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dc.contributor.authorHannan, Nicken
dc.contributor.authorSampaziotis, Fotiosen
dc.contributor.authorSegeritz, Charis-Patriciaen
dc.contributor.authorHanley, Neil Aen
dc.contributor.authorVallier, Ludovicen
dc.date.accessioned2015-05-21T12:11:27Z
dc.date.available2015-05-21T12:11:27Z
dc.date.issued2015-04-15en
dc.identifier.citationHannan et al. Stem Cells and Development (2015) Vol. 24 Issue 14, pp. 1680-1690. doi:10.1089/scd.2014.0512.en
dc.identifier.issn1547-3287
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247901
dc.description.abstractCollectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an advantageous progenitor cell type that can be used to amplify large quantities of cells for regenerative medicine applications and can be derived from any human pluripotent stem cell line. Here, we further demonstrate the application of hFSCs by generating a near homogeneous population of early pulmonary endoderm cells coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that are representative of distal airway epithelium that express NKX2.1, GATA6, and cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC. This culture system can be applied to hFSCs carrying the CFTR mutation Δf508, enabling the development of an in vitro model for cystic fibrosis. This platform is compatible with drug screening and functional validations of small molecules, which can reverse the phenotype associated with CFTR mutation. This is the first demonstration that multipotent endoderm stem cells can differentiate not only into both liver and pancreatic cells but also into lung endoderm. Furthermore, our study establishes a new approach for the generation of functional lung cells that can be used for disease modeling as well as for drug screening and the study of lung development.
dc.description.sponsorshipThis work was funded by the ERC starting grant Relieve IMDs (L.V.), the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V., N.R.F.H.), and the Evelyn trust (N.R.F.H.). N.A.H. is a Wellcome Trust senior clinical fellow (WT088566, WT097820). F.S. has been funded by an ACT Clinical Research Training Fellowship and a joint Sparks-MRC Clinical Research Training Fellowship. C.-P.S. is funded by the Children's Liver Diseases Foundation.
dc.languageEnglishen
dc.language.isoenen
dc.publisherMary Ann Liebert Publishers
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjectLungen
dc.subjectEmbryonic Stem Cellsen
dc.subjectInduced Pluripotenten
dc.subjectPatterningen
dc.titleGeneration of Distal Airway Epithelium from Multipotent Human Foregut Stem Cellsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Mary Ann Liebert Publishers via http://dx.doi.org/10.1089/scd.2014.0512en
prism.endingPage1690
prism.publicationDate2015en
prism.publicationNameStem Cells and Developmenten
prism.startingPage1680
prism.volume24en
dc.rioxxterms.funderNIHR
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderMRC
dc.rioxxterms.projectidWT088566
rioxxterms.versionofrecord10.1089/scd.2014.0512en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-04-15en
dc.contributor.orcidVallier, Ludovic [0000-0002-3848-2602]
dc.identifier.eissn1557-8534
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/L016761/1)
pubs.funder-project-idMRC (G1000847)
pubs.funder-project-idMRC (G0800784)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales