Alveolar and airway progenitors converge on an epigenetically encoded profibrotic state

In mouse pulmonary fibrosis, a profibrotic KRT5-/KRT17+ transitional state arises convergently from alveolar type 2 and airway secretory cells, not from AT1 cells.

• Why it matters: The study addresses which epithelial progenitors generate fibrotic transitional states and how these states become epigenetically stabilized and persist during fibrosis.
• What they did: Using lineage tracing in mice, it maps KRT5-/KRT17+ origins to AT2 and airway secretory cells, and shows TGF-{beta}/SMAD3 reprograms human AT2 cells via KMT2A and p300.
• The result: In human pulmonary fibrosis, KRT5-/KRT17+ cells slough off while transitional cells re-epithelialize denuded basement membrane, supporting accumulation of a conserved profibrotic state through turnover and nominating the transition and epigenetic regulators as targets.

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