Evidence for Scgb1a1+ Cells in the Generation of p63+ Cells in the Damaged Lung Parenchyma

D Zheng, L Yin, J Chen - American journal of respiratory cell and …, 2014 - atsjournals.org
D Zheng, L Yin, J Chen
American journal of respiratory cell and molecular biology, 2014atsjournals.org
Transformation-related protein 63-expressing (p63+) basal cells are confined to the trachea
in the mouse lung. However, after influenza virus infection or bleomycin treatment, patches
of p63+ cells were observed in the damaged lung parenchyma. To address whether the
newly induced p63+ cells are derived from the p63+ basal cells, we performed lineage
tracing. In a keratin 5 promoter–driven CreER system, although preexisting p63+ basal cells
were labeled by enhanced green fluorescent protein (EGFP) after tamoxifen treatment, none …
Transformation-related protein 63-expressing (p63+) basal cells are confined to the trachea in the mouse lung. However, after influenza virus infection or bleomycin treatment, patches of p63+ cells were observed in the damaged lung parenchyma. To address whether the newly induced p63+ cells are derived from the p63+ basal cells, we performed lineage tracing. In a keratin 5 promoter–driven CreER system, although preexisting p63+ basal cells were labeled by enhanced green fluorescent protein (EGFP) after tamoxifen treatment, none or only a small fraction (∼ 15%) of the p63+ patches was labeled by EGFP after bleomycin treatment or influenza virus infection, respectively. In contrast, > 60% of p63+ patches contained EGFP+ cells in Scgb1a1-CreER transgenic system where club cells are labeled. Many p63+ cells were found in bronchiole-like lumen structures with columnar cells at the lumen side. The columnar cells were positive for club cell marker Cyp2f2 and could be traced to the newly induced p63+ cells. These results suggest that most of the newly induced p63+ cells in the damaged parenchyma are likely derived from club cells rather than from p63+ basal cells and that newly induced p63+ cells may be involved in the regeneration of bronchioles.
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