Deriving lung progenitors from patient-specificMEK pluripotent cells is usually a important step in producing differentiated lung epithelium for illness modeling and transplantation. By mimicking the signaling events that take place through mouse lung development, we generated murine lung progenitors inside a series of discrete measures. Definitive endoderm derived from mouse embryonic stem cells DNA Methyltransferase inhibitor solubility (ESCs) was converted into foregut endoderm, then into replicating Nkx2.1+ lung endoderm, and eventually into multipotent embryonic lung progenitor and airway progenitor cells. We demonstrated that precisely-timed BMP, FGF, and WNT signaling are expected for NKX2.1 induction. Mouse ESC-derived Nkx2.1+ progenitor cells formed respiratory epithelium (tracheospheres) when transplanted subcutaneously into mice. We then adapted this method to produce disease-specific lung progenitor cells from human Cystic Fibrosis induced pluripotent stem cells (iPSCs), creating a platform for dissecting human lung ailment. These disease-specific human lung progenitors formed respiratory epithelium when subcutaneously engrafted into immunodeficient mice.