TY - JOUR T1 - Integrated growth factor signaling promotes lung epithelial progenitor cell expansion and maintenance in mice and humans JF - bioRxiv DO - 10.1101/108845 SP - 108845 AU - Alyssa J. Miller AU - Briana R. Dye AU - Melinda S. Nagy AU - Yu-Hwai Tsai AU - Sha Huang AU - Michael A.H. Ferguson AU - Jason R. Spence Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/15/108845.abstract N2 - 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.BMPBone Morphogenic ProteinFGFFibroblast Growth FactorRAAll-Trans Retinoic AcidHLOHuman Lung Organoid ER -