Generation of Multipotent Lung and Airway Progenitors from Mouse ESCs and Patient-Specific Cystic Fibrosis iPSCs
View/ Open
54303695.pdf (2.614Mb)
Access Status
Full text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.Author
Zhao, Rui
Sicilian, Leonard
Izvolsky, Konstantin
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1016/j.stem.2012.01.018Metadata
Show full item recordCitation
Mou, 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.Abstract
Deriving 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.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:34795054
Collections
- FAS Scholarly Articles [18295]
Contact administrator regarding this item (to report mistakes or request changes)