Fig. 10: A revised model of alveolar regeneration. | Nature Communications

Fig. 10: A revised model of alveolar regeneration.

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

Fig. 10

We identify convergence of alveolar and airway stem cells on an injury-induced transitional cell state characterized by a unique transcriptional signature, including high levels of Krt8 expression, that precedes the regeneration of AT1 cells. In this process, stem cells lose cell identity genes, gain specific gene programs including p53 and NFkB target genes, and undergo a drastic change in shape towards a squamous morphology. Krt8+ ADI cells feature a highly distinct connectome of receptor-ligand pairs with endothelial cells, fibroblasts, and macrophages. The Krt8+ ADI cell state persists in models of progressive lung fibrosis and human IPF patients, suggesting that the cell state transitions described in this work are coordinated in space and time by cell intrinsic and tissue niche checkpoints that may be derailed in disease.

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