Pdgfra marks a cellular lineage with distinct contributions to myofibroblasts in lung maturation and injury response.
Pdgfra-expressing (Pdgfra+) cells have been implicated as progenitors in many mesenchymal tissues. To determine lineage potential, we generated Pdgfra knockin mice using CRISPR/Cas9. During lung maturation, counter to a prior study reporting that Pdgfra+ cells give rise equally to myofibroblasts and lipofibroblasts, lineage tracing using Pdgfra mice indicated that ~95% of the lineaged cells are myofibroblasts. Genetic ablation of Pdgfra cells using Pdgfra-driven diphtheria toxin (DTA) led to alveolar simplification, demonstrating that these cells are essential for building the gas exchange surface area. In the adult bleomycin model of lung fibrosis, lineaged cells increased to contribute to pathological myofibroblasts. In contrast, in a neonatal hyperoxia model of bronchopulmonary dysplasia (BPD), lineaged cells decreased and do not substantially contribute to pathological myofibroblasts. Our findings revealed complexity in the behavior of the Pdgfra-lineaged cells as exemplified by their distinct contributions to myofibroblasts in normal maturation, BPD and adult fibrosis.
['Li|Rongbo|R|0000-0001-9112-9712', 'Bernau|Ksenija|K|', 'Sandbo|Nathan|N|', 'Gu|Jing|J|', 'Preissl|Sebastian|S|', 'Sun|Xin|X|0000-0001-8387-4966']
D000818:Animals D001761:Bleomycin D064113:CRISPR-Cas Systems D019070:Cell Lineage D049109:Cell Proliferation D004195:Disease Models, Animal D017353:Gene Deletion D020869:Gene Expression Profiling D055879:Gene Knock-In Techniques D049452:Green Fluorescent Proteins D059765:Homologous Recombination D018496:Hyperoxia D008168:Lung D008822:Mice, Transgenic D058628:Myofibroblasts D011658:Pulmonary Fibrosis D020796:Receptor, Platelet-Derived Growth Factor alpha D059010:Single-Cell Analysis
myofibroblasts lung development developmental biology mouse regenerative medicine stem cells