RT Journal Article
SR Electronic
T1 <em>In vitro</em> induction and <em>in vivo</em> engraftment of lung bud tip progenitor cells derived from human pluripotent stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 108845
DO 10.1101/108845
A1 Alyssa J. Miller
A1 Melinda S. Nagy
A1 David R. Hill
A1 Yu-Hwai Tsai
A1 Yoshiro Aoki
A1 Briana R. Dye
A1 Alana M. Chin
A1 Sha Huang
A1 Michael A.H. Ferguson
A1 Felix Zhou
A1 Eric S. White
A1 Vibha Lama
A1 Jason R. Spence
YR 2017
UL http://biorxiv.org/content/early/2017/06/08/108845.abstract
AB Author Contributions AJM and JRS conceived the study. AJM, MSN, BRD, YHT, SH, MAHF, YA, AMC, and ESW conducted experiments. AJM, DRH, BRD, YHT, MAHF, SH, MSN, YA, AMC, FZ, VL and JRS analyzed and interpreted results. ESW also provided critical materials and reagents. AJM and JRS wrote the manuscript. All authors read, edited and approved the final content of the manuscript.Conflicts of Interest The authors have no conflicts to declare.AbbreviationsBMPBone Morphogenic ProteinFGFFibroblast Growth FactorRAAll-Trans Retinoic AcidHLOHuman Lung OrganoidIn the current study, we identified that FGF7, CHIR-99021 and RA maintained isolated mouse and human lung bud tip progenitor cells in a multipotent state in vitro, and induced the differentiation of 3-dimensional lung-like epithelium from human pluripotent stem cells (hPSCs). These hPSC-derived lung organoids were initially patterned, with airway-like interior domains and bud tip-like progenitor domains at the periphery. Bud tip-like domains could be isolated, expanded and maintained as a nearly homogeneous population by serial passaging. In situ hybridization, immunostaining and transcriptome-wide analysis showed that hPSC-derived bud tip progenitors were remarkably similar to human fetal bud tip progenitors. hPSC-derived bud tip progenitors retained multilineage differentiation capabilities in vitro, survived in vitro for over 16 weeks and could be easily frozen and thawed. Furthermore, hPSC-derived bud tip progenitors successfully engrafted into the proximal airways of immunocompromised NSG mouse lungs, where they began to express markers of mature proximal lung cells.