Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries.
Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries.
复制标题
心外膜下内皮细胞侵入胚胎心室壁形成冠状动脉
作者：
冠状动脉将血液输送到心肌。了解冠状动脉的发育程序为冠状动脉疾病的治疗提供了见解。多个来源被描述为对冠状动脉有贡献，包括心外膜、静脉窦（SV）和内膜。然而，冠状血管的发育起源仍在紧张的研究中。我们已经产生了一种新的遗传工具，用于研究冠状动脉的发展，一个AplnCreER小鼠系，表达诱导型Cre重组酶，特别是在发展中的冠状动脉血管。冠状动脉发育的定量分析和AplnCreER命运追踪的定时诱导表明，心外膜下内皮细胞（EC）的后代既侵入致密心肌形成冠状动脉，又保留在表面上产生静脉。我们发现这些心外膜下的内皮细胞是发育中心脏心肌内冠状血管的主要来源。体外外植体试验表明，这些心外膜下EC大多数来自SV和心房的内膜，而不是心室内膜。Apln阳性细胞的克隆分析表明，一个单一的subepicardial EC同样有助于冠状动脉和静脉。总的来说，这些数据表明，心外膜下EC是心室壁心肌内冠状动脉的主要来源，并且冠状动脉和静脉在发育中的心脏中具有共同的起源。
Coronary arteries bring blood flow to the heart muscle. Understanding the developmental program of the coronary arteries provides insights into the treatment of coronary artery diseases. Multiple sources have been described as contributing to coronary arteries including the proepicardium, sinus venosus (SV), and endocardium. However, the developmental origins of coronary vessels are still under intense study. We have produced a new genetic tool for studying coronary development, an AplnCreER mouse line, which expresses an inducible Cre recombinase specifically in developing coronary vessels. Quantitative analysis of coronary development and timed induction of AplnCreER fate tracing showed that the progenies of subepicardial endothelial cells (ECs) both invade the compact myocardium to form coronary arteries and remain on the surface to produce veins. We found that these subepicardial ECs are the major sources of intramyocardial coronary vessels in the developing heart. In vitro explant assays indicate that the majority of these subepicardial ECs arise from endocardium of the SV and atrium, but not from ventricular endocardium. Clonal analysis of Apln-positive cells indicates that a single subepicardial EC contributes equally to both coronary arteries and veins. Collectively, these data suggested that subepicardial ECs are the major source of intramyocardial coronary arteries in the ventricle wall, and that coronary arteries and veins have a common origin in the developing heart.
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