Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells

Area of Science:

• Pulmonary medicine
• Stem cell biology
• Cellular and molecular biology

Background:

• Pulmonary neuroendocrine cells (PNECs) expansion is linked to various human lung diseases.
• Studying human PNECs is challenging due to their low abundance and difficult isolation.

Purpose of the Study:

• To develop a reliable method for generating human pulmonary neuroendocrine cells (PNECs) for research.
• To create a scalable model system for investigating lung diseases associated with PNEC abnormalities.

Main Methods:

• Generation of induced pulmonary neuroendocrine cells (iPNECs) from induced pluripotent stem cells (iPSCs).
• Optimization of differentiation using an air-liquid interface and Notch signaling inhibition.
• Single-cell RNA sequencing (scRNA-seq) for gene expression profiling and cell lineage analysis.

Main Results:

• Generated iPNECs express key PNEC markers and secrete neuropeptides, mimicking primary PNECs.
• Differentiation efficiency was enhanced by air-liquid interface culture and Notch inhibition.
• scRNA-seq confirmed gene expression concordance with human fetal PNECs and suggested a basal cell origin.

Conclusions:

• Induced pluripotent stem cells can be differentiated into functional iPNECs.
• This iPNEC model offers a sustainable and scalable source for studying lung diseases.
• The model facilitates research into pulmonary neuroendocrine cell pathophysiology in various lung conditions.