Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar-lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, damage-associated transient progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell…

• WT
  Wellcome Trust
• CR
  Cancer Research UK

  Award: T02233
• RS
  Royal Society

  Award: 107633/Z/15/Z
• MO
  Ministry of Education

  Award: 2017R1A6A3A03005399
• NR
  National Research Foundation of Korea
• NM
  NIHR Maudsley Biomedical Research Centre
• MR
  Medical Research Council

  Awards: MC_PC_12009, MC_PC_17230
• ER
  European Research Council

  Award: 679411