Abstract
Pulmonary diseases of the lung are characterized by a loss (chronic obstructive lung disease) or impaired formation (bronchopulmonary dysplasia) of the alveolar structure. New therapeutic concepts are urgently needed since therapeutic options are not available. Fibroblasts subtypes such as the lipofibroblasts (LFs), myofibroblasts (MFs) and PDGFRα+ fibroblasts, have been demonstrated to be key players in the lung during alveolarization but their distinct functions remain unknown. The present study aimed to characterize and elucidate the role of LFs during alveolarization using CreloxP based approaches for linage tracing. The localization, mode of differentiation and function of the LFs subset during alveolarization was analyzed. Double transgenic mice which stably express a red (Tomato) fluorophore lose the red label and acquire a green fluorescent protein (GFP) fluorophore label upon Cre recombinase activation. Using a novel ADRPCreERT2 mouse line crossed with a stop/loxP reporter-line, we investigated the dynamics in the lipofibroblast population throughout development. Postnatal transgenic mice treated with tamoxifen at postnatal days P1, P7, and P10 permitted the temporal delineation of the appearance, and spatial delineation of the localization of lipofibroblasts at postnatal day (P)14. These data revealed spatiotemporal changes in LFs in the developing lung, where LFs were present in the lung on P0, and decreased over time in the distal (developing) lung. By P14, the bulk of the remaining LFs were also PDGFRα+, but SMA-. These data add to a growing body of evidence that fibroblast phenotypes are plastic and that transdifferentiation phenotypes between PDGFRα+ fibroblasts, LFs, and SMA+ fibroblasts may overlap.
- Copyright ©the authors 2016