Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions

Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions
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DOI:
10.1161/01.res.82.10.1043
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发表时间:
1998-06-01
影响因子:
20.1
通讯作者:
Poelmann, RE
Poelmann, RE
中科院分区:
医学1区
文献类型:
--
作者:
Gittenberger-de Groot, AC;Peeters, MPFMV;Poelmann, RE

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已知心外膜和背侧系膜是形成冠状血管壁的结构的来源。由于小鼠基因敲除研究表明,适当的心外膜形成也是心肌发育所必需的,我们详细研究了心外膜衍生细胞(EPDCs)在发育心脏内的迁移和分化。我们构建了鸡鹌鹑嵌合体移植鹌鹑心外膜器官,包括一块原始肝脏,基本上在第16和17阶段。在第25至43阶段研究胚胎。为了检测鹌鹑来源的EPDCs,抗鹌鹑核抗体与几种分化标记物组合使用,例如,用于肌肉肌动蛋白、用于血管平滑肌细胞、用于前胶原-I、用于鹌鹑内皮和用于浦肯野纤维。在第25至31期,在心肌壁和内膜下区域遇到EPDC。后一种沉积在空间上是便利的,因为内膜通过心肌中的短暂不连续突出以接触心外膜下层。后来,在第32至43期,EPDCs通过房室沟侵入房室垫组织。定位在与心肌的界面处以及心内膜下是明显的,但从未在内膜内层内。根据已发表的数据,证实了心外膜移植物冠状血管壁的内皮细胞、平滑肌细胞和成纤维细胞的来源。新型EPDCs在内膜下、心肌和房室垫中的功能作用仍有待研究。一个密切的位置关系,发现与分化浦肯野纤维。此外,在心内膜间质转化的过程中的调节作用被假定。EPDCs的最终命运似乎是参与纤维心脏骨架形成的心脏成纤维细胞系。
The epicardium and dorsal mesocardium are known to be the source of structures that form the wall of the coronary vessels. Because mouse knockout studies have shown that proper epicardial formation is also essential for myocardial development, we have studied in detail the migration and differentiation of epicardium-derived cells (EPDCs) within the developing heart. We constructed chicken-quail chimeras by grafting the quail epicardial organ, including a piece of primordial Liver, at essentially stages 16 and 17. The embryos were studied at stages 25 to 43, To detect quail-derived EPDCs, an anti-quail nucleus antibody was used in combination with several differentiation markers, eg, for muscle actin, for vascular smooth muscle cells, for procollagen-I, for quail endothelium, and for Purkinje fibers. At stages 25 to 31, EPDCs are encountered in the myocardial wall and the subendocardial region. The latter deposition is spatially facilitated as the endocardium protrudes through transient discontinuities in the myocardium to contact the subepicardial layer. Later on, at stages 32 to 43, EPDCs invaded, by way of the atrioventricular sulcus, the atrioventricular cushion tissue. The localization is apparent at the interface with the myocardium, as well as subendocardially, but never within the endocardial lining. The origin of endothelium, smooth muscle cells, and fibroblasts of the coronary vessel wall from the epicardial graft were confirmed in accordance with already published data. The functional role of the novel EPDCs in the subendocardium, myocardium, and atrioventricular cushions remains to be investigated. A close positional relationship is found with the differentiating Purkinje fibers. Furthermore, a regulatory role is postulated in the process of endocardial-mesenchymal transformation. The ultimate fate of EPDCs seems to be a cardiac fibroblast cell line involved in the formation of the fibrous heart skeleton.