Interrupted reprogramming of Alveolar Type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis

We describe here an interrupted reprogramming strategy to generate "induced Progenitor-Like (iPL) cells" from Alveolar Epithelial Type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc; OSKM) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state. Microarray analysis of genome-wide transcriptional changes showed the ability of AEC-II-iPL cells to return to the original phenotype Day0 freshly isolated AEC-II cells, cells were cultured for 2 weeks without Dox (2WND), followed by 2-week dox treamtent (2WND+2W+D, AEC-II-iPL cells), AEC-II-iPL cells with subsequent 2-week culture in Dox-free media (2WND+2W+D+2w-D), and iPS cells were collected for RNA extraction and hybridization on Affymetrix microarrays.