Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, approximately 20-30% of NKX2.1+ (or thyroid transcription factor 1+ (TTF1+)) cells did not co-localize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1+ cells co-expressed either pro-SP-C or the AT1 cell marker HOPX. Not all HOPX+ cells co-localize with the AT1 cell marker aquaporin 5 (AQP5) and some AQP5+ cells were NKX2.1+. HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C co-localize in AT2 cells, NKX2.1 and HOPX or AQP5 co-localize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung.
- Intermediate cells
- Alveolar epithelial type I cell
- Alveolar epithelial type II cell
- Copyright © 2015, American Journal of Physiology - Lung Cellular and Molecular Physiology