Mou, HongmeiZhao, RuiSherwood, RichardAhfeldt, TimLapey, AllenWain, John CharlesSicilian, LeonardIzvolsky, KonstantinLau, FrankMusunuru, KiranCowan, ChadRajagopal, Jayaraj2018-02-072012Mou, Hongmei, Rui Zhao, Richard Sherwood, Tim Ahfeldt, Allen Lapey, John Wain, Leonard Sicilian, et al. 2012. “Generation of Multipotent Lung and Airway Progenitors from Mouse ESCs and Patient-Specific Cystic Fibrosis iPSCs.” Cell Stem Cell 10 (4) (April): 385–397. doi:10.1016/j.stem.2012.01.018.1934-5909http://nrs.harvard.edu/urn-3:HUL.InstRepos:34795054Deriving lung progenitors from patient-specific pluripotent cells is a key step in producing differentiated lung epithelium for disease modeling and transplantation. By mimicking the signaling events that occur during mouse lung development, we generated murine lung progenitors in a series of discrete steps. Definitive endoderm derived from mouse embryonic stem cells (ESCs) was converted into foregut endoderm, then into replicating Nkx2.1+ lung endoderm, and finally into multipotent embryonic lung progenitor and airway progenitor cells. We demonstrated that precisely-timed BMP, FGF, and WNT signaling are required for NKX2.1 induction. Mouse ESC-derived Nkx2.1+ progenitor cells formed respiratory epithelium (tracheospheres) when transplanted subcutaneously into mice. We then adapted this strategy to produce disease-specific lung progenitor cells from human Cystic Fibrosis induced pluripotent stem cells (iPSCs), creating a platform for dissecting human lung disease. These disease-specific human lung progenitors formed respiratory epithelium when subcutaneously engrafted into immunodeficient mice.en-USJournal Article2014-02-24Chad Cowan10.1016/j.stem.2012.01.018