Developmental Ontogeny of Bronchio‐Alveolar Stem Cells

Recent studies have revealed the existence of Bronchio‐Alveolar Stem Cells (BASCs), a population of airway‐derived progenitor cells identified by co‐expression of Clara cell secretory protein (CCSP) and surfactant protein C (SPC), which are capable of airway and airspace maintenance/repair. In an effort to determine the role of BASCs in lung development, we have investigated the developmental ontogeny of these cells. We assessed the frequency and distribution of BASC in the mouse lung by co‐immunofluorescence staining for CCSP and SPC. No change in the spatial distribution of BASC was observed. However, a significant change (p=0.03) in the frequency of these cells was seen from birth through 8 weeks of age. At 8 weeks of age, we observed a mean of 0.55 BASC/Bronchio‐Alveolar Duct Junction (BADJ), in good agreement with previous studies. The abundance of BASC steadily increased throughout postnatal maturation; 0.20 BASC/BADJ at 1 week, 0.42 BASC/BADJ at 2 weeks, 0.46 BASC/BADJ at 4 weeks and 0.55 BASC/BADJ at 8 weeks of age. This was due to a parallel decrease in the frequency of BADJ containing no BASC (81%, 80%, 65% and 57% at 1, 2, 4 and 8 weeks of age, respectively) and an increase in the frequency of BADJ containing two or more BASC (2%, 4%, 9% and 12% at 1, 2, 4 and 8 weeks of age, respectively). Few, if any, BASC were observed in the lungs of newborn mice. These data indicate that BASC may not be critical at the time of birth, but may be necessary for normal lung maintenance and repair. Funded by NHLBI, NIEHS and FAMRI