Single cell RNA analysis identifies cellular heterogeneity and adaptive responses of the lung at birth

TLDR

The respiratory system undergoes a diversity of structural, biochemical, and functional changes necessary for adaptation to air breathing at birth. The study aims to map pulmonary cell heterogeneity and dynamic gene expression changes driving adaptation to air breathing at birth using single‑cell RNA sequencing of mouse lungs on postnatal day 1. The authors employed an iterative, unbiased single‑cell RNA‑seq pipeline to classify diverse lung cell types and compared pre‑ and post‑birth transcriptomes to pinpoint cell‑type‑specific signaling pathways, such as stress and unfolded protein responses, involved in perinatal lung adaptation. They uncovered distinct epithelial, endothelial, mesenchymal, and immune cell populations with unique subpopulations, offering a single‑cell perspective on how the lung adapts to air breathing after birth.

Abstract

The respiratory system undergoes a diversity of structural, biochemical, and functional changes necessary for adaptation to air breathing at birth. To identify the heterogeneity of pulmonary cell types and dynamic changes in gene expression mediating adaptation to respiration, here we perform single cell RNA analyses of mouse lung on postnatal day 1. Using an iterative cell type identification strategy we unbiasedly identify the heterogeneity of murine pulmonary cell types. We identify distinct populations of epithelial, endothelial, mesenchymal, and immune cells, each containing distinct subpopulations. Furthermore we compare temporal changes in RNA expression patterns before and after birth to identify signaling pathways selectively activated in specific pulmonary cell types, including activation of cell stress and the unfolded protein response during perinatal adaptation of the lung. The present data provide a single cell view of the adaptation to air breathing after birth.