Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.

ABSTRACT: After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5^pos basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5^pos basal-like state. Activated murine Krt5^pos LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and sq

SUBMITTER: Xi Y 

PROVIDER: S-EPMC5600325 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature