Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype

We found histological evidence for increased abundance of iron accumulating cells in association with fibrotic lung, kidney, and heart diseases in mice and humans. We showed that inducing iron accumulation by intratracheal iron delivery in mice is a potent inducer of inflammation, cellular senescence, and fibrosis. The aim of this study has been to understand the single cell dynamics of iron accumulation and the mechanics that link it to in vivo senescence and to fibrogenesis. To get deeper insight into how different cell types respond to iron accumulation, we performed single nuclei RNA sequencing (snRNA-seq) of lungs from mice which received a single intratracheal dose of iron 2 or 6 days prior to analysis, or PBS 6days prior to analysis (control).