Airway Hillocks are Injury-Resistant Reservoirs of Plastic Stem Cells

Airway hillocks are newly described discrete epithelial structures of unknown function that are distinct from the classic pseudostratified epithelium lining the airway lumen. We show that hillocks are islands of stratified epithelia harboring migratory stem cells that are capable of extensive clonal expansion. Hillocks resist a broad range of injuries, preserving a basal stem cell population that ultimately resurfaces the airway lining. The fully resurfaced hillock epithelium then exhibits plasticity and converts into a normal pseudostratified epithelium indistinguishable from its healthy, uninjured counterpart. Overall design: We performed plate-based SMART-Seq2 on hillock vs pseudostratified epithelium that was microdissected from a p63-CreER;LSL-TdTomato mouse