Single-nuclei multiomic analyses identify human cardiac lymphatic endothelial cells associated with coronary arteries in the epicardium

• Published in: Cell reports (Cambridge) 2023-09, Vol.42 (9), p.113106-113106, Article 113106
• Main Authors: Travisano, Stanislao Igor, Harrison, Michael R.M., Thornton, Matthew E., Grubbs, Brendan H., Quertermous, Thomas, Lien, Ching-Ling
• Format: Article
• Language: English
• Subjects: CP: Cell biology; CP: Developmental biology; human fetal heart, cardiac lymphatic progenitors, multiome, PROX1, ETV2
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113106

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. [Display omitted] •Single-nuclei multiomic analyses of human fetal heart reveal cardiac LECs in epicardium•Cardiac lymphatic vessels are mainly associated with coronary arteries•Human fetal cardiac LECs express PROX1 and RELN•ETV2 binding motif is enriched in human fetal cardiac LECs Travisano et al. integrate analyses of transcriptomics and the chromatin landscape of cardiac lymphatics of human fetal hearts. Cardiac lymphatic endothelial cells (LECs) are in the epicardium and associate preferentially with coronary arteries. These human fetal cardiac LECs show high PROX1 and RELN expression and have enriched ETV2 binding motifs.