Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate

• DOI: 10.1073/pnas.1719474115
• Publication Date: 2018-02-20T19:31:23Z
• Authors: Yanjie Wang; Zan Tang; Huanwei Huang; Jiao Li; Zheng Wang; Yuanyuan Yu; Chengwei Zhang; Juan Li; Huaping Dai; Fengchao Wang; Tao Cai; Nan Tang
• Keywords: 0301 basic medicine; Igfbp2; pulmonary alveolar type I cells; 1.1 Normal biological development and functioning; 610; Mice, Transgenic; Regenerative Medicine; Transgenic; Mice; 03 medical and health sciences; lineage tracing; Underpinning research; single cell RNA-seq; Animals; Regeneration; Cell Lineage; Lung; alveolar development and regeneration; Biomedical and Clinical Sciences; Sequence Analysis, RNA; 600; Cell Differentiation; Biological Sciences; Pulmonary Alveoli; Insulin-Like Growth Factor Binding Protein 2; Alveolar Epithelial Cells; RNA; Biochemistry and Cell Biology; Single-Cell Analysis; Transcriptome; Sequence Analysis

Significance

Pulmonary alveolar type I (AT1) cells are essential for the gas-exchange function of lungs. AT1 cells retain their cellular plasticity during injury-induced alveolar regeneration. However, we know very little about the developmental heterogeneity of the AT1 cell population. Our study identified a robust genetic marker of postnatal AT1 cells, insulin-like growth factor-binding protein 2 (Igfbp2). We use this marker to demonstrate that the postnatal AT1 cell population actually consists of two AT1 cell subtypes (Hopx + Igfbp2 + and Hopx + Igfbp2 − AT1 cells) with distinct cell fates during alveolar regeneration. The large majority of adult AT1 cells expresses Igfbp2 and cannot transdifferentiate into AT2 cells during post pneumonectomy formation of new alveoli. Therefore, Hopx + Igfbp2 + AT1 cells represent the terminally differentiated population of AT1 cells.