Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis
Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis
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DOI：
10.1091/mbc.e06-11-1052
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发表时间：
2007-05-01
影响因子：
3.3
通讯作者：
Mostov, Keith
中科院分区：
文献类型：
--
作者：
Yu, Wei;Fang, Xiaohui;Mostov, Keith
许多器官由被单层上皮细胞包围的中空腔组成。尽管它们具有共同的结构，但这些器官是通过不同的形态发生过程形成的。三维文化系统对于分析事件很有用。大多数过程需要细胞增殖和细胞死亡的结合来产生空腔。在这里，我们描述了一种新的三维培养系统，其中原代人肺泡 II 型细胞通过一种新的过程形成中空上皮囊肿。单个细胞移动、碰撞并形成肺泡样囊肿，但没有明显的增殖或凋亡。肺泡样囊肿由分化的 II 型肺泡细胞的极化单层组成，这些细胞将表面活性剂分泌到中央腔中。 β1整合素的阻断不会改变细胞运动或碰撞，但它大大减少了碰撞后细胞的粘附以及随后形成的肺泡样囊肿。用毛喉素治疗预先形成的肺泡样囊肿会增加其直径，这可能是由于刺激液体分泌到管腔中。我们得出的结论是，上皮分化和囊肿形成可以在没有明显增殖或凋亡的情况下发生。
Many organs consist of a hollow cavity surrounded by a monolayer of epithelial cells. Despite their common structure, such organs form by diverse morphogenetic processes. Three-dimensional culture systems have been useful in analyzing the events. Most processes require a combination of cell proliferation and cell death to produce a hollow cavity. Here, we describe a new three-dimensional culture system in which primary human lung alveolar type II cells formed hollow epithelial cysts by a novel process. Individual cells moved, collided, and formed alveolar-like cysts without appreciable proliferation or apoptosis. The alveolar-like cysts consisted of a polarized monolayer of differentiated alveolar type II cells, which secreted surfactant into the central lumen. Blockage of beta 1 integrin did not alter cell movement or collision, but it greatly reduced adhesion of cells after collision and subsequent formation of alveolar-like cysts. Treatment of preformed alveolar-like cysts with forskolin increased their diameter, possibly due to stimulation of fluid secretion into the lumen. We conclude that epithelial differentiation and cyst-formation can occur without appreciable proliferation or apoptosis.