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.
Highlights
The respiratory system undergoes a diversity of structural, biochemical, and functional changes necessary for adaptation to air breathing at birth
Graph-based clustering strategy, we identified four major cell types and 20 cell sub-types from postnatal day 1 (PND1) mouse lung (Methods; Fig. 1a; Supplementary Figures 2–6; Supplementary Data 1)
We integrated scRNA-seq analysis of PND1 mouse lung with developmental RNA profiles obtained from whole lung tissue to begin to understand the complexity of cellular adaptation of the lung to air breathing at birth
Summary
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. 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. Despite the complexities of lung structure and the diversity of cells involved in lung maturation and adaptation, most genomic and proteomic data used bulk measurements from whole lung tissue to understand perinatal lung development, limiting insights into the activities of and interactions among individual cells[8,9,10,11]. Data from the present study are freely accessed at https://research.cchmc. org/pbge/lunggens/SCLAB.html
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