Complex urban atmosphere alters alveolar stem cells niche properties and drives lung fibrosis.
Publication Year:
2023
PubMed ID:
37529852
Funding Grants:
Public Summary:
It is well known that urban pollution has adverse effects on lung health. However, how urban pollution affects different stem cell niches compartments remains unknown. This study aimed to establish a lung injury model that mimics complex urban atmospheres in order to determine how these atmospheres alter regeneration and stem cell activities in the lung. Lungs were collected, and two different alveolar cell types called fibroblasts and epithelial cells were isolated. We demonstrated that exposure to air pollution results in a fibrosis like phenotype in the lungs. Fibroblasts obtained from lungs exposed to urban atmosphere had lower proliferative capacity and lower survival. An organoid assay aimed to test the stemless of the cells was performed. Fibroblasts exposed to air pollution produced fewer and smaller organoids, suggesting a reduced stem cell support ability of these cells. Furthermore, epithelial cells from lungs exposed to pollution also produced fewer and smaller organoids. In conclusion, we demonstrated that urban atmosphere alters alveolar mesenchymal stem cell niche and epithelial stem cell properties.
Scientific Abstract:
There is growing evidence suggesting that urban pollution has adverse effects on lung health. However, how urban pollution affects alveolar mesenchymal and epithelial stem cell niches remains unknown. This study aimed to determine how complex representative urban atmospheres alter alveolar stem cell niche properties. Mice were placed in an innovative chamber realistically simulating the atmosphere of a megalopolis, or "clean air," for 7 days. Lungs were collected, and fibroblasts and epithelial cells (EpCAM(+)) were isolated. Proliferative capacities of fibroblasts were tested by population doubling levels (PDL), and microarray analyses were performed. Fibroblasts and EpCAM(+) cells from exposed, nonexposed, or naive mice were cocultured in organoid assays to assess the stem cell properties. Collagen deposition (Sirius red), lipofibroblasts (ADRP, COL1A1), myofibroblasts (alphaSMA), alveolar type 2 cells (AT2, SFTPC(+)), and alveolar differentiation intermediate cell [ADI, keratin-8-positive (KRT8(+))/claudin-4-positive (CLDN4(+))] markers were quantified in the lungs. Fibroblasts obtained from mice exposed to urban atmosphere had lower PDL and survival and produced fewer and smaller organoids. Microarray analysis showed a decrease of adipogenesis and an increase of genes associated with fibrosis, suggesting a lipofibroblast to myofibroblast transition. Collagen deposition and myofibroblast number increased in the lungs of urban atmosphere-exposed mice. AT2 number was reduced and associated with an increase in ADI cells KRT8(+)/CLDN4(+). Furthermore, EpCAM(+) cells from exposed mice also produced fewer and smaller organoids. In conclusion, urban atmosphere alters alveolar mesenchymal stem cell niche properties by inducing a lipofibroblast to myofibroblast shift. It also results in alveolar epithelial dysfunction and a fibrotic-like phenotype.NEW & NOTEWORTHY Urban pollution is known to have major adverse effects on lung health. To assess the effect of pollution on alveolar regeneration, we exposed adult mice to a simulated high-pollution urban atmosphere, using an innovative CESAM simulation chamber (Multiphase Atmospheric Experimental Simulation Chamber, https://cesam.cnrs.fr/). We demonstrated that urban atmosphere alters alveolar mesenchymal stem cell niche properties by inducing a lipofibroblast to myofibroblast shift and induces alveolar epithelial dysfunction.