Concurrent jamming and mesenchymal-to-epithelial transitions during airway basal stem cell differentiation

Under homeostatic conditions, the human airway epithelium remains well-differentiated, stable, and resistant to external insults. This collective transitions between a stationary and a migratory state under various circumstances, including cellular differentiation and pathological conditions such as asthma. As human airway basal stem cells differentiate and form a stable tissue, they transition from a collectively migratory, fluid-like, unjammed phase to a stationary, solid-like, jammed phase. Here, we demonstrate that jamming during basal stem cell differentiation coincides with the mesenchymal-to-epithelial transition (MET). We show that cells from patients with asthma exhibit delayed MET and jamming, both of which are accelerated by the inhibition of TGF-β receptor activity. Reciprocally, TGF-β priming of healthy cells delays both MET and jamming, mimicking the delayed transitions observed in asthmatic cells. Our data reveal a central role for both epithelial-mesenchymal and jamming transitions in the cellular plasticity and dynamics governing the differentiation of human airway basal stem cells.