Biology subjects

Travisano, S. I.

Publications and source records attributed to Travisano, S. I..

2 recordsLinked to original sources

bioRxiv2023

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

SummaryCardiac 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 identified a population of cardiac lymphatic endothelial cells that reside in the epicardium. Single nuclei multiomic analysis of the human fetal heart revealed the plasticity and heterogeneity of the cardiac endothelium. Furthermore, we found that VEGFC is highly expressed in arterial endothelial cells, providing a molecular basis for the arterial association of cardiac lymphatic development. Using a cell-type-specific integrative analysis, we identified a novel population of cardiac lymphatic endothelial cells marked by the PROX1, the lymphangiocrine RELN, and enriched in binding motifs of ETV transcriptional factors. We report the first in vivo molecular characterization of human cardiac lymphatics and provide a valuable resource to understand fetal heart development.

developmental biology↗

bioRxiv2019

Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade

Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase MFng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade.

developmental biology↗