Acute Lung Injury Associated Milieus Regulate the Plasticity of Type I Alveolar Cells via KLF2

Efficient repair and regeneration of alveolar epithelium after acute lung injuries are critical for pulmonary maintenance. Previous studies suggested alveolar type II cells (ATIIs) are progenitors in the adult lung and Alveolar Type I cells (ATIs) are terminally differentiated. However, recent studies develop fresh perspectives, which suggest ATIs may play more roles. Here we show that ATIs exhibit markedly enhanced proliferation capacity and express a set of ATIIs associated genes after treated with damaged lung milieus. These changed characteristics suggest ATIs generate phenotypic plasticity and exhibit dedifferentiated state. We identify KLF2 as a regulator of the module. Knockdown of KLF2 induces gene expression is consistent to those observed in milieu treated cells. These findings demonstrate the unanticipated plasticity of ATIs and suggest the molecular mechanisms controlling ATI-ATII plasticity which deserve more explorations.