Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells

Stem Cells and Development
Nicholas R F HannanLudovic Vallier

Abstract

Collectively, 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. T...Continue Reading

References

Jan 8, 2004·Respirology : Official Journal of the Asian Pacific Society of Respirology·Darryl A Knight, Stephen T Holgate
Dec 2, 2005·The European Respiratory Journal·I A ForrestP A Corris
Apr 15, 2006·Development·Wellington V Cardoso, Jining Lü
Jun 6, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Samara L Lewis, Patrick P L Tam
Jun 30, 2006·Developmental Biology·Zengxin WangKaren Niederreither
Jan 24, 2007·Physiological Reviews·Yutaka MaedaJeffrey A Whitsett
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Dachun WangRick A Wetsel
Dec 15, 2007·BMJ : British Medical Journal·Jane C DaviesAndrew Bush
Aug 8, 2008·Proceedings of the American Thoracic Society·Emma L Rawlins
Aug 27, 2010·The Journal of Clinical Investigation·S Tamir RashidLudovic Vallier
Feb 16, 2011·Journal of Molecular Endocrinology·Henrik Fagman, Mikael Nilsson
Feb 22, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Emma L Rawlins
Oct 17, 2012·Paediatric Respiratory Reviews·Bradley S Quon, Moira L Aitken
Feb 22, 2013·Nature Protocols·Nicholas R F HannanLudovic Vallier
May 3, 2013·American Journal of Respiratory and Critical Care Medicine·Christopher H Goss, Felix Ratjen
Dec 3, 2013·Nature Biotechnology·Sarah X L HuangHans-Willem Snoeck
Dec 10, 2013·Stem Cell Reports·Nicholas R F HannanLudovic Vallier

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Citations

Jun 12, 2016·Developmental Biology·Megan Aurora, Jason R Spence
Sep 13, 2016·Diabetes, Obesity & Metabolism·A Grapin-Botton
Sep 23, 2016·Transplantation·Ignacio Anegon, Tuan Huy Nguyen
Apr 14, 2017·Physiology·Alyssa J Miller, Jason R Spence
Apr 30, 2016·Biomedical Engineering and Computational Biology·Dipasri KonarSean V Murphy
Jan 22, 2019·Nature Protocols·Alyssa J MillerJason R Spence
Jul 13, 2018·European Respiratory Review : an Official Journal of the European Respiratory Society·Dymph KlayColine H M van Moorsel
Sep 29, 2018·The European Respiratory Journal·Konstantinos GkatzisSaverio Bellusci
Mar 11, 2020·Frontiers in Cell and Developmental Biology·Yang PengNan-Shan Zhong
Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty

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Methods Mentioned

BETA
RECs
FACS
flow cytometry
enzyme-linked immunosorbent assay
Confocal microscopy

Software Mentioned

AxioVision
ImageJ
GraphPad Prism

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