Generation and expansion of induced respiratory airway progenitors (iRAPs) from human pluripotent stem cells.
Several novel distal lung populations were recently identified that may be involved in regeneration after injury.1–3 As these are absent in rodents, a deeper understanding of their roles and lineage relations requires availability of equivalent cells in vitro. Here we report the generation of expandable, clonal spheres, called induced respiratory airway progenitors (iRAPs), from human pluripotent stem cells. iRAPs consist mainly of previously identified type 0 alveolar epithelial (AT0) cells, terminal respiratory bronchiole stem cells (TRB-SCs) and distal basal cells (BCs).3 Velocity analysis of single cell RNAseq data suggests that distal BCs are the most undifferentiated progenitors in the iRAPs and give rise to AT0 cells. iRAPs will be an important resource for studies in human lung regeneration, and potentially for regenerative approaches for human lung disease. Overall design: We performed single cell RNA sequencing on induced respiratory airway progenitors. iRAPs were dissociated to single cells and resuspended at a concentration of 5000 cells/ul for sequencing.