RT Journal Article
SR Electronic
T1 Integrated growth factor signaling promotes lung epithelial progenitor cell expansion and maintenance in mice and humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 108845
DO 10.1101/108845
A1 Alyssa J. Miller
A1 Briana R. Dye
A1 Melinda S. Nagy
A1 Yu-Hwai Tsai
A1 Sha Huang
A1 Michael A.H. Ferguson
A1 Jason R. Spence
YR 2017
UL http://biorxiv.org/content/early/2017/02/15/108845.abstract
AB 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