Development of the Cardiovascular System in Embryoid Bodies Derived from Embryonic Stem Cells
Development of the Cardiovascular System in Embryoid Bodies Derived from Embryonic Stem Cells
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胚胎干细胞衍生的胚体中心血管系统的发育
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
J. Hescheler
中科院分区：
文献类型：
--
作者：
H. Sauer;M. Wartenberg;A. Sachinidis;J. Hescheler
脊椎动物的心脏和循环系统是第一个从胚状体细胞发育而来的胚胎器官。了解这是如何发生的，已通过使用报告基因的心脏和内皮细胞特异性启动子控制下的绿色荧光蛋白的表达进行了检查。心脏原基可以被认为是源自侧板中胚层的间充质细胞的双侧对称股，其形成由细胞外基质（心脏胶质）分隔的单独的心肌层和内膜层。内胚层来源于原肠胚形成期间的侵入细胞，并提供影响相邻中胚层的信号（因子如骨形态发生蛋白-2（BMP-2）、成纤维细胞生长因子-1，2，4（FGF-1，2，4））。内皮细胞又受到转化生长因子-β和血管内皮生长因子（VEGF）的影响。其他因子如心肌营养素-1和白血病抑制因子也控制心脏发育。首先是一个简单的线性心管，它继续形成模块化元件（心房，心室，隔膜和瓣膜）。通过自身折叠和融合，形成了四室心脏。这些结构事件由特定的信号分子触发，并涉及与特定类型的离子通道相关的活性氧和特征性动作电位，以及编码心房利钠因子和肌节蛋白的心脏特异性基因的发育控制表达模式（即，α-和β-心肌肌球蛋白重链、肌球蛋白轻链亚型2 V、肌联蛋白[Z盘]、肌联蛋白[M带]、α-辅肌动蛋白、肌节蛋白、肌节α-肌动蛋白和肌钙蛋白T），随后是M蛋白。然而，在早期胚胎干细胞（ES）衍生的心肌细胞细胞收缩是由细胞内Ca 2+储存引起的Ca 2+瞬变触发的，终末分化的心肌细胞的收缩依赖于诱发的动作电位，导致心肌细胞“跳动”前几天出现的L型电压依赖性Ca 2+通道的开放。胚胎的血管结构从近轴和侧板中胚层以及卵黄囊胚外中胚层中的成血管细胞发育而来，在那里它们形成血岛的外层。血管发生和血管生成是通过缺氧诱导因子-1受到组织细胞周围氧分压的严格调节。参与心血管分化的许多基因直接或间接受缺氧调节，VEGF是血管发生所需的主要因子。如果我们知道如何将胚胎干细胞引导到心血管或其他器官系统的特定细胞谱系，那么胚胎干细胞的治疗用途将大大提高。
The vertebrate heart and circulatory system is the first embryonic organ to develop from cells in the embryoid body. Understanding how this happens has been examined through the use of reporter genes by expression of green fluorescent protein under the control of cardiac- and endothelial cell—specific promoters. The cardiac primordial may be recognized as bilaterally symmetric strands of mesenchymal cells derived from the lateral plate mesoderm, which forms separate layers of myocardium and endocardium separated by extracellular matrix (cardiac jelly). The endoderm derives from ingressing cells during gastrulation and provides signals (factors such as bone morphogenetic protein-2 (BMP-2), fibroblast growth factor-1,2,4 (FGF-1,2,4)) that influence the adjacent mesoderm. The endocardium is in turn influenced by transforming growth factor-β and vascular endothelial growth factor (VEGF). Other factors such as cardiotrophin-1 and leukemia inhibitory factor also control cardiac development. First there is a simple linear heart tube, which goes on to form modular elements (atria, ventricles, septa, and valves). By folding on itself and fusing, the four-chambered heart is formed. These structural events are triggered by specific signaling molecules and involve reactive oxygen species and characteristic action potentials correlated with specialized types of ion channels, as well as a developmentally controlled expression pattern of the cardiac-specific genes encoding atrial natriuretic factor and sarcomeric proteins (i.e., α- and β-cardiac myosin heavy chain, myosin light chain isoform 2V, titin [Z-disk], titin [M-band], a-actinin, myomesin, sarcomeric a-actin, and troponin T), followed by M-protein. Whereas in early stage embryonic stem (ES) cell—derived cardiomyocytes cell contraction is triggered by Ca2+ transients arising from intracellular Ca2+ stores, contraction of terminally differentiated cardiac cells is dependent on an evoked action potential leading to opening of L-type voltage-dependent Ca2+ channels that appear several days before “beating” of cardiomyocytes. The vascular structures of the embryo develop from angioblasts in the paraaxial and lateral plate mesoderm as well as in the yolk sac extraembryonic mesoderm, where they form the outer layer of blood islands. Vasculogenesis and angiogenesis are strictly regulated by the pericellular oxygen tension of the tissue through hypoxia inducible factor-1. Many of the genes involved in cardiovascular differentiation are directly or indirectly regulated by hypoxia, with VEGF being a principle factor required for vasculogenesis. Therapeutic use of ES cells would be greatly enhanced if we knew how to direct ES cells to specific cell lineages in the cardiovascular or other organ systems.
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影响因子：
2.7
作者：
Kotch, LE;Iyer, NV;Semenza, GL
通讯作者：
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15.9
作者：
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20.3
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56.9
作者：
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影响因子：
10.5
作者：
Iyer, NV;Kotch, LE;Semenza, GL
通讯作者：
Semenza, GL