Single-nuclei multiomic analyses identify human cardiac lymphatic endothelial cells associated with coronary arteries in the epicardium
Stanislao Igor Travisano,
Michael R.M. Harrison,
Matthew E. Thornton,
Brendan H. Grubbs,
Thomas Quertermous,
Ching-Ling Lien
Affiliations
Stanislao Igor Travisano
The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA; Corresponding author
Michael R.M. Harrison
The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA; Cardiovascular Research Institute, Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10021, USA
Matthew E. Thornton
Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Brendan H. Grubbs
Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Thomas Quertermous
Division of Cardiovascular Medicine and the Cardiovascular Institute, School of Medicine, Stanford University, Falk CVRC, Stanford, CA 94305, USA
Ching-Ling Lien
The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA; Departments of Surgery, Biochemistry, and Molecular Medicine, Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Summary: 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.
