Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart.

Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart.
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DOI:
10.1083/jcb.200504061
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发表时间:
2005-09-26
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Fukuda K
Fukuda K
中科院分区:
其他
文献类型:
--
作者:
Tomita Y;Matsumura K;Wakamatsu Y;Matsuzaki Y;Shibuya I;Kawaguchi H;Ieda M;Kanakubo S;Shimazaki T;Ogawa S;Osumi N;Okano H;Fukuda K

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啮齿动物心脏侧群体细胞片段在无血清培养基中形成克隆球体,表达nestin、Musashi-1和多药耐药转运基因1等未分化神经前体细胞标志物。这些标记物在分化后消失,取而代之的是神经元、胶质细胞、平滑肌细胞或心肌细胞特异性蛋白的表达。移植到鸡胚中的心球细胞迁移到动脉干和心流出道,并形成背根神经节、脊神经和主动脉平滑肌细胞。利用编码0-Cre /Floxed-EGFP蛋白的双转基因小鼠进行谱系研究,发现胎儿心肌中存在未分化和分化的神经嵴来源细胞。未分化的细胞表达gata结合蛋白4和巢蛋白,但不表达肌动蛋白,而分化的细胞被鉴定为心肌细胞。这些结果表明,心脏神经嵴来源的细胞迁移到心脏,作为休眠的多能干细胞留在那里,并在适当的条件下分化成心肌细胞和典型的神经嵴来源的细胞,包括神经元、胶质细胞和平滑肌。
Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell–, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0–Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells—and under the right conditions—differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle.
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