RETROVIRAL ANALYSIS OF CARDIAC MORPHOGENESIS - DISCONTINUOUS FORMATION OF CORONARY VESSELS
RETROVIRAL ANALYSIS OF CARDIAC MORPHOGENESIS - DISCONTINUOUS FORMATION OF CORONARY VESSELS
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DOI：
10.1073/pnas.89.20.9504
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
FISCHMAN, DA
中科院分区：
文献类型：
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作者：
MIKAWA, T;FISCHMAN, DA
冠状血管系统的细胞祖细胞被认为在蛋孵育的第17和27阶段（第3-5天）之间的心外膜形态发生期间进入鸡心脏。为了追踪引起体内冠状动脉的细胞，我们应用逆转录病毒细胞标记程序并分析了孵化后鸡心脏中血管平滑肌、内皮和结缔组织的克隆群体。我们的数据提供了直接的证据，即（i）血管平滑肌祖细胞开始进入心脏在第17阶段，基本上在心脏开始推进性收缩之后;（ii）心肌细胞、血管平滑肌、血管周围成纤维细胞和冠状动脉内皮细胞在这些细胞迁移到心脏时都来源于独立的前体细胞;（iii）冠状血管的内皮细胞具有与内皮细胞不同的克隆起源;（iv）冠状动脉通过不连续集落的聚结形成（即，原位血管发生），每一种来源于在注射逆转录病毒时标记的创始细胞（阶段17-18）;和（v）冠状动脉含有由“多克隆”组成的离散节段。“这些研究表明，通过使用重组逆转录病毒将基因靶向冠状动脉祖细胞的可行性。
Cellular progenitors of the coronary vasculature are believed to enter the chicken heart during epicardial morphogenesis between stages 17 and 27 (days 3-5) of egg incubation. To trace cells which give rise to the coronary arteries in vivo, we applied retroviral cell tagging procedures and analyzed clonal populations of vascular smooth muscle, endothelium, and connective tissue in the hearts of post-hatch chickens. Our data provide direct proof that (i) vascular smooth muscle progenitors begin to enter the heart at stage 17, substantially after the heart begins propulsive contractions; (ii) cardiac myocytes, vascular smooth muscle, perivascular fibroblasts, and coronary endothelial cells all derive from independent precursors when these cells migrate into the heart; (iii) endothelial cells of the coronary vessels have a different clonal origin than endothelial cells of the endocardium; (iv) coronary arteries form by the coalescence of discontinuous colonies (i.e., in situ vasculogenesis), each derived from a founder cell tagged at the time of retroviral injection (stages 17-18); and (v) coronary arteries contain discrete segments composed of "polyclones." These studies indicate the feasibility of gene targeting to coronary progenitors through the use of recombinant retroviruses.