Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis.

ABSTRACT: The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory pro

SUBMITTER: Strunz M 

PROVIDER: S-EPMC7366678 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature