Endocardium Minimally Contributes to Coronary Endothelium in the Embryonic Ventricular Free Walls. Issue 12 (10th June 2016)

• Record Type: Journal Article
• Authors: Zhang, Hui; Pu, Wenjuan; Li, Guang; Huang, Xiuzhen; He, Lingjuan; Tian, Xueying; Liu, Qiaozhen; Zhang, Libo; Wu, Sean M.; Sucov, Henry M.; Zhou, Bin
• Is Part Of: Circulation research. Volume 118:Issue 12(2016)
• Publication Date: 2016-06-10
• Subjects: blood vessel -- coronary -- coronary artery -- coronary development -- coronary origin -- lineage tracing; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.308749
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Rationale: : There is persistent uncertainty regarding the developmental origins of coronary vessels, with 2 principal sources suggested as ventricular endocardium or sinus venosus (SV). These 2 proposed origins implicate fundamentally distinct mechanisms of vessel formation. Resolution of this controversy is critical for deciphering the programs that result in the formation of coronary vessels and has implications for research on therapeutic angiogenesis. Objective: : To resolve the controversy over the developmental origin of coronary vessels. Methods and Results: : We first generated nuclear factor of activated T cells (Nfatc1)-Cre and Nfatc1-Dre lineage tracers for endocardium labeling. We found that Nfatc1 recombinases also label a significant portion of SV endothelial cells in addition to endocardium. Therefore, restricted endocardial lineage tracing requires a specific marker that distinguishes endocardium from SV. By single-cell gene expression analysis, we identified a novel endocardial gene natriuretic peptide receptor 3 (Npr3). Npr3 is expressed in the entirety of the endocardium but not in the SV. Genetic lineage tracing based on Npr3-CreER showed that endocardium contributes to a minority of coronary vessels in the free walls of embryonic heart. Intersectional genetic lineage tracing experiments demonstrated that endocardium minimally contributes to coronary endothelium in the embryonic ventricular free walls. Conclusions: : Our study suggested that SV, but not endocardium, is the major origin for coronary endothelium in the embryonic ventricular free walls. This work thus resolves the recent controversy over the developmental origin of coronary endothelium, providing the basis for studying coronary vessel formation and regeneration after injury. Abstract : Supplemental Digital Content is available in the text.