
- Fontan-Associated Liver Disease.Seminars in liver disease · 2025Review
- A single-cell multiomics profile of Fontan-associated liver disease.Nature reviews. Gastroenterology & hepatology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Individuals with a Fontan circulation (FC) exhibit central venous hypertension and face life-threatening complications of hepatic fibrosis, known as Fontan-associated liver disease (FALD). The fundamental biology and mechanisms of FALD are little understood. Here, we generated a transcriptomic and epigenomic atlas of human FALD at single-cell resolution using multiomic snRNA-ATAC-seq. We found profound cell type-specific transcriptomic and epigenomic changes in FC livers. Central hepatocytes (cHep) exhibited the most substantial changes, featuring profound metabolic reprogramming. These cHep changes preceded substantial activation of hepatic stellate cells and liver fibrosis, suggesting cHep as a potential first "responder" in the pathogenesis of FALD. We also identified a network of ligand-receptor pairs that transmit signals from cHep to hepatic stellate cells, which may promote their activation and liver fibrosis. We further experimentally demonstrated that activins A and B promote fibrotic activation in vitro and identified mechanisms of activin A's transcriptional activation in FALD. Together, our single-cell transcriptomic and epigenomic atlas revealed mechanistic insights into the pathogenesis of FALD and may aid identification of potential therapeutic targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.