Identification of Pulmonary Oct-4⁺ Stem/progenitor Cells and Demonstration of Their Susceptibility to SARS Coronavirus (SARS-CoV) Infection in vitro

In this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamerbinding transcription factor 4⁺ (Oct-4⁺) epithelial colonies with a surrounding mesenchymal stroma. In addition to Oct-4, these cells also express other stem cell markers s...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2006-06, Vol.103 (25), p.9530-9535
Hauptverfasser: Ling, Thai-Yen, Kuo, Ming-Der, Li, Chung-Leung, Yu, Alice L., Huang, Yen-Hua, Wu, Tsai-Jung, Lin, You-Chin, Chen, Shu-Hwa, Yu, John
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container_end_page 9535
container_issue 25
container_start_page 9530
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 103
creator Ling, Thai-Yen
Kuo, Ming-Der
Li, Chung-Leung
Yu, Alice L.
Huang, Yen-Hua
Wu, Tsai-Jung
Lin, You-Chin
Chen, Shu-Hwa
Yu, John
description In this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamerbinding transcription factor 4⁺ (Oct-4⁺) epithelial colonies with a surrounding mesenchymal stroma. In addition to Oct-4, these cells also express other stem cell markers such as stage-specific embryonic antigen 1 (SSEA-1), stem cell antigen 1 (Sca-1), and Clara cell secretion protein (CCSP) but not c-Kit, CD34, and p63, indicating that they represent a subpopulation of Clara cells that have been implicated as lung stem/progenitor cells in lung injury models. These colony cells can be kept for weeks in primary cultures and undergo terminal differentiation to alveolar type-2- and type-1-like pneumocytes sequentially when removed from the stroma. In addition, we have demonstrated the presence of Oct-4⁺ long-term BrdU label-retaining cells at the bronchoalveolar junction of neonatal lung, providing a link between the Oct-4⁺ cells in vivo and in vitro and strengthening their identity as putative neonatal lung stem/progenitor cells. Lastly, these Oct-4⁺ epithelial colony cells, which also express angiotensin-converting enzyme 2, are the target cells for severe acute respiratory syndrome coronavirus infection in primary cultures and support active virus replication leading to their own destruction. These observations imply the possible involvement of lung stem/progenitor cells, in addition to pneumocytes, in severe acute respiratory syndrome coronavirus infection, accounting for the continued deterioration of lung tissues and apparent loss of capacity for lung repair.
doi_str_mv 10.1073/pnas.0510232103
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subjects Animals
Biological Sciences
Biomarkers
Bromodeoxyuridine
Cell culture techniques
Cell Differentiation
Cell lines
Cells, Cultured
Cellular immunity
Cultured cells
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - metabolism
Epithelial Cells - virology
Gene Expression Regulation
Infections
Lung - cytology
Lung - virology
Lungs
Mesenchymal stem cells
Mice
Mice, Inbred ICR
Microscopy, Electron, Transmission
Octamer Transcription Factor-3 - metabolism
SARS virus
Severe acute respiratory syndrome-related coronavirus - physiology
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stem Cells - virology
title Identification of Pulmonary Oct-4⁺ Stem/progenitor Cells and Demonstration of Their Susceptibility to SARS Coronavirus (SARS-CoV) Infection in vitro
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