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Updated: Jul 26, 2026
Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration
Published on: March 18, 2016
Single-nuclei multiomic analyses identify human cardiac lymphatic endothelial cells associated with coronary arteries
Stanislao Igor Travisano1, Michael R M Harrison2, Matthew E Thornton3
1The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Insights
Researchers characterized human fetal heart lymphatic endothelial cells (LECs), revealing their unique molecular markers and association with coronary arteries. This study offers insights into cardiac lymphatic development and function.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Molecular Biology
Background:
- Cardiac lymphatic vessels are crucial for heart fluid balance, inflammation, and repair.
- Their development in human fetuses mirrors patterns seen in zebrafish, showing close ties to coronary arteries.
Purpose of the Study:
- To molecularly characterize cardiac lymphatic endothelial cells (LECs) in the developing human fetal heart.
- To understand the heterogeneity and plasticity of the cardiac endothelium.
- To identify molecular drivers for the arterial association of cardiac lymphatics.
Main Methods:
- Single-nuclei multiomic analysis of human fetal heart tissue.
- Cell-type-specific integrative analysis.
- In vivo molecular characterization.
Main Results:
- Identified a distinct population of cardiac LECs residing in the epicardium.
- Revealed plasticity and heterogeneity within the cardiac endothelium.
- Found high VEGFC expression in arterial endothelial cells and epicardium-derived cells, supporting arterial association.
- Characterized cardiac LECs by PROX1, RELN, and ETV transcription factor enrichment.
Conclusions:
- This study provides the first in vivo molecular characterization of human cardiac lymphatics.
- The findings offer a valuable resource for understanding fetal heart development and lymphatic function.
- Identified key molecular players, including VEGFC and specific transcription factors, involved in cardiac lymphatic development.
Abstract:
Cardiac lymphatic vessels play important roles in fluid homeostasis, inflammation, disease, and regeneration of the heart. The developing cardiac lymphatics in human fetal hearts are closely associated with coronary arteries, similar to those in zebrafish hearts. We identify a population of cardiac lymphatic endothelial cells (LECs) that reside in the epicardium. Single-nuclei multiomic analysis of the human fetal heart reveals the plasticity and heterogeneity of the cardiac endothelium. Furthermore, we find that VEGFC is highly expressed in arterial endothelial cells and epicardium-derived cells, providing a molecular basis for the arterial association of cardiac lymphatic development. Using a cell-type-specific integrative analysis, we identify a population of cardiac lymphatic endothelial cells marked by the PROX1 and the lymphangiocrine RELN and enriched in binding motifs of erythroblast transformation specific (ETS) variant (ETV) transcription factors. We report the in vivo molecular characterization of human cardiac lymphatics and provide a valuable resource to understand fetal heart development.
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