In vitro transdifferentiation of human fetal type II cells toward a type I-like cell
In vitro transdifferentiation of human fetal type II cells toward a type I-like cell
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DOI：
10.1203/pdr.0b013e3180332c6d
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发表时间：
2007-04-01
影响因子：
3.6
通讯作者：
Guttentag, Susan H.
中科院分区：
文献类型：
--
作者：
Foster, Cherie D.;Varghese, Linda S.;Guttentag, Susan H.
对于肺泡Ⅰ型细胞，由于在原代培养中分离和维持Ⅰ型细胞存在体外研究困难，除气体交换外的表型可塑性和生理学特性有待进一步阐明。利用一种已建立的人胎儿Ⅱ型细胞体外模型（在该模型中，通过添加激素诱导并维持Ⅱ型表型），我们评估了在培养过程中，在去除激素长达144小时后向Ⅰ型样细胞的转分化情况，随后进行了电子显微镜检查、通透性研究以及RNA和蛋白质分析。激素撤除导致Ⅱ型细胞特征减弱，包括微绒毛、板层小体以及Ⅱ型细胞标志物RNA和蛋白质减少。同时Ⅰ型细胞特征增加，包括上皮细胞屏障功能增强（表明形成紧密的单层）以及Ⅰ型细胞标志物RNA和蛋白质增加。我们的研究结果表明，从培养的人胎儿Ⅱ型细胞中去除激素会导致向Ⅰ型样细胞转分化。该模型将有助于对人胎儿肺泡上皮细胞分化和表型可塑性进行持续的体外研究。
For alveolar type I cells, phenotype plasticity and physiology other than gas exchange await further clarification due to in vitro study difficulties in isolating and maintaining type I cells in primary culture. Using an established in vitro model of human fetal type II cells, in which the type II phenotype is induced and maintained by adding hormones, we assessed for transdifferentiation in culture toward a type I-like cell with hormone removal for up to 144 h, followed by electron microscopy, permeability studies, and RNA and protein analysis. Hormone withdrawal resulted in diminished type II cell characteristics, including decreased microvilli, lamellar bodies, and type II cell marker RNA and protein. There was a simultaneous increase in type I characteristics, including increased epithelial cell barrier function indicative of a tight monolayer and increased type I cell marker RNA and protein. Our results indicate that hormone removal from cultured human fetal type II cells results in transdifferentiation toward a type I-like cell. This model will be useful for continued in vitro studies of human fetal alveolar epithelial cell differentiation and phenotype plasticity.