冠状动脉起源和发育机制的研究

Cardiovascular diseases are the leading cause of death globally. Despite the medical importance of coronary arteries, their embryonic origins and developmental mechanisms remain unclear. There is still ongoing debate regarding the cellular origin and tissue sources for the coronary vasculature. The proepicardium, sinus venosus, and endocardium were considered as potential sources of coronary. To address the coronary origin, we have generated a new genetic tool for studying the coronary development, an AplnCreER knock-in mouse line. We could genetically label subepicardial ehdothelial cells by AplnCreER. By lineage tracing of these subepicardial ehdothelial cells and their descendants, we could observe if they migrate into the compact myocardium to form coronary arteries. Using clonal analysis based on Confetti multicolor reporter system, we aim to detect that whether single subepicardial ehdothelial cell gives rise to both coronary arteries and veins. Furthermore, lineage tracing experiments with Cre expressing mouse lines that label proepicardial or endocardial cells will reveal wheather proepicardial or endocardial cells contribute to coronary arteries in myocardium. The present study would not only help us to better understand the origin and developmental program of coronary vessel, but also provide new insight for the field of cardiovascular regenerative medicine.

心血管疾病是全世界死亡的首要原因。尽管冠状动脉在医学上具有重要意义，人们对冠状动脉的胚胎起源和发育机制尚未全面了解。关于冠状动脉血管的细胞起源和组织来源问题仍在不断地争论。目前认为前体心外膜、静脉窦和心内膜作为冠状动脉潜在的来源。为了解析冠状动脉的起源问题，我们构建了用于研究冠状动脉发育的新的遗传工具，AplnCreER基因敲入小鼠。利用AplnCreER小鼠遗传标记心外膜下内皮细胞。通过谱系示踪观察心外膜下内皮细胞及其子代细胞是否迁移到致密心肌层中形成冠状动脉。利用 Confetti多彩报告基因系统的克隆分析，检测单个心外膜下内皮细胞是否是冠状动脉和静脉共同的起源。运用标记前体心外膜或心内膜细胞的Cre小鼠的谱系示踪实验，将会揭示前体心外膜或心内膜细胞是否对心肌冠状动脉有贡献。本项研究将有助于我们更好地了解冠状动脉的起源和发育过程，为心血管再生医学领域提供新的思路。

心血管疾病是全世界死亡的首要原因。尽管冠状动脉在医学上具有重要意义，人们对冠状动脉的胚胎起源和发育机制尚未全面了解。关于冠状动脉血管的细胞起源和组织来源问题仍在不断地争论。近期的研究认为前体心外膜、静脉窦和心内膜作为冠状动脉潜在的来源。为了解析冠状动脉的起源问题，我们构建了用于研究冠状动脉发育的新的遗传工具，AplnCreER基因敲入小鼠。利用AplnCreER小鼠遗传标记心外膜下内皮细胞。通过谱系示踪发现胚胎期心肌内冠状动脉内皮细胞绝大多数来源于心内膜下内皮细胞。单个心外膜下内皮细胞是冠状动脉和静脉共同的起源。心内膜内皮细胞对冠状动脉内皮细胞也有贡献。本项目的研究有助于我们更好地了解冠状动脉的起源和发育过程，为心血管再生医学领域提供了新的思路。