PDGFRalpha and alphaSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Pulmonary fibrosis is characterized by pronounced collagen deposition and myofibroblast expansion, whose origin and plasticity remain elusive. We utilized a fate-mapping approach to investigate alpha-smooth muscle actin (alphaSMA)+ and platelet-derived growth factor receptor alpha (PDGFRalpha)+ cells in two lung fibrosis models, complemented by cell type-specific next-generation sequencing and investigations on human lungs. Our data revealed that alphaSMA+ and PDGFRalpha+ cells mark two distinct mesenchymal lineages with minimal transdifferentiation potential during lung fibrotic remodeling. Parenchymal and perivascular fibrotic regions were populated predominantly with PDGFRalpha+ cells expressing collagen, while alphaSMA+ cells in the parenchyma and vessel wall showed variable expression of collagen and the contractile protein desmin. The distinct gene expression profile found in normal conditions was retained during pathologic remodeling. Cumulatively, our findings identify alphaSMA+ and PDGFRalpha+ cells as two separate lineages with distinct gene expression profiles in adult lungs. This cellular heterogeneity suggests that anti-fibrotic therapy should target diverse cell populations.

• Biasin, V.
• Crnkovic, S.
• Sahu-Osen, A.
• Birnhuber, A.
• El Agha, E.
• Sinn, K.
• Klepetko, W.
• Olschewski, A.
• Bellusci, S.
• Marsh, L. M.
• Kwapiszewska, G.