Summary
During lung branching morphogenesis, a multipotent progenitor population resides at the tips of bifurcating epithelial tubes that give rise to all lung epithelial cell types (1). Previously (2,3), we demonstrated that human pluripotent stem cells (hPSCs) could differentiate into human lung organoids (HLOs), which possessed airway-like structures and alveolar cells, but it was unclear if HLOs possessed a bona fide tip-progenitor population. The goal of the current study was to understand how tip-progenitors are regulated such that this population could be induced in HLO cultures. Using isolated embryonic mouse and human fetal tip-progenitors, we identified factors that promoted long-term growth and maintenance of this population in vitro. Our results showed significant functional and expression differences between mouse and human tip-progenitors, and demonstrated de novo induction of a robust population of budding, SOX9+ progenitor-like cells in HLOs.
- BMP
- Bone Morphogenic Protein
- FGF
- Fibroblast Growth Factor
- RA
- All-Trans Retinoic Acid
- HLO
- Human Lung Organoid
Footnotes
Conflicts of Interest: The authors have no conflicts to declare.