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Achaete‐scute homolque‐1 (ASH1) contributes to the expansion of airway stem cell population in peripheral lung
Author(s) -
JensenTaubman Sandra Mae,
Dakir El Habib,
DeMayo Francesco,
Linnoila Ilona
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb69-b
Subject(s) - stem cell , lung , biology , hyperplasia , epithelium , respiratory epithelium , microbiology and biotechnology , andrology , population , cell , respiratory system , immunology , anatomy , endocrinology , medicine , biochemistry , environmental health , genetics
Naphthalene exposure kills lung epithelial (Clara) cells, but is rapidly followed by Clara cell reconstitution coincident with proliferation of pulmonary neuroendocrine (NE) cells (PNEC), which involves both transient amplifying cells and stem cells. While ASH1 is critical for NE differentiation in lung, constitutive expression of human ASH1 in the airways leads to epithelial cell hyperplasia and bronchiolization of alveoli (BOA) in transgenic (TG) mice. The current study examines the impact of ASH1 on cellular repair following acute naphthalene toxicity. We show overall attenuation of PNEC hyperplasia in TG mice and retention of the Clara cell markers CC10 and CYP2F2 in BOA. It is notable that the label retention rate in BOA increased significantly and remained higher than that in the adjacent terminal airways of TG mice in response to naphthalene. In contrast, the induction of proliferation was more robust in terminal airway epithelium of wild type (15 fold increase) and TG (10 fold increase) mice than in BOA (5 fold increase). We conclude that the BOA of ASH1 TG mice features a subpopulation of cells that are chemo‐resistant and slowly replicating following naphthalene exposure, which are characteristics of stem cells. Our study merits further investigation into potential stem cell niches in murine distal lung. Source of Research Support: NCI