title: Characterization of the platelet-derived growth factor receptor-α-positive cell lineage during murine late lung development.
abstract: A reduced number of alveoli is the structural hallmark of diseases of the neonatal and adult lung, where alveoli either fail to develop (as in bronchopulmonary dysplasia), or are progressively destroyed (as in chronic obstructive pulmonary disease). To correct the loss of alveolar septa through therapeutic regeneration, the mechanisms of septa formation must first be understood. The present study characterized platelet-derived growth factor receptor-α-positive (PDGFRα(+)) cell populations during late lung development in mice. PDGFRα(+) cells (detected using a PDGFRα(GFP) reporter line) were noted around the proximal airways during the pseudoglandular stage. In the canalicular stage, PDGFRα(+) cells appeared in the more distal mesenchyme, and labeled α-smooth muscle actin-positive tip cells in the secondary crests and lipofibroblasts in the primary septa during alveolarization. Some PDGFRα(+) cells appeared in the mesenchyme of the adult lung. Over the course of late lung development, PDGFRα(+) cells consistently expressed collagen I, and transiently expressed markers of mesenchymal stem cells. With the use of both, a constitutive and a conditional PDGFRα(Cre) line, it was observed that PDGFRα(+) cells generated alveolar myofibroblasts including tip cells of the secondary crests, and lipofibroblasts. These lineages were committed before secondary septation. The present study provides new insights into the time-dependent commitment of the PDGFRα(+) cell lineage to lipofibroblasts and myofibroblasts during late lung development that is needed to better understand the cellular contribution to the process of alveolarization.
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany;
authors: Aglaia
authors: A
authors: Ntokou
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany;
authors: Friederike
authors: F
authors: Klein
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany;
authors: Daria
authors: D
authors: Dontireddy
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany;
authors: Sven
authors: S
authors: Becker
authors: Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany;
authors: Saverio
authors: S
authors: Bellusci
authors: Wolfson Institute for Biomedical Research, University College London, London, United Kingdom; and.
authors: William D
authors: WD
authors: Richardson
authors: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.
authors: Marten
authors: M
authors: Szibor
authors: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.
authors: Thomas
authors: T
authors: Braun
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany; Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany;
authors: Rory E
authors: RE
authors: Morty
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany; Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany;
authors: Werner
authors: W
authors: Seeger
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany;
authors: Robert
authors: R
authors: Voswinckel
authors: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL)], Bad Nauheim, Germany; Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany; katrin.ahlbrecht@mpi-bn.mpg.de.
authors: Katrin
authors: K
authors: Ahlbrecht
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000196:embryology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D024042:Collagen Type I; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: fibroblast precursor; lipofibroblast; myofibroblast; septation