title: Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis.
abstract: The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial-mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.
authors.affiliation: 1 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.|2 Department of Pediatric Cardiology and Critical Care, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: von Gise
authors.affiliation: 1 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Stevens
authors.affiliation: 1 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Leah B
authors.initials: LB
authors.lastname: Honor
authors.affiliation: 1 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Oh
authors.affiliation: 1 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Chi
authors.initials: C
authors.lastname: Gao
authors.affiliation: 3 Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: 1 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.|4 Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts.
authors.forename: William T
authors.identifier: http://orcid.org/0000-0002-4551-8079
authors.initials: WT
authors.lastname: Pu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D019070:Cell Lineage; D049109:Cell Proliferation; D058948:Cell Tracking; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D001761:Bleomycin
keywords: epithelial–mesenchymal transition; idiopathic pulmonary fibrosis; pulmonary mesothelium