Catecholamine-synthesizing cells in the embryonic mouse heart.

Catecholamine-synthesizing cells in the embryonic mouse heart.
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DOI:
10.1196/annals.1410.008
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发表时间:
2008-12
影响因子:
5.2
通讯作者:
Pfeifer K
Pfeifer K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ebert SN;Rong Q;Boe S;Pfeifer K

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在胚胎发育过程中,心脏是肾上腺素和去甲肾上腺素的主要来源,但对产生这些儿茶酚胺激素的心脏细胞知之甚少。为了确定儿茶酚胺合成细胞在胚胎心脏中的时间和位置,我们通过将cree -重组酶基因“敲入”肾上腺素生物合成酶苯乙醇胺n-甲基转移酶(pnmt)的基因座,建立了一种新的小鼠遗传模型。当与ROSA26报告基因(R26R)小鼠杂交时,β-半乳糖苷酶基因在肾上腺素能细胞中被激活。这种方法的一个主要优点是,它允许检测肾上腺素能细胞及其后代,而不管后代细胞是否保留肾上腺素能表型。我们的数据显示,肾上腺素能细胞早在胚胎第8.5天(E8.5)就出现了,并在小鼠心脏出生时继续大量积累,在那里它们似乎与心肌谱系具有共同的祖先。大量的心房肌细胞,尤其是心室肌细胞似乎来源于心脏的胚胎肾上腺素能细胞。此外,窦房结和房室结中的许多起搏细胞似乎也来自肾上腺素能谱系。因此,我们的研究结果表明,儿茶酚胺合成细胞在胚胎心脏中充当心肌细胞祖细胞。
The heart is a primary source of epinephrine and norepinephrine during embryonic development, yet little is known about the cardiac cells that produce these catecholamine hormones. To identify when and where catecholamine-synthesizing cells are found in the embryonic heart, we developed a novel mouse genetic model by “knocking-in” the cre-recombinase gene to the locus encoding for the epinephrine biosynthetic enzyme, phenylethanolamine n-methyltransferase (pnmt). When crossed with ROSA26 reporter (R26R) mice, the β-galactosidase gene is activated in adrenergic cells. A major advantage of this approach is that it allows detection of adrenergic cells and their progeny, regardless of whether the progeny cells retain an adrenergic phenotype or not. Our data show that adrenergic cells appear as early as embryonic day 8.5 (E8.5) and continue to accumulate in substantial numbers through birth in the mouse heart where they appear to share common ancestry with myocardial lineages. Large numbers of atrial and especially ventricular myocytes appear to be derived from embryonic adrenergic cells in the heart. In addition, many of the pacemaking cells in the sinoatrial and atrioventricular nodes also appear to be derived from an adrenergic lineage. Thus, our results suggest that catecholamine synthesizing cells serve as cardiomyocyte progenitors in the embryonic heart.
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