In vitro study reveals a surface marker profile for isolating NKX2-1-expressing human lung progenitors from stem cells, highlighting new avenues for regenerative medicine.
Key Points
To isolate, purify, and characterize primordial human NKX2-1-expressing lung epithelial progenitors derived from pluripotent stem cells during early developmental specification.
Engineered NKX2-1GFP reporter human pluripotent stem cells (PSCs) and directed their in vitro differentiation to generate primordial lung progenitors.
Assessed progenitor differentiation capacity using defined mesenchymal-free 3D spheroid cultures and recombination with fetal mouse lung mesenchyme.
Profiled early lineage specification using real-time live imaging, time-series global transcriptomics, and single-cell RNA sequencing.
Purified NKX2-1+ progenitors demonstrated autonomous lung epithelial maturation, forming epithelial-only 3D spheroids without mesenchymal coculture support.
Transcriptomic and single-cell RNA sequencing uncovered conserved, stage-dependent gene expression signatures driving human lung lineage commitment.
Identified a CD47hiCD26lo cell surface marker signature that enables prospective sorting of primordial lung progenitors from untargeted, patient-specific PSC lines.