Bronchioalveolar stem cells in lung repair, regeneration and disease.

Bronchioalveolar stem cells (BASCs) are a lung resident stem cell population located at bronchioalveolar duct junctions that contribute to the maintenance of bronchiolar club cells and alveolar epithelial cells of the distal lung. Their transformed counterparts are considered to be likely progenitors of lung adenocarcinomas, which has been a major area of research in relation to BASCs. A critical limitation in addressing the function of BASCs in vivo has been the lack of a unique BASC marker, which has prevented specific targeting of BASCs in animal models of respiratory conditions. Recently, there have been several studies describing genetically modified mice that allow in vivo quantification, tracing, and functional analysis of BASCs to address this long-standing issue. These cutting-edge experimental tools will likely have significant implications for future experimental studies involving BASCs and the elucidation of their role in various lung diseases. To date, this has been largely explored in models of lung injury including naphthalene-induced airway injury, bleomycin-induced alveolar injury, hyperoxia-induced models of bronchopulmonary dysplasia, and influenza virus infection. These novel experimental mouse tools will facilitate the assessment of the impact of BASC loss on additional respiratory conditions including infection-induced severe asthma and chronic obstructive pulmonary disease, as well as respiratory bacterial infections, both in early life and adulthood. These future studies may shed light on the potential broad applicability of targeting BASCs for a diverse range of respiratory conditions during lung development and in promoting effective regeneration and repair of the lung in respiratory diseases. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.