Lingampally and colleagues from the Institute for Lung Health identified a subcluster of activated myofibroblasts (aMYFs) that may have significant implications the future management of idiopathic pulmonary fibrosis (IPF).

IPF is a progressive, irreversible lung disease characterized by excessive extracellular matrix deposition. From a cell biology perspective, aMYFs are thought to secrete extracellular matrix and drive structural remodeling.

Using genetic lineage tracing and single-cell transcriptomics, Lingampally and colleagues investigated the origin of aMYFs and their differentiation trajectories during the process of fibrosis formation and resolution.

For the first time, the researchers demonstrate the heterogeneity of aMYFs, identifying subclusters with differing roles - some exhibit distinct pro-alveologenic, while others pro-fibrotic properties. Lipofibroblasts play a major role in emergence and fate of aMYFs during fibrogenesis and resolution, respectively.

This work provides new insights into the cellular dynamics of IPF and may inform future therapeutic strategies to treat or reverse fibrosis.

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Evidence for a lipofibroblast-to- Cthrc1 + myofibroblast reversible switch during the development and resolution of lung fibrosis in young mice - PubMed