有越来越多的证据表明城市污染对肺部健康有不良影响。然而，城市污染如何影响肺泡间质和上皮干细胞微环境目前尚不清楚。本研究旨在确定复杂的典型城市大气环境如何改变肺泡干细胞微环境特性。将小鼠放置在一种创新的装置中，该装置能够真实模拟巨大都市的大气环境，或者“洁净空气”环境，持续7天。收集肺组织并分离成纤维母细胞和上皮细胞（EpCAM+）。通过人口倍增水平（PDL）进行纤维母细胞增殖能力测试，并进行微阵列分析。将来自暴露、非暴露或原始状态小鼠的纤维母细胞和EpCAM+细胞进行器官样结构（organoid）培养，以评估干细胞特性。通过西鲁斯红染色法、脂肪纤维母细胞（ADRP）、肌纤维母细胞（COL1A1、αSMA）、肺泡2型细胞（AT2、SFTPC+）和肺泡分化中间细胞（ADI、KRT8+/CLDN4+）标记物在肺组织中进行定量分析。从暴露于城市大气环境的小鼠中获得的纤维母细胞其PDL和存活率较低，并且产生的器官样结构较少且较小。微阵列分析显示脂肪组织生成减少，并且与纤维化相关的基因增加，说明脂肪纤维母细胞向肌纤维母细胞转变。在城市大气环境暴露的小鼠肺组织中，胶原沉积和肌纤维母细胞数量增加。AT2细胞数量减少，并伴随KRT8+/CLDN4+的ADI细胞增加。此外，来自暴露小鼠的EpCAM+细胞也产生较少且较小的器官样结构。城市大气环境通过诱导脂肪纤维母细胞向肌纤维母细胞转变，改变了肺泡间质干细胞微环境特性。它还导致肺泡上皮功能异常和纤维化表型的出现。

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.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. Fibroblasts proliferative capacities were tested by population doubling levels (PDL) and microarray analyses were performed. Fibroblasts and EpCAM+ cells from exposed, non-exposed or naive mice were co-cultured in organoid assays to assess the stem cell properties. Collagen deposition (Sirius red), lipofibroblasts (ADRP), myofibroblasts (COL1A1, αSMA), alveolar type 2 cells (AT2, SFTPC+) and alveolar differentiation intermediate cell (ADI, KRT8+/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 lung of urban atmosphere exposed mice. AT2 number was reduced and associated with an increase of ADI cells KRT8+/CLDN4+. Furthermore, EpCAM+ cells from exposed mice also produced fewer and smaller organoids.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 phenotype.