TY - JOUR
T1 - Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis
AU - Yu, Wei
AU - Fang, Xiaohui
AU - Ewald, Andrew
AU - Wong, Kit
AU - Hunt, C. Anthony
AU - Werb, Zena
AU - Matthay, Michael A.
AU - Mostov, Keith
PY - 2007/5
Y1 - 2007/5
N2 - 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 β1 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.
AB - 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 β1 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.
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U2 - 10.1091/mbc.E06-11-1052
DO - 10.1091/mbc.E06-11-1052
M3 - Article
C2 - 17332496
AN - SCOPUS:34248223108
VL - 18
SP - 1693
EP - 1700
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 5
ER -