Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Division of Pediatric Cardiology, New Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Nat Commun. 2021 Mar 10;12(1):1565. doi: 10.1038/s41467-021-21865-2.
During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia with validation of some of the findings in lungs from BPD patients. We observe dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, stromal fibroblasts, capillary endothelium and macrophage populations. Pathway analysis and predicted dynamic cellular crosstalk suggest inflammatory signaling as the main driver of hyperoxia-induced changes. Our data provides a single-cell view of cellular changes associated with late lung development in health and disease.
在肺的晚期发育过程中，肺泡和微血管的发育最终完成，以实现足够的气体交换。晚期肺发育受损表现为早产儿的支气管肺发育不良（BPD）。单细胞 RNA 测序（scRNA-seq）可评估发育等生物学过程中的复杂细胞动态。在这里，我们使用 MULTI-seq 生成了 36 只小鼠在正常或高氧诱导的肺发育受损期间超过 66,000 个细胞的 scRNA-seq 图谱，并在 BPD 患者的肺组织中验证了其中一些发现。我们观察到细胞的动态群体，包括几种稀有细胞类型和潜在的祖细胞。高氧暴露模拟了 BPD 表型，改变了所有细胞区室的组成，特别是肺泡上皮、基质成纤维细胞、毛细血管内皮和巨噬细胞群体。通路分析和预测的动态细胞串扰表明炎症信号是高氧诱导变化的主要驱动因素。我们的数据提供了一种单细胞视角，可了解健康和疾病中晚期肺发育相关的细胞变化。
