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Efficient generation of lung and airway epithelial cells from human pluripotent stem cells

Nature Biotechnology volume 32, pages 84–91 (2014)Cite this article

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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.

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Figure 1: Establishment of a protocol of lung field induction.
Figure 2: Requirement of morphogens for lung field induction from hPSCs.
Figure 3: In vivo potential of hPSC-derived lung and airway progenitors.
Figure 4: Further differentiation of hPSC-derived lung and airway progenitors.
Figure 5: Terminal differentiation of hPSCS-derived lung and airway progenitors.
Figure 6: Morphology and function of hPSC-derived lung and airway epithelium.

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Acknowledgements

S.X.L.H. is a Druckenmiller Fellow of the New York Stem Cell Foundation. The authors wish to thank J. Sonnet and the Columbia Lung Regeneration Team, D. Farber and J. Thome for providing samples of human lung tissue; K. Brown for kind help with electron microscopy; S.-H. Ho for assistance with microscopy.

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Authors and Affiliations

  1. Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA

    Sarah X L Huang, Zheng Hu, Yong-Guang Yang, Ya-Wen Chen, Melanie Mumau, Michael D Green & Hans-Willem Snoeck

  2. Department of Medicine, Columbia University Medical Center, New York, New York, USA

    Sarah X L Huang, Mohammad Naimul Islam, Yong-Guang Yang, Ya-Wen Chen, Melanie Mumau, Gordana Vunjak-Novakovic, Jahar Bhattacharya & Hans-Willem Snoeck

  3. Department of Biomedical Engineering, Columbia University, New York, New York, USA

    John O'Neill & Gordana Vunjak-Novakovic

  4. Department of Physiology & Cellular Biophysics, Columbia University Medical Center, New York, New York, USA

    Jahar Bhattacharya

  5. Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA

    Hans-Willem Snoeck

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Contributions

S.X.L.H. performed most experiments, developed this protocol and co-wrote the manuscript; M.N.I. performed functional analysis of ATII cells supervised by J.B.; M.M., M.D.G. and Y.-W.C. gave technical advice and assisted S.X.L.H. experimentally; Z.H. performed kidney capsule transplantations supervised by Y.-G.Y.; J.O.N. provided human lung human decellularized extracellular lung matrix and these experiments were supervised by G.V.-N.; H.-W.S. developed the concept, co-analyzed primary data and co-wrote the manuscript with S.X.L.H.

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Correspondence to Hans-Willem Snoeck.

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The authors have filed patent application IRCU13340.

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Huang, S., Islam, M., O'Neill, J. et al. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol 32, 84–91 (2014). https://doi.org/10.1038/nbt.2754

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