Efficient generation and transcriptomic profiling of human iPSC-derived pulmonary neuroendocrine cells

Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (<1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem cells (iPSCs) to generate induced PNECs (iPNECs) which express core PNEC markers, genes therby recapitulating known functions of primary PNECs. Single-cell RNA sequencing (scRNA-seq) of these iPNEC revealed a PNEC-associated gene expression profile that is concordant between iPNECs and human fetal PNECs. In conclusion, our model has the potential to provide an unlimited source of human iPNECs to explore PNEC pathophysiology associated with several lung diseases. Overall design: Examination of 2 iPSC replicates for their differentiation to iPNEC.