PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis.
Valentina BiasinSlaven CrnkovicAnita Sahu-OsenAnna BirnhuberElie El AghaKatharina SinnWalter KlepetkoAndrea OlschewskiSaverio BellusciLeigh Matthew MarshGrazyna KwapiszewskaPublished in: American journal of physiology. Lung cellular and molecular physiology (2020)
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 α-smooth muscle actin (αSMA)+ and platelet-derived growth factor receptor α (PDGFRα)+ cells in two lung fibrosis models, complemented by cell type-specific next-generation sequencing and investigations on human lungs. Our data revealed that αSMA+ and PDGFRα+ cells mark two distinct mesenchymal lineages with minimal transdifferentiation potential during lung fibrotic remodeling. Parenchymal and perivascular fibrotic regions were populated predominantly with PDGFRα+ cells expressing collagen, while αSMA+ 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 αSMA+ and PDGFRα+ 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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- pulmonary fibrosis
- growth factor
- single cell
- smooth muscle
- stem cells
- endothelial cells
- poor prognosis
- bone marrow
- cell death
- idiopathic pulmonary fibrosis
- endoplasmic reticulum stress
- skeletal muscle
- copy number
- long non coding rna
- squamous cell carcinoma
- mesenchymal stem cells
- genome wide
- transcription factor
- neoadjuvant chemotherapy
- big data
- gene expression
- young adults
- climate change
- epithelial mesenchymal transition
- cell therapy
- human health
- induced pluripotent stem cells