A Second Heart Field-Derived Vasculogenic Niche Contributes to Cardiac Lymphatics

Ghislaine Lioux (1) , Xiaolei Liu (2) , Susana Temiño (1) , Michael Oxendine (3) , Estefanía Ayala (4) , Sagrario Ortega (4) , Robert G Kelly (5) , Guillermo Oliver (2) , Miguel Torres (1)

1 CNIC - Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain]
2 Northwestern University [Evanston]
3 Center for Vascular and Developmental Biology, Feinberg Cardiovascular and Renal Research Institute
4 CNIO - Spanish National Cancer Research Center
5 IBDM - Institut de Biologie du Développement de Marseille

The mammalian heart contains multiple cell types that appear progressively during embryonic development. Advances in determining cardiac lineage diversification has often been limited by the unreliability of genetic tracers. Here we combine clonal analysis, genetic lineage tracing, tissue transplantation and mutant characterization to investigate the lineage relationships between epicardium, arterial mesothelial cells (AMCs) and the coronary vasculature. We report a contribution of the second heart field (SHF) to a vasculogenic niche composed of AMCs and submesothelial cells at the base of the pulmonary artery. Sub-mesothelial cells from this niche differentiate into lymphatic endothelial cells and, in close association with AMC-derived cells, contribute to, and are essential for the development of ventral cardiac lymphatics. In addition, regionalized epicardial/mesothelial retinoic acid signaling regulates lymphangiogenesis, contributing to the niche properties. These results uncover a SHF vasculogenic contribution to coronary lymphatic development through a local niche at the base of the great arteries.

Mots clés: lymphatic endothelium; vasculogenesis; coronary vasculature; retinoic acid; clonal analysis; epicardium; mesothelium; pericardium; Islet1Cre

Domaines: Sciences du Vivant [q-bio]

Ghislaine Lioux, Xiaolei Liu, Susana Temiño, Michael Oxendine, Estefanía Ayala, et al.. A Second Heart Field-Derived Vasculogenic Niche Contributes to Cardiac Lymphatics. Developmental Cell, 2020, 52, pp.350 - 363.e6. ⟨10.1016/j.devcel.2019.12.006⟩. ⟨hal-03141943⟩