Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis.

ABSTRACT: Stem cells undergo dynamic changes in response to injury to regenerate lost cells. However, the identity of transitional states and the mechanisms that drive their trajectories remain understudied. Using lung organoids, multiple in vivo repair models, single-cell transcriptomics and lineage tracing, we find that alveolar type-2 epithelial cells undergoing differentiation into type-1 cells acquire pre-alveolar type-1 transitional cell state (PATS) en route to terminal maturation. Transitional cells undergo extensive stretching during differentiation, making them vulnerable to DNA damage. Cells in the PATS show an enrichment of TP53, TGFβ, DNA-damage-response signalling and cellular senescence. Gain and loss of function as well as genomic binding assays revealed a direct transcriptional cont

SUBMITTER: Kobayashi Y 

PROVIDER: S-EPMC7461628 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature