title: Efficient generation of lung and airway epithelial cells from human pluripotent stem cells.
abstract: The ability to generate lung and airway epithelial cells from human pluripotent stem cells (hPSCs) would have applications in regenerative medicine, modeling of lung disease, drug screening and studies of human lung development. We have established, based on developmental paradigms, a highly efficient method for directed differentiation of hPSCs into lung and airway epithelial cells. Long-term differentiation of hPSCs in vivo and in vitro yielded basal, goblet, Clara, ciliated, type I and type II alveolar epithelial cells. The type II alveolar epithelial cells were capable of surfactant protein-B uptake and stimulated surfactant release, providing evidence of specific function. Inhibiting or removing retinoic acid, Wnt and BMP-agonists to signaling pathways critical for early lung development in the mouse-recapitulated defects in corresponding genetic mouse knockouts. As this protocol generates most cell types of the respiratory system, it may be useful for deriving patient-specific therapeutic cells.
authors.affiliation: 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA. [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Sarah X L
authors.initials: SX
authors.lastname: Huang
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Mohammad Naimul
authors.initials: MN
authors.lastname: Islam
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA. [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
authors.affiliation: 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA. [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA. [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Mumau
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Green
authors.affiliation: 1] Department of Medicine, Columbia University Medical Center, New York, New York, USA. [2] Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
authors.affiliation: 1] Department of Medicine, Columbia University Medical Center, New York, New York, USA. [2] Department of Physiology & Cellular Biophysics, Columbia University Medical Center, New York, New York, USA.
authors.forename: Jahar
authors.initials: J
authors.lastname: Bhattacharya
authors.affiliation: 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA. [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA. [3] Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Hans-Willem
authors.initials: HW
authors.lastname: Snoeck
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D011498:Protein Precursors / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D011498:Protein Precursors; D011510:Proteolipids; C105511:surfactant protein B propeptide; D014212:Tretinoin