Endocardial cells are a distinct endothelial lineage derived from Flk1+multipotent cardiovascular progenitors
Endocardial cells are a distinct endothelial lineage derived from Flk1+multipotent cardiovascular progenitors
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DOI：
10.1016/j.ydbio.2009.06.033
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发表时间：
2009-09-01
影响因子：
2.7
通讯作者：
Baldwin, H. Scott
中科院分区：
文献类型：
--
作者：
Misfeldt, Andrew M.;Boyle, Scott C.;Baldwin, H. Scott
多能心脏祖细胞的鉴定为心肌谱系指定的机制提供了重要的见解，但对阐明心内膜的起源几乎没有什么作用。尽管心内膜在心脏发育中起着重要作用，但由于缺乏这一早期血管亚群的特异性标志物，心内膜谱系的特征一直受到限制。为了区分心内膜和其他血管，我们建立了NFATc1-nuc-lacZ BAC转基因小鼠系，能够在心脏发育的最早阶段标记这种特定的内皮亚群。为了进一步研究心内膜的发生，来自NFATc1-nuc-LacZ胚泡的胚胎干细胞(ESCs)被用来证明体外培养的心内膜分化重现了体内观察到的心肌和心内膜之间密切的时空关系。心内膜被指定为一种独立于其他血管细胞的心肌细胞系，对促进心肌细胞分化的BMP和Wnt信号做出反应。此外，Flk1+心血管前体细胞不同于血管母细胞前体细胞，代表着心内膜内皮细胞和其他心血管血统的中胚层前体细胞。综上所述，这些研究强调心内膜是一种独特的心脏谱系，并提供了进一步的证据，证明心内膜和心肌起源于共同的前体。(C)2009年，爱思唯尔公司出版。
Identification of multipotent cardiac progenitors has provided important insights into the mechanisms of myocardial lineage specification, yet has done little to clarify the origin of the endocardium. Despite its essential role in heart development, characterization of the endocardial lineage has been limited by the lack of specific markers of this early vascular subpopulation. To distinguish endocardium from other vasculature, we generated an NFATc1-nuc-LacZ BAC transgenic mouse line capable of labeling this specific endothelial subpopulation at the earliest stages of cardiac development. To further characterize endocardiogenesis, embryonic stem cells (ESCs) derived from NFATc1-nuc-LacZ blastocysts were utilized to demonstrate that endocardial differentiation in vitro recapitulates the close temporal-spatial relationship observed between myocardium and endocardium seen in vivo. Endocardium is specified as a cardiac cell lineage, independent from other vascular populations, responding to BMP and Wnt signals that enhance cardiomyocyte differentiation. Furthermore, a population of Flk1+ cardiovascular progenitors, distinct from hemangioblast precursors, represents a mesodermal precursor of the endocardial endothelium, as well as other cardiovascular lineages. Taken together, these studies emphasize that the endocardium is a unique cardiac lineage and provides further evidence that endocardium and myocardium are derived from a common precursor. (C) 2009 Published by Elsevier Inc.