Ciliated cells differentiated from mouse embryonic stem cells
Ciliated cells differentiated from mouse embryonic stem cells
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DOI：
10.1634/stemcells.2005-0464
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发表时间：
2006-05-01
期刊：
影响因子：
5.2
通讯作者：
Asashima, Makoto
中科院分区：
文献类型：
--
作者：
Nishimura, Yusuke;Hamazaki, Tatsuo S.;Asashima, Makoto
在本研究中，我们证明了小鼠胚胎干细胞分化为纤毛上皮细胞，具有正常纤毛细胞的特征。这些细胞表达纤毛标记蛋白，如β -微管蛋白IV和肝细胞核因子-3/叉头同源物4 (hhh -4)，加工后的微管呈9 + 2结构排列，这与正常纤毛微管的特异性排列相同。这些细胞的纤毛以17-20赫兹的频率跳动。含有这些纤毛细胞的分化胚状体（EBs）表达甲状腺转录因子-1和表面活性剂蛋白- c等呼吸标志基因。为了诱导纤毛细胞，在附着的最初2天内，在无血清培养基中培养EBs是必不可少的。骨形态发生蛋白处理后，hhh -4表达降低，纤毛细胞分化不明显。以前从胚胎或成人组织中体外诱导纤毛细胞的方法涉及气液界面。本研究中使用的系统更接近于模拟纤毛细胞的正常发育；因此，该系统的另一个优点是可以作为研究正常纤毛上皮细胞分化机制的工具。
In the present study, we demonstrated that the mouse embryonic stem cells were differentiated into ciliated epithelial cells, with characteristics of normal ciliated cells. These cells expressed ciliary marker proteins, such as beta-tubulin IV and hepatocyte nuclear factor-3/forkhead homolog 4 (HFH-4), and processed microtubules were arranged in the 9 + 2 structure, which is the same specific alignment observed in normal ciliary microtubules. The cilia of these cells were beating at a frequency of 17-20 Hz. The differentiated embryoid bodies (EBs) containing these ciliated cells expressed respiratory marker genes such as thyroid transcription factor-1 and surfactant protein-C. For the induction of ciliated cells, culture of EBs in serum-free medium during the initial 2 days of the attachment was indispensable. When EBs were treated with bone morphogenetic proteins, the expression of HFH-4 was decreased, and the ciliated cells were scarcely differentiated. Previous methods for inducing ciliated cells in vitro from embryonic or adult tissues involved an air-liquid interface. The system used in this study more closely mimics the normal development of ciliated cells; thus, an added advantage of the system is as a tool for studying the differentiation mechanism of normal ciliated epithelial cells.