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Publication : Characterization of the platelet-derived growth factor receptor-?-positive cell lineage during murine late lung development.

First Author  Ntokou A Year  2015
Journal  Am J Physiol Lung Cell Mol Physiol Volume  309
Issue  9 Pages  L942-58
PubMed ID  26320158 Mgi Jnum  J:232876
Mgi Id  MGI:5780370 Doi  10.1152/ajplung.00272.2014
Citation  Ntokou A, et al. (2015) Characterization of the platelet-derived growth factor receptor-alpha-positive cell lineage during murine late lung development. Am J Physiol Lung Cell Mol Physiol 309(9):L942-58
abstractText  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-alpha-positive (PDGFRalpha(+)) cell populations during late lung development in mice. PDGFRalpha(+) cells (detected using a PDGFRalpha(GFP) reporter line) were noted around the proximal airways during the pseudoglandular stage. In the canalicular stage, PDGFRalpha(+) cells appeared in the more distal mesenchyme, and labeled alpha-smooth muscle actin-positive tip cells in the secondary crests and lipofibroblasts in the primary septa during alveolarization. Some PDGFRalpha(+) cells appeared in the mesenchyme of the adult lung. Over the course of late lung development, PDGFRalpha(+) cells consistently expressed collagen I, and transiently expressed markers of mesenchymal stem cells. With the use of both, a constitutive and a conditional PDGFRalpha(Cre) line, it was observed that PDGFRalpha(+) 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 PDGFRalpha(+) cell lineage to lipofibroblasts and myofibroblasts during late lung development that is needed to better understand the cellular contribution to the process of alveolarization.
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