Coronary arteries form by developmental reprogramming of venous cells.
Coronary arteries form by developmental reprogramming of venous cells.
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作者：
冠状动脉为心脏提供氧气和营养，冠状动脉疾病是导致死亡的主要原因。阐明冠状动脉发育的程序可以帮助理解疾病并导致新的治疗方法，但该过程的许多方面，包括其发育起源，仍然不清楚。目前的模型认为冠状动脉是由心外膜（一种覆盖并促进心脏发育的组织）中的祖细胞重新组装内皮管形成的。在这里，我们使用小鼠的组织学和克隆分析，以及心脏器官培养，表明冠状动脉血管来自静脉窦的血管生成芽，静脉窦是将循环血液返回胚胎心脏的主要静脉。发芽的静脉内皮细胞在迁移和侵入心肌时去分化。侵入的细胞分化成动脉和毛细血管，而留在表面的细胞再分化成静脉。这些结果表明，一些分化的静脉细胞保持发育可塑性，并表明位置特异性心脏信号触发其去分化和转化为冠状动脉，毛细血管和静脉。了解这种新的发育重编程过程和识别内源性信号应该建议更自然的方式工程冠状动脉旁路移植术和心脏血管重建。
Coronary arteries supply the heart with oxygen and nutrients, and coronary artery disease is the leading cause of death. Elucidating the program of coronary artery development could aid understanding of the disease and lead to new treatments, but many aspects of the process, including their developmental origin, remain obscure. Current models posit that coronary arteries form by de novo assembly of endothelial tubes from progenitor cells in the proepicardium, a tissue that spreads over and contributes to the developing heart. Here, we use histological and clonal analysis in mice, and cardiac organ culture, to show that coronary vessels arise instead from angiogenic sprouts of the sinus venosus, the major vein that returns circulating blood to the embryonic heart. Sprouting venous endothelial cells dedifferentiate as they migrate over and invade the myocardium. Invading cells differentiate into arteries and capillaries, whereas cells remaining on the surface redifferentiate into veins. These results show that some differentiated venous cells retain developmental plasticity, and suggest that position-specific cardiac signals trigger their dedifferentiation and conversion into coronary arteries, capillaries, and veins. Understanding this novel developmental reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart.
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影响因子：
2.5
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