Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart.
Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart.
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DOI：
10.1016/j.ydbio.2009.12.007
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发表时间：
2010-02-15
影响因子：
2.7
通讯作者：
Pu, William T.
中科院分区：
文献类型：
--
作者：
Zhou, Bin;von Gise, Alexander;Ma, Qing;Hu, Yong Wu;Pu, William T.
纤维环使心房和心室电绝缘，使这些结构能够按时间顺序依次跳动，这对心脏有效功能是必需的。纤维环发育异常会导致心房到心室的附加电通路持续存在，为诸如预激综合征等折返性心律失常提供了解剖学基础。为了更好地理解纤维环的发育以及这些心律失常的病因，我们使用Cre - LoxP技术来评估心外膜衍生细胞（EPDCs）对纤维环的作用。我们发现EPDCs迁移到正在形成的纤维环区域，该区域以骨膜蛋白为标志。这些EPDCs对I型前胶原也呈阳性染色，表明EPDCs自身合成纤维环的蛋白质。为了进一步验证EPDCs对合成纤维环的细胞有贡献这一假设，我们从房室区域纯化了基因标记的EPDCs，并通过定量PCR测量基因表达。这些EPDCs高度富集编码骨膜蛋白、I型前胶原、I型纤连蛋白、波形蛋白、DDR2和腱糖蛋白C的mRNA，这些是成纤维细胞的标志物以及纤维环的组成成分。此外，这些EPDCs高度富集Snail、Smad1、Slug和Twist1（上皮 - 间质转化（EMT）的标志物）以及一种金属肽酶Mmp2（其有助于细胞迁移）。我们的工作首次提供了确凿的证据，表明心外膜通过EMT对哺乳动物纤维环的形成有贡献。这种分化过程的异常可能是某些形式的折返性房室心动过速发生的基础。
The annulus fibrosis electrically insulates the atria and ventricles, allowing the timed sequential beating of these structures that is necessary for efficient heart function. Abnormal development of the annulus fibrosis leads to persistence of accessory electrical pathways from atria to ventricles, providing the anatomical substrate for re-entrant cardiac arrhythmias such as Wolff-Parkinson-White syndrome. To better understand the development of the annulus fibrosis and the etiology of these cardiac arrhythmias, we used Cre-LoxP technology to assess the contribution of epicardium derived cells (EPDCs) to the annulus fibrosis. We found that EPDCs migrated into the region of the forming annulus fibrosis, marked by the protein periostin. These EPDCs also stained positive for procollagen I, suggesting that the EPDCs themselves synthesize proteins of the annulus fibrosis. To further test the hypothesis that EPDCs contribute to cells that synthesize the annulus fibrosis, we purified genetically marked EPDCs from the atrioventricular region and measured gene expression by quantitative PCR. These EPDCs were highly enriched for mRNAs encoding periostin, procollagen I, fibronectin I, vimentin, DDR2, and tenacin C, markers of fibroblasts and components of the annulus fibrosis. In addition, these EPDCs were highly enriched for Snail, Smad1, Slug, and Twist1, markers for epithelial to mesenchymal transition (EMT), and a metallopeptidase, Mmp2, that contributes to cellular migration. Our work provides for the first time definitive evidence that epicardium contributes to formation of the mammalian annulus fibrosis through EMT. Abnormalities of this differentiation process may underlie development of some forms of re-entrant atrioventricular tachycardia.
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影响因子：
2.7
作者：
Ma, Qing;Zhou, Bin;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
37.8
作者：
BECKER, AE;ANDERSON, RH;WELLENS, HJJ
通讯作者：
WELLENS, HJJ
影响因子：
7.7
作者：
Vooijs, M;Jonkers, J;Berns, A
通讯作者：
Berns, A
DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
Feil, R;Wagner, J;Chambon, P
通讯作者：
Chambon, P
影响因子：
64.8
作者：
Zhou, Bin;Ma, Qing;Pu, William T.
通讯作者：
Pu, William T.