Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro

Thai Yen Ling, Ming Der Kuo, Chung Leung Li, Alice L. Yu, Yen Hua Huang, Tsai Jung Wu, You Chin Lin, Shu Hwa Chen, John Yu

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

In this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamer-binding 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.

Original languageEnglish
Pages (from-to)9530-9535
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number25
DOIs
Publication statusPublished - Jun 20 2006

Keywords

  • Differentiation
  • Expression of Oct-4
  • Lung stem/progenitor cells
  • Slow-cycling cells

ASJC Scopus subject areas

  • Genetics
  • General

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